<?xml version="1.0" encoding="UTF-8"?><rss version="2.0" xmlns:content="http://purl.org/rss/1.0/modules/content/" xmlns:wfw="http://wellformedweb.org/CommentAPI/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:atom="http://www.w3.org/2005/Atom" xmlns:sy="http://purl.org/rss/1.0/modules/syndication/" xmlns:slash="http://purl.org/rss/1.0/modules/slash/" > <channel> <title>Food and Drug Administration – Policy & Medicine</title> <atom:link href="https://www.policymed.com/tag/food-and-drug-administration/feed" rel="self" type="application/rss+xml" /> <link>https://www.policymed.com</link> <description>Legal, Regulatory, and Compliance Issues</description> <lastBuildDate>Sat, 30 Nov 2024 23:54:21 +0000</lastBuildDate> <language>en-US</language> <sy:updatePeriod> hourly </sy:updatePeriod> <sy:updateFrequency> 1 </sy:updateFrequency> <image> <url>https://www.policymed.com/wp-content/uploads/2018/05/cropped-favicon-32x32.png</url> <title>Food and Drug Administration – Policy & Medicine</title> <link>https://www.policymed.com</link> <width>32</width> <height>32</height> </image> <item> <title>Industry Wants Greater Transparency in FDA Meeting Decisions</title> <link>https://www.policymed.com/2024/12/industry-wants-greater-transparency-in-fda-meeting-decisions.html</link> <comments>https://www.policymed.com/2024/12/industry-wants-greater-transparency-in-fda-meeting-decisions.html#respond</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Tue, 24 Dec 2024 09:26:19 +0000</pubDate> <category><![CDATA[FDA]]></category> <category><![CDATA[Transparency]]></category> <category><![CDATA[Artificial Intelligence]]></category> <category><![CDATA[BIO]]></category> <category><![CDATA[Biopharmaceutical Products]]></category> <category><![CDATA[Biotechnology Innovation Organization]]></category> <category><![CDATA[Clinical Development]]></category> <category><![CDATA[Drug Approval Process]]></category> <category><![CDATA[Drug development]]></category> <category><![CDATA[Drug Industry]]></category> <category><![CDATA[Drug Sponsors]]></category> <category><![CDATA[FDA Commitments]]></category> <category><![CDATA[FDA Performance]]></category> <category><![CDATA[FDA Stakeholder Comments]]></category> <category><![CDATA[FDA-Sponsor Interactions]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[In-person Meetings]]></category> <category><![CDATA[Meeting Agendas]]></category> <category><![CDATA[Meeting Background Packages]]></category> <category><![CDATA[Meeting Best Practices]]></category> <category><![CDATA[Meeting Management]]></category> <category><![CDATA[Meeting Minutes]]></category> <category><![CDATA[Meeting Scheduling]]></category> <category><![CDATA[PDUFA Goals]]></category> <category><![CDATA[PDUFA VII]]></category> <category><![CDATA[PhRMA]]></category> <category><![CDATA[Prescription Drug User Fee Act]]></category> <category><![CDATA[Regulatory Delays]]></category> <category><![CDATA[Regulatory Review]]></category> <category><![CDATA[Regulatory Uncertainty]]></category> <category><![CDATA[Virtual Meetings]]></category> <category><![CDATA[Written Response Only Letters]]></category> <category><![CDATA[WRO Letters]]></category> <guid isPermaLink="false">https://www.policymed.com/?p=17223</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="1200" height="800" src="https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" fetchpriority="high" srcset="https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60.jpg 1200w, https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60-300x200.jpg 300w, https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60-1024x683.jpg 1024w, https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60-768x512.jpg 768w, https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60-450x300.jpg 450w" sizes="(max-width: 1200px) 100vw, 1200px" /></div>Earlier this year, the United States Food and Drug Administration (FDA) sought comments on the best practices for meeting management, holding a workshop to fulfill a commitment in the Prescription Drug User Fee Act (PDUFA VII). In the workshop, FDA aimed to understand issues related to meeting requests, efficient time management, finalizing meeting agenda, development […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="1200" height="800" src="https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" srcset="https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60.jpg 1200w, https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60-300x200.jpg 300w, https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60-1024x683.jpg 1024w, https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60-768x512.jpg 768w, https://www.policymed.com/wp-content/uploads/2022/10/stencil.default-60-450x300.jpg 450w" sizes="(max-width: 1200px) 100vw, 1200px" /></div><p>Earlier this year, the United States Food and Drug Administration (FDA) <a href="https://www.regulations.gov/document/FDA-2024-N-2561-0001">sought comments</a> on the best practices for meeting management, holding a workshop to fulfill a commitment in the Prescription Drug User Fee Act (PDUFA VII). In the workshop, FDA aimed to understand issues related to meeting requests, efficient time management, finalizing meeting agenda, development and submission of meeting background packages, and lessons learned from the use of virtual meeting platforms during the COVID-19 pandemic.</p> <p>The meeting was held in person and virtually on July 22, 2024, with electronic or written comments due to the FDA no later than August 22, 2024. Several industry stakeholders took the opportunity to submit written comments on the issues, including <a href="https://www.regulations.gov/comment/FDA-2024-N-2561-0007">PhRMA</a> and the <a href="https://www.regulations.gov/comment/FDA-2024-N-2561-0006">Biotechnology Innovation Organization (BIO)</a>.</p> <p>In its comments, PhRMA noted that “[m]eetings with the FDA during the drug development and regulatory review processes are extremely valuable to sponsors and provide a venue and opportunity to receive substantive feedback to help reduce regulatory uncertainty, which is critical for the development of innovative biopharmaceutical products.” The comment goes on to note that delays in scheduling meetings or receiving input from the Agency can slow or alter development times, which may impact the ultimate patient access to new medicines and treatments. PhRMA noted that “over the last several years, FDA has consistently missed negotiated PDUFA performance goals for key meeting management metrics.”</p> <p>BIO also took issue with FDA’s performance, citing FDA’s own FY2023 PDUFA performance report that found it failed to meet 9 out of 14 meeting-related commitments in FY 2022. “Given the criticality of these interactions, this level of performance may have a deleterious impact on FDA’s and industry’s shared goals of expeditiously developing and providing novel, safe, and effective therapies for patients. Establishing and implementing best practices for both industry and the agency would improve the planning and conduct of FDA/sponsor interactions, potentially improving performance against PDUFA goals.”</p> <p>PhRMA and BIO both stated their belief that there is a need for both in-person and virtual meetings regarding written response only (WRO) letters, saying sponsors often prefer direct communication with the agency to get quick responses, but are often denied such meetings and instead given WRO letters, which tends to slow down the process. PhRMA referenced statistics that showed that more than half of the interactions between FDA and sponsors through WRO letters involve clarifying questions, questions that could have been answered during an in-person or virtual meeting. BIO asked FDA to require staff provide sponsors a rationale when denying direct meetings and issuing WRO letters instead.</p> <p>For all face-to-face meetings, BIO commented that FDA and sponsors should agree to keep meeting minutes that summarize their discussions. This would help confirm agreements, minimize communication discrepancies, and ensure mutual understanding. BIO suggested that technology such as artificial intelligence could be to maintain the minutes to make the process expeditious and efficient.</p> <p>In its comments, PhRMA asked that standard meeting management best practices be adopted, including designating an FDA representative whose role will be to keep all sides focused on the agenda during meetings. Additionally, all participants should ensure that the right people are attending the meeting. To that end, “PhRMA requests that FDA proactively provide the current titles of all attendees, their function – for example, lead CMC reviewer – and the role they play in the meeting (e.g., decision-makers or observers.” said PhRMA. PhRMA believes this information should be automatically provided, instead of the current practice, which is that sponsors must request the information after receiving the list of attendees, or otherwise “independently ascertain this information.”</p> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2024/12/industry-wants-greater-transparency-in-fda-meeting-decisions.html/feed</wfw:commentRss> <slash:comments>0</slash:comments> </item> <item> <title>FDA Seeks Comments on Transparency and Communication for New Entities</title> <link>https://www.policymed.com/2012/07/fda-seeks-comments-on-transparency-and-communication-for-new-entities.html</link> <comments>https://www.policymed.com/2012/07/fda-seeks-comments-on-transparency-and-communication-for-new-entities.html#respond</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Mon, 23 Jul 2012 00:46:00 +0000</pubDate> <category><![CDATA[FDA]]></category> <category><![CDATA[Congress]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[NEW]]></category> <category><![CDATA[New Drug Application]]></category> <category><![CDATA[PDUFA]]></category> <category><![CDATA[Prescription Drug User Fee Act]]></category> <category><![CDATA[United States]]></category> <category><![CDATA[United States Congress]]></category> <guid isPermaLink="false">http://www.policymed.com/fda-seeks-comments-on-transparency-and-communication-for-new-entities/</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="452" height="134" src="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb8834017616822270970c-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" srcset="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb8834017616822270970c-800wi.jpg 452w, https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb8834017616822270970c-800wi-300x89.jpg 300w" sizes="(max-width: 452px) 100vw, 452px" /></div>The Food and Drug Administration (FDA) recently announced an opportunity for public comment on the statement of work for an assessment of the Program for Enhanced Review Transparency and Communication for New Molecular Entity (NME) New Drug Applications (NDAs) and Original Biologics License Applications (BLAs) (the Program). The Program is part of the FDA performance […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="452" height="134" src="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb8834017616822270970c-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb8834017616822270970c-800wi.jpg 452w, https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb8834017616822270970c-800wi-300x89.jpg 300w" sizes="auto, (max-width: 452px) 100vw, 452px" /></div><p><span style="font-family: arial,helvetica,sans-serif;">The <a class="zem_slink" title="Food and Drug Administration" href="http://maps.google.com/maps?ll=39.0353363,-76.9830894&spn=0.01,0.01&q=39.0353363,-76.9830894 (Food%20and%20Drug%20Administration)&t=h" target="_blank" rel="geolocation noopener">Food and Drug Administration (FDA)</a> <a href="http://www.regulations.gov/#!docketDetail;dct=FR%252BPR%252BN%252BO%252BSR;rpp=25;po=0;D=FDA-2012-N-0603">recently announced</a> an opportunity for <a class="zem_slink" title="Public comment" href="http://en.wikipedia.org/wiki/Public_comment" target="_blank" rel="noopener wikipedia">public comment</a> on the statement of work for an <a href="http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm304793.pdf.">assessment</a> of the Program for Enhanced Review Transparency and Communication for New Molecular Entity (<a class="zem_slink" title="NME" href="http://www.nme.com/" target="_blank" rel="homepage noopener">NME</a>) <a class="zem_slink" title="New Drug Application" href="http://en.wikipedia.org/wiki/New_Drug_Application" target="_blank" rel="noopener wikipedia">New Drug Applications</a> (NDAs) and Original Biologics License Applications (BLAs) (the Program). The Program is part of the FDA performance commitments under the fifth authorization of the <a class="zem_slink" title="Prescription Drug User Fee Act" href="http://en.wikipedia.org/wiki/Prescription_Drug_User_Fee_Act" target="_blank" rel="noopener wikipedia">Prescription Drug User Fee Act</a> (PDUFA), which, allows FDA to collect user fees for the review of human drug and <a class="zem_slink" title="Biologic" href="http://en.wikipedia.org/wiki/Biologic" target="_blank" rel="noopener wikipedia">biologics</a> applications for fiscal years (FYs) 2013–2017. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The Program will be evaluated by an independent contractor in an interim and final assessment. As part of the FDA performance commitment, FDA is providing a period of 30 days for public comment on the statement of work before letting the contract for the assessment. Comments are due by August 6, 2012: <strong>Docket No. FDA–2012–N–0603</strong>.<strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Background</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The timely review of the safety and effectiveness of new drugs and biologics is central to FDA’s mission to protect and promote the public health. Before the enactment of PDUFA in 1992, FDA’s drug review process was relatively slow and not very predictable compared to other countries. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">As a result of concerns expressed by industry, patients, and other stakeholders at the time, <a class="zem_slink" title="United States Congress" href="http://www.house.gov/" target="_blank" rel="homepage noopener">Congress</a> enacted PDUFA, which provided the added funds through user fees that enabled FDA to hire additional reviewers and support staff and upgrade its <a class="zem_slink" title="it training" href="http://www.infosecinstitute.com/" target="_blank" rel="infosec noopener">information technology systems</a>. In return for these additional resources, FDA agreed to certain review performance goals, such as completing reviews of NDAs and BLAs and taking regulatory actions on them in predictable timeframes. These changes revolutionized the <a class="zem_slink" title="Approved drug" href="http://en.wikipedia.org/wiki/Approved_drug" target="_blank" rel="noopener wikipedia">drug approval</a> process in the <a class="zem_slink" title="United States" href="http://maps.google.com/maps?ll=38.8833333333,-77.0166666667&spn=10.0,10.0&q=38.8833333333,-77.0166666667 (United%20States)&t=h" target="_blank" rel="geolocation noopener">United States</a> and enabled FDA to speed the application review process for new drugs and biologics without compromising the Agency’s high standards for demonstration of safety, efficacy, and quality of new drugs and biologics prior to approval. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">PDUFA provides FDA with a source of stable, consistent funding that has made possible our efforts to focus on promoting innovative therapies and helping to bring to market critical products for patients. When PDUFA was originally authorized in 1992, it had a 5-year term. The PDUFA program has been reauthorized every 5 years, with the most recent reauthorization occurring in 2012 for FYs 2013–2017. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">As directed by Congress in preparing for reauthorization of PDUFA for a new 5-year period, FDA conducted negotiations with regulated industry and conducted regular consultations with public stakeholders, including patient advocates, consumer advocates, and health care professionals between July 2010 and May 2011. Following these discussions, related public meetings, and Agency requests for public comment, FDA transmitted proposed PDUFA V recommendations to Congress for FYs 2013–2017 on January 13, 2012. FDA’s proposed PDUFA V recommendations included an FDA commitment to implement a new review program for NME NDAs and original BLAs to enhance review transparency and communication between FDA and applicants on these complex applications.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>II. PDUFA V NME NDA and Original BLA Review Program</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">FDA’s existing review performance goals for priority and standard applications, 6 and 10 months respectively, were established more than 15 years ago. Since that time, additional requirements in the drug review process and scientific advances in drug development have made those goals increasingly challenging to meet, particularly for more complex applications like NME NDAs and original BLAs that generally are discussed in an FDA advisory committee meeting. FDA further recognizes that increasing communication between the Agency and applicants during FDA’s review has the potential to increase efficiency in the review process. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">To promote greater transparency and improve communication between the FDA review team and the applicant, FDA has proposed a new review model for NME NDAs and original BLAs in PDUFA V. The Program provides opportunities for increased communication by building in mid-cycle communications and late-cycle meetings between FDA and applicants. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">To accommodate this increased interaction during regulatory review and to address the need for additional time to review these complex applications, FDA’s review clock will begin after the 60-day administrative filing review period for applications reviewed under the Program. The Program will apply to all NME NDAs and original BLAs received from October 1, 2012, through September 30, 2017. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The goal of the Program is to improve the efficiency and effectiveness of the first-cycle review process by increasing communication with sponsors before application submission to improve the quality and completeness of submissions, and by increasing communications during application review. This will provide sponsors with opportunities to clarify previous submissions and provide additional data and analyses that are readily available, potentially avoiding the need for an additional review cycle when FDA’s concerns about an application can be promptly resolved, but without compromising FDA’s traditional high standards for approval. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">An efficient and effective review process that allows for timely responses to FDA questions can help ensure timely patient access to safe, effective, and high quality new drugs and biologics. To understand the Program’s effect on the review of these applications, interim and final assessments by an independent contractor are key components of the Program. The performance commitments state that the statement of work for this effort will be published for public comment before beginning the assessment. Because the assessment needs to commence at the beginning of PDUFA V on October 1, 2012, FDA must publish the statement of work for public comment in advance of that reauthorization to be able to begin the assessment on October 1, 2012. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Key Objectives</strong><strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The primary objective of this evaluation task order is to determine the impact of the Program on the efficiency and effectiveness of review of NME NDAs and original BLAs. For an application that otherwise meets FDA’s high standards for approval, an optimal review allows for resolution of all issues (e.g., negotiation of labeling, risk evaluation and mitigation strategies (REMS) and postmarketing requirements and/or commitments) that must precede the issuance of an approval action letter on or before the original PDUFA goal date. Subsequent review cycles are sometimes necessary for applications that contain outstanding deficiencies or require additional discussions between FDA and the applicant. This represents an inefficient use of resources if resolution of these issues could have been achieved prior to the first cycle PDUFA goal date. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The Program builds in specific opportunities for communication between FDA and the applicant regarding the content of a complete application prior to submission and any deficiencies identified during application review while also building in additional time during review to address any deficiencies that can be resolved prior to the first cycle PDUFA goal date. Despite these modifications to the review process, the first review cycle alone may be unable to accommodate substantial application deficiencies or a delay in an applicant’s response to an The primary objective of this evaluation task order is to determine the impact of the Program on the efficiency and effectiveness of review of NME NDAs and original BLAs. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">For an application that otherwise meets FDA’s high standards for approval, an optimal review allows for resolution of all issues (e.g., negotiation of labeling, risk evaluation and mitigation strategies (REMS) and postmarketing requirements and/or commitments) that must precede the issuance of an approval action letter on or before the original PDUFA goal date. Subsequent review cycles are sometimes necessary for applications that contain outstanding deficiencies or require additional discussions between FDA and the applicant. This represents an inefficient use of resources if resolution of these issues could have been achieved prior to the first cycle PDUFA goal date. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The Program builds in specific opportunities for communication between FDA and the applicant regarding the content of a complete application prior to submission and any deficiencies identified during application review while also building in additional time during review to address any deficiencies that can be resolved prior to the first cycle PDUFA goal date. Despite these modifications to the review process, the first review cycle alone may be unable to accommodate substantial application deficiencies or a delay in an applicant’s response to an information request that could address the identified deficiencies. Therefore, it will be important for the program assessment to examine attributes beyond those of the Program in assessing the review performance for these applications. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Because the features of the Program occur throughout the review cycle, the assessment shall be performed while these applications are under FDA review and finalized soon after the review is completed. This prospective analysis will examine the set of metrics described in the PDUFA V commitment letter in addition to the attributes of the applications and the review process that factored into the timing of the regulatory outcome of the application. Key Objectives of the Assessment include: </span></p> <ol> <li><span style="font-family: arial,helvetica,sans-serif;">Using information from FDA’s corporate databases, construct and analyze a baseline data set of NME NDAs and original BLAs received and acted on prior to implementation of the Program. This set of applications shall be used to assess the impact on the key evaluation measures for applications reviewed under the Program. </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Using information from FDA’s corporate databases as well as other databases (e.g., database or other tracking mechanism developed by contractor) for applications reviewed under the Program, collect and analyze data on all NME NDA and original BLAs reviewed under the Program. </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Determine the nature of relationships between attributes of the Program and the timing of the regulatory outcome in the first review cycle </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Determine the nature of relationships between other attributes of the review process and applications that are reviewed under the Program and the timing of the regulatory outcome in the first review cycle. </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Collect and analyze applicant and FDA review staff feedback on applications reviewed under the Program, including any best practices, key concerns, or challenges with regard to the enhanced communication and review of these applications. </span></li> </ol> <div class="zemanta-pixie" style="margin-top: 10px; height: 15px;"><a class="zemanta-pixie-a" title="Enhanced by Zemanta" href="http://www.zemanta.com/?px"><img decoding="async" class="zemanta-pixie-img" style="float: right;" src="http://img.zemanta.com/zemified_e.png?x-id=9b5c3aee-620e-41e2-a972-818608471a69" alt="Enhanced by Zemanta" /></a></div> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2012/07/fda-seeks-comments-on-transparency-and-communication-for-new-entities.html/feed</wfw:commentRss> <slash:comments>0</slash:comments> </item> <item> <title>FDA: Recently Signed PDUFA 5 Provisions to Address Drug Shortages</title> <link>https://www.policymed.com/2012/07/fda-recently-signed-pdufa-5-provisions-to-address-drug-shortages.html</link> <comments>https://www.policymed.com/2012/07/fda-recently-signed-pdufa-5-provisions-to-address-drug-shortages.html#comments</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Wed, 18 Jul 2012 00:35:00 +0000</pubDate> <category><![CDATA[Drug Shortages]]></category> <category><![CDATA[FDA]]></category> <category><![CDATA[Arnold & Porter]]></category> <category><![CDATA[Center for Biologics Evaluation and Research]]></category> <category><![CDATA[FDA Commissioner Margaret Hamburg]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[Generic drug]]></category> <category><![CDATA[Margaret Hamburg]]></category> <category><![CDATA[NEW]]></category> <category><![CDATA[Prescription Drug User Fee Act]]></category> <guid isPermaLink="false">http://www.policymed.com/fda-recently-signed-pdufa-5-provisions-to-address-drug-shortages/</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="107" height="129" src="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb8834017743674d61970d-800wi.png" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" /></div>On July 9, 2012, President Obama signed into law the Food and Drug Administration Safety and Innovation Act (FDASIA), which gives FDA the authority to collect user fees from industry to fund reviews of innovator drugs, medical devices, generic drugs and biosimilar biologics. It also reauthorizes two programs that encourage pediatric drug development. “Support for […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="107" height="129" src="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb8834017743674d61970d-800wi.png" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" /></div><p><span style="font-family: arial,helvetica,sans-serif;">On July 9, 2012, President Obama signed into law the <a href="http://www.typepad.com/site/blogs/6a00e5520572bb883400e5520572c88834/post/Food%20and%20Drug%20Administration%20Safety%20and%20Innovation%20Act%20(FDASIA)">Food and Drug Administration Safety and Innovation Act</a> (FDASIA), which gives FDA the authority to collect user fees from industry to fund reviews of innovator drugs, medical devices, <a class="zem_slink" title="Generic drug" href="http://en.wikipedia.org/wiki/Generic_drug" target="_blank" rel="noopener wikipedia">generic drugs</a> and biosimilar biologics. It also reauthorizes two programs that encourage pediatric <a class="zem_slink" title="Drug development" href="http://en.wikipedia.org/wiki/Drug_development" target="_blank" rel="noopener wikipedia">drug development</a>. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">“Support for FDA user fees is a testament to the important role FDA plays in America’s healthcare continuum. FDA’s medical product decisions sit at the intersection of public health, innovation, and commerce and touch the lives of nearly every American every day,” said FDA Commissioner <a class="zem_slink" title="Margaret Hamburg" href="http://en.wikipedia.org/wiki/Margaret_Hamburg" target="_blank" rel="noopener wikipedia">Margaret A. Hamburg</a>, M.D. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">This is the fifth reauthorization of the <a class="zem_slink" title="Prescription Drug User Fee Act" href="http://en.wikipedia.org/wiki/Prescription_Drug_User_Fee_Act" target="_blank" rel="noopener wikipedia">Prescription Drug User Fee Act</a> or PDUFA, first enacted in 1992, and the third reauthorization of the Medical Device User Fee Act, or MDUFA, first enacted in 2002. Both programs have provided steady and reliable funding to maintain and support a staff of trained reviewers who must determine whether a proposed new product is safe and effective for patients and do so within a certain time period. The new user fee programs for generic drugs and biosimilar biologics build on the successes of these two established user fee programs. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">One of the most important provisions in FDASIA is Title X, which addresses the issues associated with drug shortages. A recent <a href="http://www.arnoldporter.com/resources/documents/A%20Reference%20Guide%20to%20the%20FDA%20Safety%20%20Innovation%20Act%20%28Updated%207-11-12%20at%201%2031PM%29.pdf">reference guide</a> published by the law firm <a href="http://www.arnoldporter.com/">Arnold & Porter, LLP</a>, provides in depth analysis of FDASIA, including Title X. Many of the provisions that made it into the final bill remained the same from the initial drug shortage legislation that was <a href="http://www.policymed.com/2012/04/fda-pfufa-senate-introduces-bi-partisan-legislation-on-drug-shortages-and-fast-track-product-approvals-and-other-issues.html">proposed back in April</a>. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">As we have noted several times over the last year, the number of drug shortages has been rising steadily over the last five years, nearly tripling from 61 in 2005 to 178 in 2010. In 2011, FDA tracked over 250 drug shortages. Drug shortages can create significant public health concerns. Causes of drug shortages may include: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">product quality concerns,</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">manufacturing problems,</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">difficulty in acquiring component parts or active pharmaceutical ingredients (API),</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">increases in demand, and</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">shipping delays, among other things. </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">On October 31, 2011, FDA sent a letter to manufacturers of prescription products reminding them of their mandatory reporting requirements under section 506C and encouraging them to voluntarily report to the Agency any disruptions in supply that could lead to a product shortage, even beyond those situations covered by mandatory reporting. On the same day, the President issued Executive Order 13588 directing FDA to use all available administrative tools to expand the Agency’s efforts to combat the problem of drug shortages. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">In addition to these steps, FDA released <a href="http://www.policymed.com/2012/03/fda-guidance-notification-of-prescription-drug-or-biologic-product-drug-shortages.html">draft Guidance</a> to Industry on “<a href="http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM292426.pdf?source=govdelivery">Notification to FDA of Issues that May Result in a Prescription Drug or Biological Product Shortage</a>.” The Guidance to industry explains requirements for notification to FDA of a discontinuance of certain drug products under section 506C of the <a class="zem_slink" title="Federal Food, Drug, and Cosmetic Act" href="http://en.wikipedia.org/wiki/Federal_Food%2C_Drug%2C_and_Cosmetic_Act" target="_blank" rel="noopener wikipedia">Federal Food, Drug, and Cosmetic Act</a> (FD&C Act), as implemented by 21 C.F.R. §§ 314.81(b)(3)(iii) and 314.91. The guidance reflects amendments to the implementing regulations published as an interim final rule on December 19, 2011 (effective January 18, 2012). The guidance is only for drugs, regulated by <a class="zem_slink" title="Center for Drug Evaluation and Research" href="http://en.wikipedia.org/wiki/Center_for_Drug_Evaluation_and_Research" target="_blank" rel="noopener wikipedia">CDER</a>, and biologics, the <a class="zem_slink" title="Center for Biologics Evaluation and Research" href="http://en.wikipedia.org/wiki/Center_for_Biologics_Evaluation_and_Research" target="_blank" rel="noopener wikipedia">Center for Biologics Evaluation and Research</a> (CBER). </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Since FDA and the Obama Administration has taken action, FDA has been able to prevent 128 drug shortages, and FDA is seeing fewer numbers of shortages occur – 42 new drugs in shortage reported in 2012, compared to 90 new shortages at this time last year, according to FDA Commissioner Margaret Hamburg, M.D., who recently gave the public a “<a href="http://blogs.fda.gov/fdavoice/index.php/2012/05/six-month-check-up-fdas-work-on-drug-shortages/">Six Month Check-Up on FDA’s Work on Drug Shortages</a>.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Most recently, however, the U.S. House of Representatives Committee on Oversight and Government Reform <a href="http://www.policymed.com/2012/06/house-committee-on-oversight-and-government-reform-report-fdas-contribution-to-the-drug-shortage-crisis.html">issued a report</a>, which documents a critical shortage of generic injectable medications that has occurred following enforcement activity by the Food and Drug Administration (FDA) at companies and facilities where the drugs are made. In addition to this report, there has been media coverage showing that another cause for drug shortages is the <a href="http://www.policymed.com/2012/03/increasing-generic-drug-shortages-linked-to-government-price-controls.html">government’s price controls.</a></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>FDASIA – Title X</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Title X of FDASIA substantially amends the existing Federal Food, Drug & Cosmetic Act (FFDCA) drug shortage provisions. FDASIA eliminates the requirement that a manufacturer be the sole manufacturer of a drug to be subject to the drug shortage notice requirements. Additionally, FDASIA explicitly makes drugs used in emergency medical care or during surgery subject to drug shortage notice requirements. Previously, only drugs that were life-supporting, life-sustaining, or intended for use in the prevention of a debilitating disease or condition were subject to these requirements. New exclusions from the notice requirements include radiopharmaceutical drug products or any other product as designated by FDA. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Manufacturers covered by the FDASIA notice requirements must notify FDA of either “a permanent discontinuance in the manufacture of the drug or an interruption of the manufacture of the drug that is likely to lead to a meaningful disruption in the supply of that drug in the United States, and the reasons for such discontinuance or interruption.” Prior to these amendments, the exclusion only applied to products originally derived from human tissue and replaced by a recombinant product. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Previously, the FFDCA only required notification for discontinuance in the manufacture of a drug. Under FDASIA, manufacturers must notify FDA at least six months before the date of the discontinuance or interruption, or as soon as practicable if the six-month minimum is not possible. Previously, the FFDCA only specified that manufacturers must notify FDA at least six months prior to the date of discontinuance. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">To the maximum extent practicable, FDA must inform appropriate organizations — including physician, health provider, and patient organizations — of drug shortages. Within 30 days of receiving notice of a drug shortage pertaining to a controlled substance subject to a production quota, FDA will notify the Attorney General and request that the Attorney General increase the production quotas if FDA deems it necessary to address the shortage. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">If a manufacturer fails to submit information about a drug shortage as required, FDA must issue a letter informing it of the failure. Within 30 days of the issuance of the letter, the manufacturer must submit to FDA a written response setting forth the basis for noncompliance and providing the required drug shortage information. Within 45 days of the issuance of the letter, FDA must publish the letter and any response on the FDA’s website, unless FDA issued the letter in error or the manufacturer’s response shows that there was a reasonable basis for not notifying as required. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">FDASIA authorizes FDA to respond to a drug shortage by expediting the review of an ANDA or a supplement to an ANDA or NDA that could help mitigate or prevent the shortage. FDA may also expedite an inspection or re-inspection of an establishment that could help mitigate or prevent the shortage. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Within 18 months of the enactment of FDASIA, FDA must adopt a final regulation implementing these drug shortage requirements. FDA may also apply these requirements by regulation to biological products if FDA “determines such inclusion would benefit the public health.”<strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Annual Reporting on Drug Shortages (FDASIA § 1002)</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">By the end of calendar year 2013, and no later than the end of each calendar year thereafter, FDA must submit a report to Congress on drug shortage statistics, communication within FDA on addressing shortages, and actions taken by FDA to prevent or mitigate shortages.<strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Coordination; Task Force and Strategic Plan (FDASIA § 1003)</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">As soon as practicable after the enactment of FDASIA, FDA must establish a task force to develop and implement a strategic plan for enhancing FDA’s response to preventing and mitigating drug shortages. Among other issues, the plan must examine whether to establish a “qualified manufacturing partner program.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">A qualified manufacturer would need to have the capability and capacity to supply products determined or anticipated to be in shortage within a rapid timeframe. FDA must also consider whether incentives are necessary to encourage participation in a qualified manufacturing program. Within one year of the enactment of FDASIA, the task force must publish the strategic plan and submit it to Congress. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Prior to any enforcement action or issuance of a warning letter that could reasonably lead to a meaningful disruption in the supply of a drug as described above, FDA must ensure that there is communication with the appropriate FDA office with expertise in drug shortages. If after the communication, FDA determines that an enforcement action or warning letter “could reasonably cause or exacerbate a shortage of a drug,” then FDA must evaluate the risks associated with the shortage and the risks associated with the violation before taking action or issuing a letter, “unless there is imminent risk of serious adverse health consequences or death to humans.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The task force, strategic plan, communication, and risk evaluation requirements of section 1003 described above expire five years after the enactment of FDASIA. To allow healthcare providers and other third-party organizations an opportunity to report evidence of drug shortages, FDA must identify or establish a reporting mechanism.<strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Drug Shortage List (FDASIA § 1004)</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">FDA must maintain an up-to-date list of drugs determined by FDA to be in shortage in the United States. For each drug on the list, FDA must include the following: the name of the drug, the name of the manufacturer, the reason for the shortage, and the estimated duration of the shortage as determined by FDA. The information in the list must be publicly available, unless the information involves trade secrets or confidential information, or if FDA “determines that disclosure of such information would adversely affect the public health (such as by increasing the possibility of hoarding or other disruption of the availability of drug products to patients).”<strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Quotas Applicable to Drugs in Shortage (FDASIA § 1005)</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Section 1005 amends the Controlled Substances Act to allow manufacturers of a schedule II controlled substance that is on FDA’s list of drugs in shortage to request an increase in production quotas from the Attorney General. Within 30 days of such a request, the Attorney General must review the request and decide whether increasing production quotas is necessary to address a shortage of a controlled substance. If the Attorney General determines that the level requested is not necessary to address a shortage of a controlled substance, the Attorney General must provide a written response detailing the basis for the determination and publish the response on FDA’s website.<strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Attorney General Report on Drug Shortages (FDASIA § 1006)</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Within six months of the enactment of FDASIA, the Attorney General must submit to Congress a report on drug shortages that: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">identifies the number of requests received under section 1005, the average review time for such requests, the number of requests granted and denied, and, for each of the requests denied, the basis for such denial;</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">describes the coordination between the Drug Enforcement Administration and FDA on efforts to prevent or alleviate drug shortages; and</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">identifies drugs containing a controlled substance subject to section 1005 when FDA determines such a drug is in shortage.<strong> </strong></span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Hospital Repackaging of Drugs in Shortage (FDASIA § 1007)</strong><strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">A hospital may repackage a drug (excluding controlled substances) for transfer to another hospital within the same health system and need not register as a repackager if: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">the drug is listed on FDA’s drug shortage list, or it is during the 60-day period following a period when the drug was on the list;</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">the drug is not sold or otherwise distributed by the health system or a hospital within the system to an entity or individual that is not a hospital within such health system; and</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">repackaging completed in compliance with applicable State requirements. </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">This exception does not apply starting on the date on which FDA “issues final guidance that clarifies the policy of the Food and Drug Administration regarding hospital pharmacies repackaging and safely transferring repackaged drugs to other hospitals within the same health system during a drug shortage.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Study on Drug Shortages (FDASIA § 1008)</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Within 18 months of the enactment of FDASIA, GAO must submit a report to Congress on the cause of drug shortages and on recommendations on how to prevent or alleviate shortages.</span></p> <div class="zemanta-pixie" style="margin-top: 10px; height: 15px;"><a class="zemanta-pixie-a" title="Enhanced by Zemanta" href="http://www.zemanta.com/?px"><img decoding="async" class="zemanta-pixie-img" style="float: right;" src="http://img.zemanta.com/zemified_e.png?x-id=f3a1da64-bec8-4cbc-95d6-2e7706ee150c" alt="Enhanced by Zemanta" /></a></div> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2012/07/fda-recently-signed-pdufa-5-provisions-to-address-drug-shortages.html/feed</wfw:commentRss> <slash:comments>1</slash:comments> </item> <item> <title>FDA: Food and Drug Administration Safety and Innovation Act (FDASIA) and Patient Focused Drug Development</title> <link>https://www.policymed.com/2012/07/fda-food-and-drug-administration-safety-and-innovation-act-fdasia-and-patient-focused-drug-developme.html</link> <comments>https://www.policymed.com/2012/07/fda-food-and-drug-administration-safety-and-innovation-act-fdasia-and-patient-focused-drug-developme.html#respond</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Tue, 17 Jul 2012 00:26:00 +0000</pubDate> <category><![CDATA[FDA]]></category> <category><![CDATA[Innovation]]></category> <category><![CDATA[PDUFA]]></category> <category><![CDATA[Barack Obama]]></category> <category><![CDATA[Drug development]]></category> <category><![CDATA[FDASIA]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[Mullin]]></category> <category><![CDATA[NEW]]></category> <category><![CDATA[Prescription Drug User Fee Act]]></category> <category><![CDATA[Risk management]]></category> <guid isPermaLink="false">http://www.policymed.com/fda-food-and-drug-administration-safety-and-innovation-act-fdasia-and-patient-focused-drug-developme/</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="400" height="300" src="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167688ceca1970b-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167688ceca1970b-800wi.jpg 400w, https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167688ceca1970b-800wi-300x225.jpg 300w, https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167688ceca1970b-800wi-86x64.jpg 86w" sizes="auto, (max-width: 400px) 100vw, 400px" /></div>Last week, President Obama signed into law the Food and Drug Administration Safety and Innovation Act (FDASIA). Among the numerous provisions contained in this Act are several provisions that will enhance and increase patient participation in medical product regulation. Specifically, Sec. 1137 of the new law will allow the agency to develop and implement strategies to […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="400" height="300" src="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167688ceca1970b-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167688ceca1970b-800wi.jpg 400w, https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167688ceca1970b-800wi-300x225.jpg 300w, https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167688ceca1970b-800wi-86x64.jpg 86w" sizes="auto, (max-width: 400px) 100vw, 400px" /></div><p><span style="font-family: arial,helvetica,sans-serif;">Last week, <a class="zem_slink" title="Barack Hussein Obama, Jr." href="http://www.biography.com/people/barack-obama-12782369" target="_blank" rel="biographycom noopener">President Obama</a> signed into law the <a class="zem_slink" title="Food and Drug Administration" href="http://maps.google.com/maps?ll=39.0353363,-76.9830894&spn=0.01,0.01&q=39.0353363,-76.9830894 (Food%20and%20Drug%20Administration)&t=h" target="_blank" rel="geolocation noopener">Food and Drug Administration</a> Safety and Innovation Act (FDASIA). Among the numerous provisions contained in this Act are several provisions that will enhance and increase <a class="zem_slink" title="Patient participation" href="http://en.wikipedia.org/wiki/Patient_participation" target="_blank" rel="noopener wikipedia">patient participation</a> in <a class="zem_slink" title="Medicine" href="http://en.wikipedia.org/wiki/Medicine" target="_blank" rel="noopener wikipedia">medical product</a> regulation. Specifically, Sec. 1137 of the new law will allow the agency to develop and implement strategies to solicit the views of patients during the medical product development process and consider the perspectives of patients during regulatory discussions. This will include: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Fostering participation of FDA Patient Representatives as Special Government Employees in appropriate agency meetings with medical product sponsors and investigators; and,</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Exploring means to provide for identification of FDA Patient Representatives who do not have any, or have minimal, financial interest in the medical products industry. </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">Consequently, Theresa Mullin, Ph.D. Associate Director for Planning and Informatics FDA <a class="zem_slink" title="Center for Drug Evaluation and Research" href="http://en.wikipedia.org/wiki/Center_for_Drug_Evaluation_and_Research" target="_blank" rel="noopener wikipedia">Center for Drug Evaluation and Research</a> (CDER) recently gave a <a href="http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM310754.pdf?source=govdelivery">presentation</a> on “Patient-Focused <a class="zem_slink" title="Drug development" href="http://en.wikipedia.org/wiki/Drug_development" target="_blank" rel="noopener wikipedia">Drug Development</a>.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Presentation</strong><strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Mullin first outlined FDA’s benefit-risk (B-R) framework, which looks at five (5) key considerations: </span></p> <ol> <li><span style="font-family: arial,helvetica,sans-serif;">Severity of Condition</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Unmet Medical Need</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Benefit</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Risk</span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><a class="zem_slink" title="Risk management" href="http://en.wikipedia.org/wiki/Risk_management" target="_blank" rel="noopener wikipedia">Risk Management</a><strong> </strong></span></li> </ol> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Severity of Condition </strong>and <strong>Unmet Medical Need </strong>provide regulators with the clinical context for weighing benefits and risks and the associated uncertainties. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Benefit </strong>and <strong>Risk </strong>incorporate expert judgments based on evaluation of the efficacy and safety data. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Risk Management </strong>incorporates expert judgments on the expected impact of efforts to reduce and further characterize risks. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Assessment of a drug’s benefits and risks involves analysis of severity of condition and current state of the treatment armamentarium. Patients who live with a disease have a direct stake in drug review process and are in a unique position to contribute to drug development. As a result, FDA noted that its review process could benefit from systematic approach to obtaining patient perspective on disease severity or unmet medical need. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Mullins noted how FDASIA – the provisions reauthorizing the <a class="zem_slink" title="Prescription Drug User Fee Act" href="http://en.wikipedia.org/wiki/Prescription_Drug_User_Fee_Act" target="_blank" rel="noopener wikipedia">Prescription Drug User Fee Act</a> (PDUFA) – provides resources to support additional program staff to expand activities dedicated to providing review divisions with patient input. FDA will convene meetings with participation from review divisions, the relevant patient advocacy community, and other interested parties. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">FDA will hold four public workshops per year—a total of 20 meetings over 5 years. Each meeting will focus on a different disease area, reviewing the armamentarium for that indication, and identifying areas of unmet need.<strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Benefit</strong><strong>‐</strong><strong><a class="zem_slink" title="Risk assessment" href="http://en.wikipedia.org/wiki/Risk_assessment" target="_blank" rel="noopener wikipedia">Risk Assessment</a> Framework: Analysis of Condition</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Assessing Evidence and Uncertainties– for a given drug for a given indication‐questions FDA considers include: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What is the treated (or prevented) condition?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What are its clinical manifestations (i.e., symptoms that are either reported or observed)?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What is known about the natural history and progression of the condition, including in specific subpopulations?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>How severe is the condition for those who have it?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>How does severity vary across the sub</em><em>‐</em><em>populations we have defined? (Note specific subpopulations and nature of differences.)</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What is the basis for our assessment of the condition and its severity? (Note any relevant literature, clinical experience, expert opinion, etc.)</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What are the major uncertainties in the available information? What are their implications?</em><strong> </strong></span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Benefit</strong><strong>‐</strong><strong>Risk Assessment Framework: Unmet Medical Need</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Assessing Evidence and Uncertainties –for a given drug for a given indication‐FDA considers: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What other pharmacological therapies are approved for this condition?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>How effective are these alternative therapies?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>How does their effectiveness vary by sub</em><em>‐</em><em>population?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>How well tolerated are these alternative therapies?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>How does tolerance vary by sub</em><em>‐</em><em>population?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What off</em><em>‐</em><em>label pharmacological therapies might be considered?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>How effective and how well tolerated are they reported or believed to be?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What non</em><em>‐</em><em>pharmacological therapies might be considered?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>How effective and how well tolerated are they reported or believed to be?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What kinds of evidence are available about the use of alternative treatments for this condition?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What is the strength of evidence in each case?</em></span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><em>What are the major uncertainties in the evidence? What are their implications?</em> </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">The presentation then discussed Patient‐Reported Outcome (PRO) Measures, which FDA defined as <strong>“</strong>any report of the status of a patient’s health condition coming directly from the patient, without interpretation by physicians or anyone, about how the patient functions or feels in relation to a health condition and its treatment.” FDA reviews PRO instruments and looks at whether the instrument measures the concept it is supposed to measure. FDA looks at whether the instrument is: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Well‐specified and reliable</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Specific for target population</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Specific for target indication</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Adequate measurement properties (e.g., content validity) </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">The presentation then noted that qualitative research can be used to establish PRO content validity. This might include: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Focus groups to generate a pool of patient outcome‐related domains and their components (e.g., What symptoms and functions or activities impacted by disease that are most important to patients)</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Surveys including a larger and more diverse sample patients with a given condition (e.g., examine the importance and relevance of domains identified by literature review, expert opinion or among a smaller set of patients, to validate these items and perhaps explore other measurement characteristics) </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">Mullins then used the example of people with chronic pain. Focus groups conducted with patients who experience chronic pain identified 19 aspects of their lives (outcome domains) that are significantly impacted by the presence of their symptoms and for which improvements were important criteria that they use in evaluating the effectiveness of any treatment. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Next Steps Patient</strong><strong>‐</strong><strong>Focused Drug Development</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Throughout the rest of this summer, FDA will develop preliminary list of 20 disease areas for public comment to inform planning for the set of 20 PDUFA V meetings. FDA will also develop a basic roadmap that could be used by patient groups interested in pursuing need for and development of PRO measures in a specific disease area. This roadmap will identify important but currently unaddressed aspects of their disease experience to potentially be considered in evaluating new therapies. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">In September 2012, FDA will publish an FR notice with the preliminary list of 20 disease areas for public comment. In October 2012, FDA will plan to hold public meeting to: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Discuss the proposed list of disease areas for the PDUFA meetings and get public input;</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Discuss strategies for getting broader public input and basic roadmap for identification of important patient outcomes and strategies for collaborative development PRO measures </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>FDA Patient Representative Program</strong><strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The Patient‐Focused Drug Development initiative will also add to the existing FDA programs designed to integrate patients’ perspectives. FDA’s patient advocacy programs are run by FDA’s Office of Special Health Issues. One of their main programs is the <a href="http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/patie%20ntinvolvement/ucm123858.htm">FDA Patient Representative Program</a>. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Patient Representatives provide FDA with the unique perspective of patients and family members directly affected by serious or life‐threatening disease. Patient Representatives serve in the several ways, including: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">On Advisory Committees, where they offer the patient perspective, ask questions, and give comments to assist the committee in making recommendations.</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">As consultants for review divisions –the clinicians and scientists who review data submitted to determine whether the product’s benefits outweigh the potential risks</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">As presenters at FDA meetings and workshops on disease‐specific or regulatory and health policy issues </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">The Programs activities include:</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"> </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Recruitment of New Patient Representatives</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Selection of Patient Representatives for: </span> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Advisory Committees</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Consultation with Review Division</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Conducts Training For Patient Representatives </span> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Individual FDA 101 Training</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Monthly Webinars</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Annual Workshop for Newly Recruited Patient Representatives </span></li> </ul> </li> </ul> </li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">In choosing Patient Representatives, FDA looks for someone who brings a personal viewpoint to the process and communicates a collective patient perspective. A <span style="text-decoration: underline;">patient </span>perspective is created when a person goes through personal experience with the disease. A <span style="text-decoration: underline;">collective patient </span>perspective is created when the person has knowledge of others’ disease experiences and conveys this collective patient perspective.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"> Patient Representatives provide Advisory Committee and FDA insight on issues, problems, and/or questions pertinent to the viewpoint of patients and family members living with a specific serious or life‐threatening disease. </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Personal experience with/knowledgeable about the specific illness</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Ability to articulate the perspective of patients</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Experience as a patient advocate</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Formal affiliation with a patient advocacy organization</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">The ability to identify issues through communication with patient constituencies </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">Patient Representatives serve on an Advisory Committee when a product or therapy related to specific illness is under review, as either voting or non‐voting member </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Voting: must be appointed as special government employees (SGEs); requires disclosure of personal financial information to the FDA in order to determine whether their financial interests pose a possible conflict of interest on an advisory committee</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Non‐voting: may only vote on procedural matters concerning the conduct of the meeting</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">In both cases: expected to provide the patient perspective, ask questions, and offer comments to assist the committee in making recommendations<strong> </strong></span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Drug Development Patient Consultant Program</strong> </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">FDA also uses patients in its Drug Development Patient Consultant program. This program incorporates the perspective of patient advocates into the drug development process; allows opportunity to participate in the FDA drug review regulatory process. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Patients are selected to participate in meetings by matching a specific illness and proposed indication for the new therapeutic drug being developed. Patients may participate in meetings (via telephone ) between the FDA and drug companies. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The newly selected patient consultant receives training and participates in monthly telephone lecture series in preparation for these meetings. To provide consultation to both FDA and the drug company, it is important that the patient consultant have background information on the drug under review. About three weeks before each meeting, the patient consultant is mailed the meeting package containing the meeting issues and questions. The patient consultant reviews the meeting package in preparation for the meeting.</span></p> <div class="zemanta-pixie" style="margin-top: 10px; height: 15px;"><a class="zemanta-pixie-a" title="Enhanced by Zemanta" href="http://www.zemanta.com/?px"><img decoding="async" class="zemanta-pixie-img" style="float: right;" src="http://img.zemanta.com/zemified_e.png?x-id=d86e680d-2f41-446e-ad41-8e5f81e8e47e" alt="Enhanced by Zemanta" /></a></div> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2012/07/fda-food-and-drug-administration-safety-and-innovation-act-fdasia-and-patient-focused-drug-developme.html/feed</wfw:commentRss> <slash:comments>0</slash:comments> </item> <item> <title>FDA Releases Final Risk Evaluation and Mitigation Strategies (REMS) for Extended Release/Long Acting Opioids Including a Prescriber Education Program</title> <link>https://www.policymed.com/2012/07/fda-releases-final-risk-evaluation-and-mitigation-strategies-rems-for-extended-releaselong-acting-opioids-including-a-pres.html</link> <comments>https://www.policymed.com/2012/07/fda-releases-final-risk-evaluation-and-mitigation-strategies-rems-for-extended-releaselong-acting-opioids-including-a-pres.html#respond</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Mon, 09 Jul 2012 17:47:04 +0000</pubDate> <category><![CDATA[CME]]></category> <category><![CDATA[FDA]]></category> <category><![CDATA[REMS]]></category> <category><![CDATA[Centers for Disease Control and Prevention]]></category> <category><![CDATA[Continuing education]]></category> <category><![CDATA[Education]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[NEW]]></category> <category><![CDATA[Opioid]]></category> <category><![CDATA[Substance abuse]]></category> <guid isPermaLink="false">http://www.policymed.com/fda-releases-final-risk-evaluation-and-mitigation-strategies-rems-for-extended-releaselong-acting-opioids-including-a-pres/</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="320" height="187" src="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167685643e2970b-320wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167685643e2970b-320wi.jpg 320w, https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167685643e2970b-320wi-300x175.jpg 300w" sizes="auto, (max-width: 320px) 100vw, 320px" /></div>After three years of work the Food and Drug Administration (FDA) released its final Risk Evaluation and Mitigation Strategies (REMS) for extend-release (ER) and long-acting (LA) opioid medications. This is the first time that the FDA has mandated a class wide REMS and much of what is recommended will be looked at closely for future […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="320" height="187" src="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167685643e2970b-320wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167685643e2970b-320wi.jpg 320w, https://www.policymed.com/wp-content/uploads/2012/07/6a00e5520572bb88340167685643e2970b-320wi-300x175.jpg 300w" sizes="auto, (max-width: 320px) 100vw, 320px" /></div><p><span style="font-family: arial,helvetica,sans-serif;">After three years of work the <a class="zem_slink" title="Food and Drug Administration" href="http://maps.google.com/maps?ll=39.0353363,-76.9830894&spn=0.01,0.01&q=39.0353363,-76.9830894 (Food%20and%20Drug%20Administration)&t=h" target="_blank" rel="geolocation noopener">Food and Drug Administration (FDA)</a> released its <a href="http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163647.htm">final Risk Evaluation and Mitigation Strategies (REMS</a>) for extend-release (<a class="zem_slink" title="ER" href="http://www.nbc.com/ER/" target="_blank" rel="hulu noopener">ER</a>) and long-acting (LA) opioid medications. This is the first time that the FDA has mandated a class wide REMS and much of what is recommended will be looked at closely for future class REMS. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">ER/LA opioids are highly potent drugs that are approved to treat moderate to severe persistent pain for serious and chronic conditions (<a href="http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm251735.htm">list of ER/LA opioid products</a>). The misuse and abuse of these drugs have resulted in a serious public health crisis of addiction, overdose, and death. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">After input from many stakeholders dating back to <a href="http://www.policymed.com/2011/11/fda-rems-blue-print-for-prescriber-continuing-education-program-for-extended-release-long-acting-opioids.html">November 2011</a>, the Food and Drug Administration (FDA) also released the “<a href="http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM277916.pdf">Blueprint for Prescriber Continuing Education Program</a>” regarding the use of opioids. The Blueprint contains core messages intended for use by continuing education (<a class="zem_slink" title="Common Era" href="http://en.wikipedia.org/wiki/Common_Era" target="_blank" rel="noopener wikipedia">CE</a>) providers to develop educational materials to train prescribers of long-acting and extended release opioids under the required risk evaluation and mitigation strategy (REMS) for these products (Opioid REMS). </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">A REMS is a risk management plan that goes beyond requirements in the drug prescribing information to manage serious risks associated with a drug. The <a class="zem_slink" title="Food and Drug Administration Amendments Act of 2007" href="http://en.wikipedia.org/wiki/Food_and_Drug_Administration_Amendments_Act_of_2007" target="_blank" rel="noopener wikipedia">Food and Drug Administration Amendments Act of 2007</a> gave FDA the authority to require companies to develop and implement a REMS when necessary to ensure that the benefits of a drug or biological product outweigh its risks. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The <a href="http://cmecoalition.org/">CME Coalition</a> offered its <a href="http://www.prlog.org/11919680-cme-coalition-applauds-fda-approval-of-rems-for-erla-opioid-analgesics.html">strong support</a> for FDA’s efforts. Andrew Rosenberg, Senior Advisor to the CME Coalition stated, “When there is a public health imperative, such as the abuse of long acting opioids, continuing education of providers is integral to improving patient outcomes and advancing the health of the country.” Rosenberg continued, “We are pleased that the FDA views CME as a change agent and valuable resource to improve caregiver behavior in this vital area.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">FDA’s final REMS is important because it marks a crucial step in federal health care agencies for recognizing the importance of CE and continuing medical education (CME). The Agency’s logical and reasoned approach towards working with industry and accredited CE providers is a significant step in the right direction not only for patients and physicians but for the future of our healthcare system. The opioid REMS represents the cross-collaboration of CE providers, industry, consumers, patients, and FDA. Moving forward, FDA and these stakeholders should look at other opportunities to collaborate and use CE/CME to improve patient outcomes, reduce healthcare costs, and lower safety risks. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Background</strong><strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><a class="zem_slink" title="Opioid" href="http://en.wikipedia.org/wiki/Opioid" target="_blank" rel="noopener wikipedia">Opioids</a> are widely prescribed and carry a risk of abuse, misuse and death. In 2009, there were nearly 425,000 emergency department visits involving non-medical use of opioid analgesics. According to estimates from the <a class="zem_slink" title="Centers for Disease Control and Prevention" href="http://maps.google.com/maps?ll=33.798817,-84.325598&spn=0.01,0.01&q=33.798817,-84.325598 (Centers%20for%20Disease%20Control%20and%20Prevention)&t=h" target="_blank" rel="geolocation noopener">Centers for Disease Control and Prevention</a>, 14,800 Americans died from overdoses involving opioid <a class="zem_slink" title="Analgesic" href="http://en.wikipedia.org/wiki/Analgesic" target="_blank" rel="noopener wikipedia">pain relievers</a> in 2008. In 2009, there were 15,597 deaths involving an opioid medication. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The REMS is part of a federal initiative to address the <a class="zem_slink" title="Substance abuse" href="http://en.wikipedia.org/wiki/Substance_abuse" target="_blank" rel="noopener wikipedia">prescription drug abuse</a>, misuse, and overdose epidemic. The REMS introduces new safety measures designed to reduce risks and improve the safe use of ER/LA opioids, while ensuring access to needed medications for patients in pain. FDA is requiring a REMS for ER/LA opioid analgesics because FDA has concluded that there is a disproportionate safety problem associated with these products that must be addressed. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">“Misprescribing, misuse, and abuse of extended-release and long-acting opioids are a critical and growing public health challenge,” said <a href="http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm310870.htm">FDA Commissioner Margaret A. Hamburg, M.D.</a> “The FDA’s goal with this REMS approval is to ensure that health care professionals are educated on how to safely prescribe opioids and that patients know how to safely use these drugs.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">All ER/LA opioid analgesics will be required to have a REMS. The new ER/LA opioid REMS will affect more than 20 companies that manufacture these opioid analgesics. Under the new REMS, companies will be required to make <a class="zem_slink" title="Education" href="http://en.wikipedia.org/wiki/Education" target="_blank" rel="noopener wikipedia">education programs</a> available to prescribers based on an FDA Blueprint. It is expected that companies will meet this obligation by providing educational grants to accredited continuing education (CE) providers to offer training to prescribers at no or nominal cost. These CE activities must cover the content and messages of a <a href="http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM277916.pdf">blueprint</a> developed by FDA for this purpose. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The REMS also will require companies to make available FDA-approved patient education materials on the safe use of these drugs. The companies will be required to perform periodic assessments of the implementation of the REMS and the success of the program in meeting its goals. The FDA will review these assessments and may require additional elements to achieve the goals of the program. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">“We commend the FDA for taking action to save lives by increasing access to prescriber education,” said Gil Kerlikowske, director of the Office of National Drug Control Policy. “Since day one, the Obama Administration has been laser focused on addressing the prescription drug abuse epidemic and today’s action is an important contribution to this comprehensive effort.” The new ER/LA opioid analgesics REMS is also part of the <a href="http://www.whitehouse.gov/sites/default/files/ondcp/issues-content/prescription-drugs/rx_abuse_plan.pdf" target="_blank" rel="noopener">national prescription drug abuse plan </a>announced by the Obama Administration in 2011 to combat prescription drug misuse and abuse. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">ER/LA opioid analgesics are widely prescribed medicines with an estimated 22.9 million prescriptions dispensed in 2011, according to IMS Health, which provides services and information to the health care and pharmaceutical industries. It is estimated that more than 320,000 prescribers registered with the Drug Enforcement Administration (DEA) wrote at least one prescription for these drugs in 2011. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">ER/LA opioid analgesics are associated with serious risks of overuse, abuse, misuse and death and the numbers continue to rise. According to the Centers for Disease Control and Prevention, 14,800 Americans died from overdoses involving opioids in 2008. In 2009, there were 15,597 deaths involving these medications – nearly four times as many deaths compared to 1999. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">“There are a limited number of options available for the treatment of pain. Opioids are one option, but they carry a significant risk of misuse, abuse, overdose and death,” says Sharon Hertz, M.D., deputy director of FDA’s Division of Anesthesia, Analgesia and Addiction Products. “We’re trying to help physicians manage the risks and improve the safety of using these medicines.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">“Misuse and abuse of prescription opioids is a complex problem and demands a holistic response,” said John Jenkins, M.D., director of CDER’s Office of New Drugs. “The new REMS program is one component of a multi-agency, national strategy to address this important public health issue.”<strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Role of CME</strong><strong> </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The central component of the ER/LA opioid analgesics REMS is an education program for prescribers (e.g., physicians, nurse practitioners, physician assistants).<strong> </strong>There are approximately 320,000 prescribers of ER/LA opioid analgesics in the United States, and FDA expects companies to train 25% of these prescribers at the end of the first year following implementation of the program, 50% after two years, and 60% of them within three years of the start of training. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">It is expected that the first continuing education activities under the REMS will be offered to prescribers by March 1, 2013. The FDA expects the training to take approximately 3 hours, but the CE providers will determine the number of CE credit hours that will be offered for the courses based on established standards for such determinations. Key components of the ER/LA opioid analgesics REMS include: </span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;"><strong>Training for prescribers.</strong> Based on an FDA Blueprint, developed with input from stakeholders, educational programs for prescribers of ER/LA opioids will include information on weighing the risks and benefits of opioid therapy, choosing patients appropriately, managing and monitoring patients, and counseling patients on the safe use of these drugs. In addition, the education will include information on how to recognize evidence of, and the potential for, opioid misuse, abuse, and addiction, and general and specific drug information for ER/LA opioid analgesics. </span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><strong>Updated Medication Guide and patient counseling document.</strong> These materials contain consumer-friendly information on the safe use, storage and disposal of ER/ LA opioid analgesics. Included are instructions to consult one’s physician or other prescribing health care professional before changing doses; signs of potential overdose and emergency contact instructions; and specific advice on safe storage to prevent accidental exposure to family members and household visitors. </span></li> <li><span style="font-family: arial,helvetica,sans-serif;"><strong>Assessment/auditing.</strong> Companies will be expected to achieve certain FDA-established goals for the percentage of prescribers of ER/ LA opioids who complete the training, as well as assess prescribers’ understanding of important risk information over time. The assessments also cover whether the REMS is adversely affecting patient access to necessary pain medications, which manufacturers must report to FDA as part of periodic required assessments. </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">It is expected that the first continuing education activities under the REMS will be offered to prescribers by March 1, 2013. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Follow-up surveys will be conducted to assess prescriber understanding of the important safety information and assess whether the REMS is adversely affecting patient access to necessary pain medications. Companies plan to offer additional funding to CE providers as an incentive to identify and track prescribers who take the REMS-compliant training and to perform follow-up surveys to assess the amount of information retained. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">As part of the REMS, companies will report periodically on actions taken to implement the REMS, including, for training provided by CE providers, the number of grants awarded to CE providers, the number of prescribers trained, and other relevant information. If FDA determines that the REMS is not meeting its goals, the Agency will re-evaluate the program. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">There is no mandatory requirement that prescribers take the training and no precondition to prescribing ER/LA opioids to patients. However, the Obama Administration endorsed a mandatory training program on responsible opioid prescribing practices in April 2011 as part of its comprehensive plan to address the epidemic of prescription drug abuse. The program, which would be linked to DEA registration by providers, would require legislative changes that are being pursued by the Administration. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The FDA continues to support this approach, but absent the needed legislation, intends to exercise its authority to require mandatory elements for companies and voluntary elements for prescribers – all of which are important and necessary steps to help curb the misuse and abuse of ER/ LA opioid analgesics, without being overly burdensome. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">For patients, the benefit is two-fold. First, Hertz notes that health care professionals who participate in the REMS program will have more knowledge and awareness and can have frank conversations with their patients about the risks and appropriate use of opioids. A new patient counseling document will be available for prescribers to use when talking to their patients about these medications. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The REMS also includes an updated Medication Guide—a paper handout for patients that the pharmacist will provide when a patient receives an ER/LA opioid medication. This document, Hertz says, is written in plain language to simply explain how to safely use ER/LA opioid medicines. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The American Academy of Pain Medicine, which represents 2,600 pain physicians and treatment teams, issued <a href="http://www.marketwatch.com/story/american-academy-of-pain-medicine-applauds-fda-action-to-enhance-patient-safety-on-prescribing-opioids-offers-aapm-safe-opioid-prescribing-course-as-educational-model-2012-07-09">a statement</a> supporting FDA’s issuance of the REMS for opioids, calling it a “huge leap forward.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;"> “Through proper education and training, opioids can be administered safely to patients and continue to be an important option in the treatment of chronic and debilitating pain that is suffered by millions of Americans.” AAPM will also shortly be issuing a series of best practices for both patients and prescribers that can further reduce adverse outcomes associated with opioids. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Purdue Pharma L.P., maker of several opioids including OxyContin®, also <a href="http://www.marketwatch.com/story/purdue-pharma-lp-comments-on-fda-announcement-on-rems-for-extended-release-and-long-acting-opioid-analgesics-2012-07-09">announced</a> its support for FDA’s REMS for opioids. </span></p> <div class="zemanta-pixie" style="margin-top: 10px; height: 15px;"><a class="zemanta-pixie-a" title="Enhanced by Zemanta" href="http://www.zemanta.com/?px"><img decoding="async" class="zemanta-pixie-img" style="float: right;" src="http://img.zemanta.com/zemified_e.png?x-id=2d228d14-7db6-4e7f-b461-8420fe95120e" alt="Enhanced by Zemanta" /></a></div> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2012/07/fda-releases-final-risk-evaluation-and-mitigation-strategies-rems-for-extended-releaselong-acting-opioids-including-a-pres.html/feed</wfw:commentRss> <slash:comments>0</slash:comments> </item> <item> <title>The Cultivating Scientific Expertise to Foster Innovation for Patients Act of 2011: House Introduces Bill to Relieve FDA of Burdensome Conflict of Interest Quotas</title> <link>https://www.policymed.com/2011/10/the-cultivating-scientific-expertise-to-foster-innovation-for-patients-act-of-2011-house-introduces-bill-to-relieve-fda-of-b.html</link> <comments>https://www.policymed.com/2011/10/the-cultivating-scientific-expertise-to-foster-innovation-for-patients-act-of-2011-house-introduces-bill-to-relieve-fda-of-b.html#respond</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Thu, 20 Oct 2011 00:01:00 +0000</pubDate> <category><![CDATA[Congress]]></category> <category><![CDATA[FDA]]></category> <category><![CDATA[(R-TX)]]></category> <category><![CDATA[Congressman Michael Burgess]]></category> <category><![CDATA[FDA Renewing Efficiency from Outside Review Management Act of 2011]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[M.D.]]></category> <category><![CDATA[NEW]]></category> <category><![CDATA[The Cultivating Scientific Expertise to Foster Innovation for Patients Act of 2011]]></category> <guid isPermaLink="false">http://www.policymed.com/the-cultivating-scientific-expertise-to-foster-innovation-for-patients-act-of-2011-house-introduces-bill-to-relieve-fda-of-b/</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="320" height="217" src="https://www.policymed.com/wp-content/uploads/2011/10/6a00e5520572bb883401539271b6ef970b-320wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2011/10/6a00e5520572bb883401539271b6ef970b-320wi.jpg 320w, https://www.policymed.com/wp-content/uploads/2011/10/6a00e5520572bb883401539271b6ef970b-320wi-300x203.jpg 300w" sizes="auto, (max-width: 320px) 100vw, 320px" /></div>As we noted last week, a group of bipartisan Senators including Senators Amy Klobuchar (D-MN), Richard Burr (R-NC), and Michael Bennet (D-CO) introduced The “Medical Device Regulatory Improvement Act (S. 1700) “to help boost medical innovation by reducing regulatory burdens that unnecessarily delay beneficial new medical products from reaching patients.” The legislation would help streamline […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="320" height="217" src="https://www.policymed.com/wp-content/uploads/2011/10/6a00e5520572bb883401539271b6ef970b-320wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2011/10/6a00e5520572bb883401539271b6ef970b-320wi.jpg 320w, https://www.policymed.com/wp-content/uploads/2011/10/6a00e5520572bb883401539271b6ef970b-320wi-300x203.jpg 300w" sizes="auto, (max-width: 320px) 100vw, 320px" /></div><p><span style="font-family: arial,helvetica,sans-serif;">As we noted last week, a group of bipartisan Senators including <a href="http://klobuchar.senate.gov/newsreleases_detail.cfm?id=334474&">Senators Amy Klobuchar</a> (D-MN), Richard Burr (R-NC), and Michael Bennet (D-CO) introduced The “<a href="http://policymed.typepad.com/files/the-medical-device-regulatory-improvement-act.pdf"><em>Medical Device Regulatory Improvement Act</em></a> (<a href="http://www.gpo.gov/fdsys/pkg/BILLS-112s1700is/pdf/BILLS-112s1700is.pdf">S. 1700</a>) “to help boost medical innovation by reducing regulatory burdens that unnecessarily delay beneficial new medical products from reaching patients.” The legislation would help streamline the Food and Drug Administration’s (FDA) regulation of medical devices to continue to spur innovation and help get new, lifesaving products to the market quicker without compromising consumer safety. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">More importantly, the legislation would restore the appropriate balance to conflicts of interest requirements by requiring the FDA to be subject to the same conflicts of interest requirements as the rest of the federal government, under the Federal Advisory Committee Act. The legislation would also direct the FDA to contract with an outside entity to conduct a thorough review of the management and regulatory processes at the FDA’s Center for Devices and Radiological Health, including the impact on medical device innovation.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><em>A companion bill in the House was also introduced by Representative Erik Paulsen (R-MN) and an equally impressive group of bipartisan legislators. The </em><strong>FDA Renewing Efficiency from Outside Review Management Act of 2011 (</strong><a href="http://www.gpo.gov/fdsys/pkg/BILLS-112hr3205ih/pdf/BILLS-112hr3205ih.pdf">H.R. 3205</a><strong>) </strong>reauthorizes the third party inspection program and reforms the third party review program to foster better participation, decrease approval times and conserve FDA resources.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Additionally, last week, Congressman Michael Burgess, M.D., (R-TX) introduced <strong>The Cultivating Scientific Expertise to Foster Innovation for Patients Act of 2011</strong> (<a href="http://www.gpo.gov/fdsys/pkg/BILLS-112hr3206ih/pdf/BILLS-112hr3206ih.pdf">H.R. 3206</a>) to help FDA obtain expert advice on advisory committees by eliminating limits on the number of conflict of interest waivers FDA can issue. The bill would instruct the Department of Health and Human Services (HHS) Secretary, when considering potential conflicts of interest, to consider the totality of the type, nature and magnitude of any financial interest, without focusing on any one factor over another.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Although the Burgess bill does not directly touch upon CME, his office was represented at the <a href="http://www.policymed.com/2011/09/cme-coalition-congressional-briefing-on-breast-cancer-and-cme.html">CME Coalition briefing last month</a>. In announcing the legislation, Dr. Burgess noted that:</span></p> <p style="padding-left: 30px;"><span style="font-family: arial,helvetica,sans-serif;">We need to improve the FDA process for the products they do regulate and that is why we need to ensure the most qualified experts are available to the agency. In the important task of evaluating products that can improve the health of American patients, we want the best of the best. Setting arbitrary waiver limits not only clogs the already overwhelmed FDA process, but encourages membership by lesser qualified individuals. In the arena of life-altering medical treatments, this is unacceptable. Long delays due to vacancies and panels with lesser qualified members put lives unnecessarily at risk.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">It should be noted that the House bills above, are included in a package of ten (10) bills that the House Energy and Commerce Committee is considering. In a <a href="http://energycommerce.house.gov/news/PRArticle.aspx?NewsID=9020">press release,</a> the Committee called these bills “Ten Specific Solutions to Top Ten Challenges in Current Review Process that Slow Access to Vital Devices.” Other pieces of legislation include proposals that would change premarket predictability, the 510(k) process, and humanitarian device reforms. It is likely that members of both the Senate and House will try to get these pieces of legislation included in the Prescription Drug User Fee Act (PDUFA) V negotiations. A draft bill will most likely come sometime next summer. </span></p> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2011/10/the-cultivating-scientific-expertise-to-foster-innovation-for-patients-act-of-2011-house-introduces-bill-to-relieve-fda-of-b.html/feed</wfw:commentRss> <slash:comments>0</slash:comments> </item> <item> <title>Par Pharmaceuticals vs. FDA Calling for Truthful Speech vs. FDA Approved</title> <link>https://www.policymed.com/2011/10/phar-pharmaceuticals-vs-fda-calling-for-truthful-speech-vs-fda-approved.html</link> <comments>https://www.policymed.com/2011/10/phar-pharmaceuticals-vs-fda-calling-for-truthful-speech-vs-fda-approved.html#respond</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Tue, 18 Oct 2011 00:02:00 +0000</pubDate> <category><![CDATA[Medical Legal]]></category> <category><![CDATA[FDA]]></category> <category><![CDATA[FDA Regulated Speech]]></category> <category><![CDATA[FDCA]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[IMS vs. Sorell]]></category> <category><![CDATA[NEW]]></category> <category><![CDATA[Par Pharmaceuticals]]></category> <category><![CDATA[Truthful Speech]]></category> <category><![CDATA[US District Court]]></category> <guid isPermaLink="false">http://www.policymed.com/phar-pharmaceuticals-vs-fda-calling-for-truthful-speech-vs-fda-approved/</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="214" height="130" src="https://www.policymed.com/wp-content/uploads/2014/01/6a00e5520572bb883401a3fb89b3bb970b.png" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" /></div>Last June, the United States Supreme Court, in a landmark decision, invalidated a Vermont law, which tried to restrict commercial speech of certain healthcare companies and stakeholders. In the IMS v. Sorell case, writing for the Majority, Justice Anthony Kennedy reasoned that, “Speech in aid of pharmaceutical marketing…is a form of expression protected by the […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="214" height="130" src="https://www.policymed.com/wp-content/uploads/2014/01/6a00e5520572bb883401a3fb89b3bb970b.png" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" /></div><p><span style="font-family: arial,helvetica,sans-serif;">Last June, the United States Supreme Court, in a landmark decision, invalidated a Vermont law, which tried to restrict commercial speech of certain healthcare companies and stakeholders. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">In the <a href="http://www.policymed.com/2011/06/us-supreme-court-sorrell-vs-ims-inc-court-upholds-data-mining.html"><em>IMS v. Sorell</em></a> case, writing for the Majority, Justice Anthony Kennedy reasoned that, “Speech in aid of pharmaceutical marketing…is a form of expression protected by the Free Speech Clause of the First Amendment,” and as “a consequence, Vermont’s statute must be subjected to heightened judicial scrutiny.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">In light of that decision, many legal and health policy authorities have begun to debate the impact of the <em>IMS </em>case on other areas of healthcare marketing and commercial speech. Consequently, a <a href="http://freepdfhosting.com/e8d67cbc9c.pdf">recent case filed</a> in the U.S. District Court for the District of Columbia, is likely to resolve this debate.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Par Pharmaceutical, Inc. v. FDA</strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The case, filed by <a href="http://investors.parpharm.com/phoenix.zhtml?c=81806&p=irol-newsArticle&ID=1617464&highlight=">Par Pharmaceutical, Inc</a>. against the Food and Drug Administration (FDA), seeks declaratory judgment against the agency and asserts the First Amendment and the Federal Food, Drug and Cosmetic Act (FDCA) bar application of certain regulations that FDA purport to criminalize Par’s “truthful and non-misleading speech to healthcare professionals concerning the FDA-approved use of its FDA-approved prescription drug.” As a result, they ask that the court invalidate the applicable FDA regulations and certain definitions and declare that a “manufacturer cannot be deemed to intend an off-label use merely because the manufacturer sells a drug with knowledge that physicians will prescribe the drug for an off-label use. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">John Kamp, Executive Director of the Coalition for Healthcare Communication, who played a critical role in the <em>IMS </em>case, noted that, “Par’s challenge goes directly to the heart of FDA’s jurisdiction to censor truthful speech by drug sponsors. After the Supreme Court decision in IMS, someone was bound to bring it. Now, the whole industry will be watching.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The specific product in question is Megace ES, which is used for the treatment of anorexia (loss of appetite), cachexia (severe malnutrition), or unexplained, significant weight loss in patients diagnosed with AIDS (“wasting”). The brief filed by Par contains detailed information and cites scientific evidence about the use of Megace. One particular piece of information stood out.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Specifically, Par acknowledged that the off-label use of megestrol acetate to treat wasting in cancer and geriatric patients is so widely accepted that “Par could not conduct placebo-controlled clinical trials that are the standard prerequisites to obtain FDA approval for a new use of an approved drug … because physicians would <strong>not </strong>agree to administer a placebo to cancer patients suffering from wasting, because the course of treatment would be contrary to the best interest of the patients, in light of the accepted off-label use of megestrol acetate.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Par also noted that CMS subsidizes off-label use of Megace ES to treat wasting in non-AIDS cancer and geriatric patients and is “medically accepted” for off-label uses.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Legal Background</strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">As noted by the brief filed by Par, FDA regulations provide that a pharmaceutical manufacturer commits a crime if it speaks to healthcare professionals about an FDA-approved prescription drug for a medical use that the FDA has not approved. The government commonly refers to manufacturers’’ speech about <em>unapproved uses </em>of approved drugs as “off-label promotion.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">However, these regulations do not limit or interfere with the authority of healthcare professionals to prescribe or administer any FDA-approved drug to any patient to treat any condition or disease. As FDA explained in its Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical devices, “once a drug or medical device has been approved or cleared by DFA, generally, healthcare professionals may lawfully use or prescribe that product for uses or treatment regiments that are <strong>not </strong>included in the product’s approved labeling.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Par asserted that FDA’s regulations also “purport to criminalize a manufacturer’s truthful and non-misleading speech about the <em>FDA-approved uses </em>of a prescription drug to physicians who may use the drug for approved uses but are more likely to use the drug for unapproved uses.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Based on these provisions, Par asserts that the “ongoing threat of prosecution for alleged ‘off-label promotion’ based on Par’s truthful and non-misleading speech to healthcare professionals concerning <em>FDA-approved use </em>of Par’s FDA-approved prescription drug currently <strong>chills </strong>Par’s speech. The brief cites to numerous recent cases and settlements from the Department of Justice and Inspector General and various press releases, in which government officials reaffirm their prosecutorial passion for off-label promotion cases. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Accordingly, Par filed suit, “seeking declaratory and injunctive relief to ensure its ability to engage in this protected speech free form the risk of criminal liability.” Moreover, Par asserts that FDA’s regulations are “contrary to constitutional right” and “arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law,” as applied to Par’s truthful and non-misleading speech to healthcare professions.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Specifically, Par argues that FDA and the government are interpreting the regulations “to prohibit a manufacturer from speaking to healthcare professionals about the FDA-approved, <em>on-label </em>uses of a prescription drug in a setting where physicians may prescribe the drug for both approved and unapproved uses.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Moreover, Par points out that under FDA’s definition of “labeling,” it is unlawful for a manufacturer to provide any tangible materials (i.e. brochures, booklets, mailing pieces, etc.) to healthcare professionals containing manufacturer-supplied drug information if those materials prescribe, recommend, or suggest an unapproved use of an approved prescription drug.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Par explains how the FDCA provides that a drug’s “labeling” must bear “adequate directions for use” as long as the drug’s “label” repeats the doctor’s directions to a patient set forth in the prescription itself. However, Par points out that an FDA regulation “nullifies this exemption by providing that a prescription drug’s labeling must bear “adequate directions for use” unless the label bears “adequate <em>information </em>for its use.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">FDA’s regulations define “adequate information” for a prescription drug’s use to mean directions under which medical professionals “can use the drug safely and for the purposes <em>for which it is intended</em>.” Under the regulation, a drug’s “intended” uses are not limited to the uses set forth in its FDA-approved labeling, but rather encompass “all purposes for which [the drug] is advertised or represented.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">If a manufacturer advertises or represents an approved prescription drug for an off-label use, the FDA’s regulation purports to require the manufacturer to provide “adequate directions” or “adequate information” for that off-label use in the drug’s labeling. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">However as Par pointed out, under these provisions, “a manufacturer cannot include directions or information for any off-label use in a drug’s “labeling,” or else the drug would constitute a “new drug” that cannot lawfully be sold.” Thus, Par asserted that, “a prescription drug that is “advertised or represented” for an off-label use necessarily lacks “adequate directions” and “adequate information” for that off-label use.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Under FDA’s regulation, the drug is then automatically “misbranded” and liable for criminal violations. Based on this reasoning, Par asserted that FDA’s regulation thus criminalizes the manufacturer’s truthful speech regarding a lawful, off-label use of an approved prescription drug.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Par also analyzed FDA’s regulation which defines a drug’s “intended uses” based on a manufacturer’s “objective intent,” which can be established based on the manufacturer’s “expressions” in any forum, including in “labeling claims, advertising matter, or oral or written statements.” The manufacturer’s “objective intent” also can be established based on “circumstances that the article is, with the knowledge of such persons or their representatives, offered and used for a purpose for which it is neither labeled nor advertised.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Under “the intended use” regulations, Par asserted that a manufacturer’s “speech concerning exclusively the FDA-approved, <em>on-label </em>uses of a prescription drug may demonstrate the manufacturer’s “objective intent” that the drug should be used for <em>off-label </em>purposes. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">For example, Par explained that, “if a manufacturer speaks about the on-label uses of a drug in a setting where physicians exercising independent medical judgment prescribe the drug off-label, the government interprets the FDA’s “intended use” regulations to require the manufacturer to provide “adequate directions” or “adequate information” for the off-label use in the drug’s labeling.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">However, as Par recognized, “if the manufacturer made such a modification to a drug’s FDA-approved “labeling,” the drug would constitute a “new drug” that could not lawfully be sold under the FDCA.” Accordingly, Par maintained that “when a manufacturer speaks about an on-label use of its drug in a medical facility where physciains prescribe the drug off-lable, the manufacturer is caught in a Catch-22: changing the drug’s labeling to add directions for the off-label use violates the Act’s criminal “new drug” rule, but based on the government’s view of the FDA’s “intended use” regulations, <em>not </em>changing the labeling to add those directions violates the Act’s criminal “misbranding” rule. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">The manufacturer’s “truthful speech about on-label use of its drug thus violates at least one of these criminal provisions.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Discussion</strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">As noted in Par’s brief, “once a drug is approved for marketing, FDA does not generally regulate how, and for what uses, physicians prescribe that drug,” and healthcare professionals may lawfully prescribe or administer an FDA-approved drug for uses that the FDA has not approved and thus are not included in the drug’s labeling.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Par recognized that “many off-label uses of FDA-approved prescription drugs are widespread, medically accepted, and subsidized by the federal government under the Medicare and Medicaid programs. “ They further emphasized that in “some medical specialities, such as oncology, the majority of prescriptions are written for off-label uses of approved drugs.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Par also pointed to the fact that FDA itself has acknowledged that “in certain circumstances, off label uses of approved products are appropriate, rational, and accepted medical practice.” They even cited to a statement from FDA Good Reprint Practices which clearly recognized that, “off-lable uses or treatment regimens may be important and may even constitute a medically recognized standard of care.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Because of the “widespread, medically accepted, and government-subsidized off-label uses of numerous FDA-approved prescription drugs,” Par argued that it is “critical that healthcare professionals have access to accurate, comprehensive, and current information concerning off-label uses.” Citing then-FDA Associate Commissioner for Health Affiars Stuart J. Nightingale, Par noted that the “principle for the FDA is that the very latest information that can be of value to physicians, pharmacists, and patients must be made available as soon as possible.” </span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Conclusion</strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Given the Supreme Court’s recent decision in <em>IMS </em>and the explicit language they used to protect the commercial speech of healthcare stakeholders, Par may have a strong case. For example, the majority in <em>IMS </em>noted that, “the fear that people would make bad decisions if given truthful information” cannot justify content-based burdens on speech.” The Court added that, laws “may not burden protected expression in order to tilt public debate in a preferred direction,” and that ““fear that speech might persuade provides no lawful basis for quieting it.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">It should also be noted that a <a href="http://www.wlf.org/Upload/litigation/briefs/USvCaronia-WLFAmicus.pdf">similar case</a>, filed by the Washington Legal Foundation, is being considered in the Second Circuit already, which could lead to a quicker route to the Supreme Court if the cases were consolidated. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">While it will likely be years before this case reaches the Supreme Court, it still sends a strong message to FDA and the Obama Administration’s efforts at prosecuting off-label promotion, especially given last year, the DOJ, as part of a settlement, asked Allergan to drop a similar First Amendment claim.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">It should be noted that if this case were to be decided in favor of Par and the industry, there is a possibility that the government would <strong>not </strong>appeal the case because if it were to make its way up to the Supreme Court and be decided in favor of industry, FDA and the Obama administration would have an extremely difficult precedent to overcome.</span></p> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2011/10/phar-pharmaceuticals-vs-fda-calling-for-truthful-speech-vs-fda-approved.html/feed</wfw:commentRss> <slash:comments>0</slash:comments> </item> <item> <title>FDA Updates 510K Approval Process for Medical Devices</title> <link>https://www.policymed.com/2011/01/fda-updates-510k-approval-process-for-medical-devices.html</link> <comments>https://www.policymed.com/2011/01/fda-updates-510k-approval-process-for-medical-devices.html#respond</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Thu, 20 Jan 2011 01:12:00 +0000</pubDate> <category><![CDATA[FDA]]></category> <category><![CDATA[510K]]></category> <category><![CDATA[Approvals]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[Medical Devices]]></category> <category><![CDATA[NEW]]></category> <guid isPermaLink="false">http://www.policymed.com/fda-updates-510k-approval-process-for-medical-devices/</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="278" height="181" src="https://www.policymed.com/wp-content/uploads/2011/01/6a00e5520572bb88340147e1c2c42a970b-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2011/01/6a00e5520572bb88340147e1c2c42a970b-800wi.jpg 278w, https://www.policymed.com/wp-content/uploads/2011/01/6a00e5520572bb88340147e1c2c42a970b-800wi-210x136.jpg 210w" sizes="auto, (max-width: 278px) 100vw, 278px" /></div>This week, the Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) announced new actions for the 510(k) program, the most commonly-used pathway to market for medical devices. The FDA’s CDRH uses this program to clear some 3,000 new medical devices for patients each year. Prior to announcing the new actions, President […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="278" height="181" src="https://www.policymed.com/wp-content/uploads/2011/01/6a00e5520572bb88340147e1c2c42a970b-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2011/01/6a00e5520572bb88340147e1c2c42a970b-800wi.jpg 278w, https://www.policymed.com/wp-content/uploads/2011/01/6a00e5520572bb88340147e1c2c42a970b-800wi-210x136.jpg 210w" sizes="auto, (max-width: 278px) 100vw, 278px" /></div><p><span style="font-family: arial,helvetica,sans-serif;">This week, the Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) announced <a href="http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDRH/CDRHReports/UCM239449.pdf">new actions for the 510(k) program</a>, the most commonly-used pathway to market for medical devices. The FDA’s CDRH uses this program to clear some 3,000 new medical devices for patients each year.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Prior to announcing the new actions, <a href="http://online.wsj.com/article/SB10001424052748703396604576088272112103698.html?mod=dist_smartbrief">President Obama wrote an editorial</a> in the Wall Street Journal asserting that the changes would result in “getting innovative and life-saving products to market faster.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">CDRH Director Jeffrey Shuren, M.D., J.D. told the public in a <a href="http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDRH/CDRHReports/UCM239451.pdf">letter</a> that the new 510(k) actions will increase the predictability, reliability, and efficiency of FDA’s regulatory pathways to help provide better treatments and diagnostics to patients more quickly, stimulate investment in and development of promising new technologies to meet critical public health needs, and increase the global market position of U.S. medical devices.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Background</strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">In September 2009, the 510(k) Working Group and the Task Force on the Utilization of Science in Regulatory Decision Making were formed to address critical challenges facing the CDRH and external constituencies.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Industry had raised concerns that the 510(k) program had become less predictable, consistent and transparent thereby stifling innovation and sending companies and jobs overseas, and that CDRH reviewers had become less responsive and more risk averse. Dr. Shuren noted that “an unpredictable environment discourages investment and stifles innovation, which, in turn, can spur companies to go overseas.”</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Consumers, third-party payers, and some healthcare professional groups were concerned that, for some devices, the 510(k) program did not provide adequate assurances of safety and effectiveness nor did it provide sufficient information for healthcare providers and patients to make well-informed treatment or diagnostic decisions. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">CDRH employees expressed concerns that the current 510(k) program failed to adapt to the increasing complexity of devices, and that reviewers’ ability to make well-informed decisions was undermined by the poor quality of 510(k) submissions. In addition, an increasing workload was straining an already overburdened program. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">In August 2010, <a href="http://www.policymed.com/2010/08/fda-proposes-changes-to-medical-device-510k-program.html">FDA’s CDRH released for public comment</a> the preliminary reports from these committees.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>510(k) New Actions</strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">According to the FDA’s newly released actions, to facilitate innovation in medical devices, the FDA will:</span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Streamline the review process for innovative, lower-risk products, called the “de novo” process; </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Publish guidance for industry to clarify when clinical data should be submitted to increase predictability and transparency; </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Develop a network of external experts who can use their knowledge and experience to help the agency address important scientific issues regarding new medical device technologies; </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Establish a new Center Science Council of senior FDA experts within the agency’s medical device center to assure more timely and consistent science based decision making; and</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Improve training for CDRH staff and industry</span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">While no medical device is completely risk-free, the FDA is strengthening its capacity to assess medical devices and monitor their safety once they are on the market and being used. To bolster the safety of medical devices, the FDA will:</span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">Establish a public database of important device information, such as medical device labeling and summaries of the basis for the FDA’s decision to clear specific devices; and </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">Require a brief description of scientific information regarding the safety and effectiveness known to the manufacturer for select higher-risk devices on a case by-case basis through device-specific guidance. </span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;"> FDA also released an <a href="http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDRH/CDRHReports/UCM239450.pdf">implementation plan</a> that outlines 25 specific actions and the timelines for completion or reaching a major milestone in 2011 to make the 510(k) program a blueprint for smarter medical device oversight; one that drives innovation and brings important technologies to the public. </span></p> <p><span style="font-family: arial,helvetica,sans-serif;">For some of the 25 Action Items listed in the chart, there will be additional opportunities for the public to provide input, where appropriate. Recommendations that are regulatory actions –such as draft guidance’s and proposed regulations – will have their own individual comment periods to give interested stakeholders an opportunity to comment on the draft proposals before they are finalized.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">FDA will also have a Public Meeting from April 7 – 8, 2011, on the White Oak, Maryland campus to solicit feedback and discuss the implementation of two recommendations: the public posting of device photographs and the development of an online labeling repository. Lastly, CDRH may issue device-specific guidance on:</span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">When and what type of manufacturing data to submit</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">When a pre-clearance inspection would be conducted</span></li> <li><span style="font-family: arial,helvetica,sans-serif;">When and what types of modifications should be periodically reported in lieu of submitting 510(k) or </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">When and what type of safety and effectiveness information for the device to be reviewed that is known to the manufacturer should be submitted as a brief description.</span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;">These guidance’s however are on a case-by-case basis, and there is no timeframe for taking action as of now. FDA said it will post updates on the status of planned actions on CDRH’s website.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Issues to Be Referred to the Institute of Medicine </strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">FDA received comments on seven of the recommendations that stakeholders found problematic. As a result, FDA is giving the Institute of Medicine (IOM) an opportunity to provide feedback as part of its independent review of the 510(k) program before FDA makes a final decision. Should the IOM offer comments FDA will take them into consideration. The recommendations are as follows:</span></p> <ul> <li><span style="font-family: arial,helvetica,sans-serif;">CDRH should consolidate the terms “indication for use” and “intended use” into a single term, “intended use”; </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">CDRH should expand its statutory authority to consider off-label use when determining the intended use of a device; </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">CDRH should issue guidance on when a device should no longer be available for use as a predicate; </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">CDRH should issue a regulation on its rescission authority; </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">CDRH should require manufacturers to keep one unit of a device available; </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">CDRH should issue guidance to create a “Class IIb”; and </span></li> <li><span style="font-family: arial,helvetica,sans-serif;">CDRH should seek greater authorities to require postmarket surveillance studies as a condition of clearance for certain devices.</span></li> </ul> <p><span style="font-family: arial,helvetica,sans-serif;"><strong>Discussion</strong></span></p> <p><span style="font-family: arial,helvetica,sans-serif;">As the <a href="http://online.wsj.com/article/SB10001424052748703951704576092051613167570.html">Wall Street Journal</a> noted, the 510(k) changes announced by FDA made key concessions to device makers by putting off several proposed rules that drew fire from the industry. Companies particularly objected to proposed rules that would have enhanced the FDA’s authority to revoke approval of devices and strengthened the agency’s ability to force manufacturers to conduct post-market safety studies.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Both proposals were among the seven that didn’t make the final cut.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">While the 510(k) changes appear to show positive changes for the medical device industry that promote innovation, implementing these changes will take some time, as noted by FDA’s implementation plan. Additionally, as FDA and the IOM consider other proposals and recommendations, uncertainty about other provisions may still cause device makers trouble in predicting future approval and receiving funding and investment.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Nevertheless, it would appear that FDA’s process of listening to the public, industry, and a <a href="http://www.policymed.com/2010/12/15-senators-ask-fda-for-a-501k-process-that-supports-innovation.html">number of policymakers</a> have paid off for the device industry. The new actions released by FDA show a willingness and commitment of the agency to continue encouraging innovation so that America can remain a leader in medical innovation and technology and citizens can continue to have access to the latest devices, while still guaranteeing safety and effectiveness.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">If America wants to lower health care costs and bring better quality and efficiency to our health care system, developing newer medical devices and technologies will be an effective way at achieving this goal. Moreover, now that FDA has given more certainty to the medical device approval process, federal health agencies, academic medical centers, and health institutions should promote more ways for industry and the public to collaborate in bringing new technologies and medical devices to the public.</span></p> <p><span style="font-family: arial,helvetica,sans-serif;">Moving forward, Congress and policymakers need to provide FDA with adequate resources, funding and support to ensure that these initiatives are successful and maintained so that innovation and medical technology only increases.</span></p> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2011/01/fda-updates-510k-approval-process-for-medical-devices.html/feed</wfw:commentRss> <slash:comments>0</slash:comments> </item> <item> <title>Allergan Botox Settlement and Corporate Integrity Agreement</title> <link>https://www.policymed.com/2010/09/allergan-botox-settlement-and-corporate-integrity-agreement.html</link> <comments>https://www.policymed.com/2010/09/allergan-botox-settlement-and-corporate-integrity-agreement.html#respond</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Fri, 03 Sep 2010 01:02:00 +0000</pubDate> <category><![CDATA[HHS-OIG]]></category> <category><![CDATA[Medical Legal]]></category> <category><![CDATA[Pharmaceutical and Device]]></category> <category><![CDATA[$600 Million]]></category> <category><![CDATA[Allergan]]></category> <category><![CDATA[Botox]]></category> <category><![CDATA[consultants]]></category> <category><![CDATA[corporate integrity agreement]]></category> <category><![CDATA[FDA]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[HHS OIG]]></category> <category><![CDATA[NEW]]></category> <category><![CDATA[off label]]></category> <category><![CDATA[onabotulinumtoxinA]]></category> <category><![CDATA[settlement agreement]]></category> <category><![CDATA[third party educational activity]]></category> <category><![CDATA[US Department of Justice]]></category> <guid isPermaLink="false">http://www.policymed.com/allergan-botox-settlement-and-corporate-integrity-agreement/</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="800" height="522" src="https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi.jpg 800w, https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi-300x196.jpg 300w, https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi-768x501.jpg 768w, https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi-210x136.jpg 210w" sizes="auto, (max-width: 800px) 100vw, 800px" /></div>This week, the United States Department of Justice (DOJ) announced that it has reached a resolution regarding the previously reported Government investigation into Allergan’s past U.S. sales and marketing practices relating to certain therapeutic uses of BOTOX(R) (onabotulinumtoxinA), which covered a period that commenced in January of 2000. The company had been cooperating with the […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="800" height="522" src="https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi.jpg 800w, https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi-300x196.jpg 300w, https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi-768x501.jpg 768w, https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f38c54df970b-800wi-210x136.jpg 210w" sizes="auto, (max-width: 800px) 100vw, 800px" /></div><p><span style="font-family: 'Arial', 'sans-serif';">This week, the United States Department of Justice (DOJ) announced that it has reached a resolution regarding the previously reported Government investigation into Allergan’s past U.S. sales and marketing practices relating to certain therapeutic uses of BOTOX(R) (onabotulinumtoxinA), which covered a period that commenced in January of 2000. The company had been cooperating with the Government in a multi-year investigation in Atlanta, Georgia.</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">According to a press release posted on the </span><a href="http://www.justice.gov/opa/pr/2010/September/10-civ-988.html"><span style="font-family: 'Arial', 'sans-serif';"><span style="color: #800080;">DOJ’s website</span></span></a><span style="font-family: 'Arial', 'sans-serif';">, Allergan Inc. has agreed to plead guilty and pay $600 million to resolve its criminal and civil liability arising from the company’s unlawful promotion of its biological product, Botox® Therapeutic, for uses not approved as safe and effective by the Food and Drug Administration (FDA). The resolution includes a <a href="http://www.faqs.org/sec-filings/100901/ALLERGAN-INC_8-K/dex103.htm"><span style="color: #800080;">criminal fine and forfeiture totaling $375 million</span></a> and a <a href="http://www.faqs.org/sec-filings/100901/ALLERGAN-INC_8-K/dex101.htm"><span style="color: #800080;">civil settlement with the federal government and the states of $225 million</span></a>.</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">The civil settlement resolves three lawsuits filed in federal court in the Northern District of Georgia under the qui tam, or whistleblower, provisions of the False Claims Act, which allow private citizens to bring civil actions on behalf of the United States and share in any recovery. The whistleblowers – Dr. Amy Lang, Charles Rushin, Cher Beilfuss, Kathleen O’Conner-Masse, and Edward Hallivis – will receive $37.8 million from the federal share of the settlement amount. </span></p> <p><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif';">Background</span></strong></p> <p><span style="font-family: 'Arial', 'sans-serif';">Under the Food, Drug and Cosmetic Act (FDCA), a company must specify the intended uses of a product in its new drug application to the FDA. Before a drug is approved the FDA must determine that the drug is safe and effective for the use proposed by the company, and once approved, the drug may not be marketed or promoted for off-label uses. Although doctors are permitted to prescribe any approved drug for off-label uses, it is illegal for drug makers to promote medications for any purpose not specifically approved by the FDA. </span></p> <p><span style="font-family: 'Arial', 'sans-serif';">The DOJ’s press release explained that in 1989 the FDA approved Botox®, a prescription biological product containing botulinum toxin type A, a purified neurotoxin, to treat strabismus (crossed eyes) and blepharospasm (involuntary eyelid muscle contraction). In 2000 and 2004, approval was given to treat cervical dystonia (involuntary neck muscle contraction) and primary axillary hyperhidrosis (excessive underarm sweating), respectively. In 2010, approval was given to treat adult upper-limb spasticity.</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">Consequently, Tony West, Assistant Attorney General for the Civil Division of the Department of Justice, and Sally Quillian Yates, U.S. Attorney for the Northern District of Georgia, announced the filing of a criminal information against Allergan for promoting Botox® for headache, pain, spasticity and juvenile cerebral palsy – none of which were approved by the FDA. According to the criminal information, Allergan made it a top corporate priority to maximize sales of Botox® for such off-label uses.</span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';">Settlement</span></strong></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';">Allergan agreed to plead guilty to a single misdemeanor “misbranding” charge covering the period 2000 through 2005 and pay to the Government $375 million. This misbranding charge is known as a strict liability offense, and does not involve false or deceptive conduct. </span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';">As part of its plea, Allergan has agreed that between 2000 through 2005, its marketing of BOTOX(R) resulted in intended uses for the therapeutic treatment of headache, pain, spasticity and juvenile cerebral palsy. These uses were off-label during the relevant time frame and thus the labeling for BOTOX(R) did not bear directions for these intended uses, resulting in the product being misbranded. </span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';">In addition, Allergan has agreed to pay $225 million to resolve civil claims asserted by DOJ under the civil False Claims Act. However, in a </span><a href="http://agn.client.shareholder.com/releasedetail.cfm?ReleaseID=503974"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="color: #800080;">pressrelease</span></span></a><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"> from the company, Allergan denies liability associated with these civil allegations and does not believe there is merit to them factually or legally. </span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';">What was interesting about this settlement is that Allergan was required by the Government to dismiss Allergan’s First Amendment lawsuit pending in Washington, D.C., in which Allergan sought a ruling that it could proactively share truthful scientific and medical information with the medical community to assist physicians in evaluating the risks and benefits if they choose to use BOTOX(R) off-label to treat certain forms of spasticity. </span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';">Allergen Corporate Integrity Agreement</span></strong></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';">The <a href="http://oig.hhs.gov/fraud/cia/agreements/Allerga_Executed_CIA_with_Appendices.pdf"><span style="color: #800080;">Corporate Integrity Agreement</span></a></span> <span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';">Allergan has entered into with the Office of Inspector General of the U.S. Department of Health and Human Services, will require the company to maintain its current compliance program and undertake a series of compliance-related obligations, including additional monitoring, maintenance of specific written standards, auditing, training, education, reporting and disclosure, for five years. The CIA also provides for an independent third-party review organization to assess and report on Allergan’s compliance program. In addition, the CIA provides that:</span></p> <p class="MsoListParagraphCxSpFirst" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;">Sales representatives refer all requests for information about off-label uses of Allergan’s Government Reimbursed Products to its Medical Affairs Department</span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Materials distributed by Medical Affairs in response to requests for information about off-label use must be consistent with applicable FDA requirements;</span></span></p> <p class="MsoListParagraphCxSpLast" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Allergen creates a database to keep track of inquiries for the medical information about off-label uses, such as </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">1) Date of Inquiry; </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">2) Form of Inquiry (<em>e.g., </em>fax, phone, etc.); </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">3) Name of the requesting health care professional (HCP) or health care </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"><span style="mso-spacerun: yes;"> </span>institution (HCI) </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">4) Nature and topic of request (including exact language of the Inquiry if made </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"><span style="mso-spacerun: yes;"> </span>in writing); </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">5) nature/form of the response from Allergan (including a record of the <span style="mso-spacerun: yes;"> </span></span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"><span style="mso-spacerun: yes;"> </span>materials provided to the HCP or HCI in response to the request); and </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">6) The name of the Allergan representative who called on or interacted with </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"><span style="mso-spacerun: yes;"> </span>the HCP or HCI, if known;</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt 0.75in; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">The Policies and Procedures require that<span style="color: black;"> all promotional and written materials and information intended to be disseminated outside Allergan by appropriate qualified personnel:</span></span></span></p> <p class="MsoNormal" style="line-height: normal; text-indent: 0.5in; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoListParagraphCxSpFirst" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l0 level1 lfo2;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">1)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Are given to applicable review committees to review all promotional materials prior to the distribution or use of such materials; and </span></span></p> <p class="MsoListParagraphCxSpLast" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l0 level1 lfo2;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">2)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Deviations from the standard review committee practices and protocols (including timetables for the review of materials) must be documented and referred for appropriate follow-up;</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: Arial;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;">Consultant or Other Fee-for-Service Arrangements</span></strong> </span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Under the CIA, these arrangements with HCPs or HCIs (i.e. speaker programs, speaker training programs, presentations, etc.) and all events and expenses relating to such engagements or arrangements must be designed and used for legitimate and lawful purposes in accordance with applicable Federal health care program and FDA requirements. The Policies and Procedures include requirements about the:</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoListParagraphCxSpFirst" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Content and circumstances of such arrangements and events; and</span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Programs to educate sales representatives, including but not limited to presentations by HCPs at sales meetings and experience-based learning activities, if any.</span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Sponsorship or funding of charitable contributions;</span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Funding of grants (including educational grants) to HCPs and HCIs. </span></span></p> <p class="MsoListParagraphCxSpLast" style="line-height: normal; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: Arial;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;">Third Party Educational Activity</span></strong> </span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">The Policies and Procedures require that: </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoListParagraphCxSpFirst" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l2 level1 lfo3;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">1)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Allergan disclose its financial support of the Third Party Educational Activity;</span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l2 level1 lfo3;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">2)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Allergen disclose any financial relationships with faculty, speakers, or organizers at such Activity; </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l2 level1 lfo3;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">3)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">As a condition of funding, the third party must agree to disclose Allergan’s financial support of the Third Party Educational Activity and any financial relationships that Allergan might have with faculty, speakers, or organizers at such Activity; </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l2 level1 lfo3;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">4)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Any faculty, speakers, or organizers at the Third Party Educational Activity disclose any financial relationship with the applicable Allergan entity; </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l2 level1 lfo3;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">5)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">The Third Party Educational Activity have an educational focus; </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l2 level1 lfo3;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">6)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">The content, organization, and operation of the Third Party Educational Activity be independent of Allergan’s control; </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l2 level1 lfo3;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">7)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Allergan or the Allergan Affiliate support only Third Party Educational Activity that is non-promotional in tone/nature; and</span></span></p> <p class="MsoListParagraphCxSpLast" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 27pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l2 level1 lfo3;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">8)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Allergan’s or any Allergan Affiliate’s support of a Third Party Educational Activity must be contingent on the provider’s commitment to provide information at the Third Party Educational Activity that is fair, balanced, accurate and not misleading;</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">In following these policies, Allergen must ensure that review of all promotional and written materials and information intended to be disseminated outside Allergan by appropriate qualified personnel (such as regulatory, medical, and/or legal personnel) is done in a manner designed to ensure that legal, regulatory, and medical concerns are properly addressed during Allergan’s review and approval process and are elevated when appropriate.</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Monitoring Program</span></span></strong></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">The CIA also requires that Allergan develop and implement a monitoring program, known as the Non-Promotional Monitoring Program, for the following types of activities: </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; text-indent: 0.5in; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">1) Consultant arrangements; </span></span></p> <p class="MsoNormal" style="line-height: normal; text-indent: 0.5in; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">2) Research-related activities; </span></span></p> <p class="MsoNormal" style="line-height: normal; text-indent: 0.5in; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">3) Publication activities; and </span></span></p> <p class="MsoNormal" style="line-height: normal; text-indent: 0.5in; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">4) Medical education grants. </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">With respect to consultant arrangements, research-related activities, and publication activities, the CIA requires that all Consultants, Researchers and Authors, enter written agreements describing: </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoListParagraphCxSpFirst" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">The scope of work to be performed; </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">The fees to be paid; and </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Compliance obligations for the Consultants. </span></span></p> <p class="MsoListParagraphCxSpLast" style="line-height: normal; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">In addition, for each of these activities, the CIA requires that researchers, consultants, and authors be paid based on a fair-market value analysis conducted by Allergan, and that this fair-market value analysis be incorporated into guidelines that are used in the review, approval, and funding of these activities.</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Regarding the monitoring of each of these activities, the CIA establishes that the Monitoring Program must conduct live monitoring for each Reporting Period of:</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoListParagraphCxSpFirst" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">At least 30 Consultant arrangements with HCPs;</span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">At least 10 advisory board programs; </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Monitoring of 20 other professional services agreements with HCPs;</span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">At least 20 Researcher arrangements with HCPs or HCIs;</span></span></p> <p class="MsoListParagraphCxSpLast" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">At least 25 U.S.-sponsored Publication Activities;</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">With regards to medical education grants, Allergan represents that it has established a Medical Education Department within its Medical Affairs Department as the exclusive mechanism through which requestors may seek or be awarded grants for independent medical education activities. Allergan represents that:</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoListParagraphCxSpFirst" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Its sales and marketing departments have no involvement in, or influence over, the review and approval of medical education grants. </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Grant requests must be submitted through an on-line process; and </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Requests are processed in accordance with standardized criteria developed by the Medical Education Department.</span></span></p> <p class="MsoListParagraphCxSpLast" style="line-height: normal; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">The CIA requires that Allergan continue the medical education grant process described above (or an equivalent process) throughout the term of the CIA, and the company must notify the OIG in writing at least 60 days prior to the implementation of any new system subsequent to the Effective Date.</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Additionally, the CIA requires Allergan to establish a Grants Monitoring Program for each Reporting Period to monitor at least 30 medical education grants. The Grants</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Monitoring Program will select grants for review both on a risk-based targeting approach</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">and on a sampling approach. Allergan compliance personnel conducting the Grants</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Monitoring Program will review:</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoListParagraphCxSpFirst" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Proposal documents (including grant requests);</span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Approval documents, contracts, payments, and materials relating to the Medical Education Department’s review of the requests; and </span></span></p> <p class="MsoListParagraphCxSpLast" style="line-height: normal; text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l1 level1 lfo1;"><span style="font-family: 'Times New Roman', 'serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Documents and materials relating to the grants and any events or activities funded through the grants</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">These materials will be reviewed in order to assess whether the activities are conducted in a manner consistent with Allergan’s Policies and Procedures. Results from the Grant Monitoring Programs, including the identification of potential violations of policies, will be compiled and reported to the Corporate Compliance Department for review and follow-up as appropriate.</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;">Physician Payments</span></span></strong></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></strong></p> <p class="Default" style="margin: 0in 0in 0pt;"><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">The CIA also contains specific provisions with respect to payments from Allergen to physicians. The payments are broken into two phases: “Phase I Payments” are defined to include:</span></span></p> <p class="Default" style="margin: 0in 0in 0pt;"><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;"> </span></span></p> <p class="Default" style="text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">All payments or transfers of value (whether in cash or in kind) made by Allergan to physicians and/or to Related Entities related to:</span></span></p> <p class="Default" style="text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">Meals, speaker programs, or advisory boards conducted by Sales, Marketing, or Medical Affairs.</span></span></p> <p class="Default" style="margin: 0in 0in 0pt 9pt;"><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;"> </span></span></p> <p class="Default" style="margin: 0in 0in 11.55pt;"><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">Phase II Payments, include all “</span></span><a href="http://www.policymed.com/2010/03/physician-payment-sunshine-provisions-patient-protection-affordable-care-act.html"><span style="font-family: 'Arial', 'sans-serif';"><span style="color: #800080; font-family: Arial;">payments or transfers of value</span></span></a><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">” as defined by the Patient Protection and Affordable Care Act. The reporting will go as follows:</span></span></p> <p class="Default" style="text-indent: -9pt; margin: 0in 0in 11.55pt 0.25in; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">April 30, 2011, Allergan will begin posting in a prominent position on its website Phase I Reporting during the last two quarters of 2010 and the aggregate value of such Phase I Payments.</span></span></p> <p class="Default" style="text-indent: -9pt; margin: 0in 0in 11.55pt 0.25in; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">August 31, 2011, Allergan will also post on its website a listing of updated information about all Phase I Payments provided during the first two quarters of 2011.</span></span></p> <p class="Default" style="text-indent: -9pt; margin: 0in 0in 11.55pt 0.25in; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">November 30, 2011, Allergan will begin posting Phase II Payments during the third quarter of 2011 and the aggregate value of such Phase II Payments. </span></span></p> <p class="Default" style="text-indent: -9pt; margin: 0in 0in 11.55pt 0.25in; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">After the November 30, 2011 posting, 60 days after the end of each subsequent calendar quarter, Allergan must also post on its website a listing of updated information about all Phase II payments provided during the preceding quarter(s) in each calendar year. </span></span></p> <p class="Default" style="text-indent: -9pt; margin: 0in 0in 0pt 0.25in; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">Beginning on February 29, 2012, and 60 days after the end of each subsequent calendar year, Allergan must post on its website a report of the cumulative value of the Phase II Payments provided to all U.S.-based physicians and Related Entities directly or indirectly from Allergan during the prior applicable calendar year. </span></span></p> <p class="Default" style="margin: 0in 0in 0pt 0.25in;"><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;"> </span></span></p> <p class="Default" style="margin: 0in 0in 11.55pt;"><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">All of the above reporting must be easily accessible and a readily searchable listing of all U.S.-based physicians and Related Entities who or which received Phase I or II Payments directly or indirectly from Allergan. In addition:</span></span></p> <p class="Default" style="text-indent: -13.5pt; margin: 0in 0in 11.55pt 22.5pt; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">Each listing must include a complete list of all individual physicians and Related Entities to whom or to which Allergan directly or indirectly made Payments in the preceding quarter or year (as applicable). </span></span></p> <p class="Default" style="text-indent: -13.5pt; margin: 0in 0in 11.55pt 22.5pt; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">Each listing will be arranged alphabetically according to the physicians’ last name or the name of the Related Entity. </span></span></p> <p class="Default" style="text-indent: -13.5pt; margin: 0in 0in 11.55pt 22.5pt; mso-list: l1 level1 lfo1;"><span style="mso-fareast-font-family: 'Times New Roman';"><span style="mso-list: Ignore;">–<span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">The Payment amounts in the lists will be reported in $10,000 increments (e.g., $0 – $10,000; $10,001- $20,000; etc.) </span></span></p> <p class="Default" style="margin: 0in 0in 11.55pt 9pt;"><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">For each physician, the applicable listing will include the following information: </span></span></p> <p class="Default" style="text-indent: -13.5pt; margin: 0in 0in 11.55pt 31.5pt; mso-list: l3 level1 lfo4;"><span style="font-family: 'Arial', 'sans-serif'; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">i)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">Physician’s full name; </span></span></p> <p class="Default" style="text-indent: -13.5pt; margin: 0in 0in 11.55pt 31.5pt; mso-list: l3 level1 lfo4;"><span style="font-family: 'Arial', 'sans-serif'; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">ii)</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">Name of any Related Entities (if applicable); </span></span></p> <p class="Default" style="text-indent: -13.5pt; margin: 0in 0in 11.55pt 31.5pt; mso-list: l3 level1 lfo4;"><span style="font-family: 'Arial', 'sans-serif'; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">iii)</span> </span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;">City and state that the physician or Related Entity has provided to Allergan for contact purposes; and </span></span></p> <p class="Default" style="text-indent: -13.5pt; margin: 0in 0in 11.55pt 31.5pt; mso-list: l3 level1 lfo4;"><span style="font-family: 'Arial', 'sans-serif'; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">iv)</span> </span></span><span style="font-family: 'Arial', 'sans-serif';"><span style="font-family: Arial;"><span style="mso-spacerun: yes;"> </span>The aggregate value of the payment(s) in the preceding six-month period or year (as applicable). If payments for multiple physicians have been made to one Related Entity, the aggregate value of all payments to the Related Entity will be the reported amount. </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;">On a bi-annual basis, Allergan must post on its company website the following information with respect to both medical education grants and charitable contributions to U.S.-based HCIs: </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoListParagraphCxSpFirst" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l4 level1 lfo5;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">1.</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;">The recipient organization’s name: </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l4 level1 lfo5;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">2.</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;">A brief description of the program for which the grant or charitable contribution was requested; and </span></span></p> <p class="MsoListParagraphCxSpMiddle" style="line-height: normal; text-indent: -0.25in; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l4 level1 lfo5;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt; mso-fareast-font-family: Arial;"><span style="mso-list: Ignore;"><span style="font-family: Arial;">3.</span><span style="font: 7pt 'Times New Roman';"> </span></span></span><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;">The amount of the grant or charitable contribution. </span></span></p> <p class="MsoListParagraphCxSpLast" style="line-height: normal; margin: 0in 0in 0pt 0.5in; mso-add-space: auto; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;">Allergan must continue to post (and provide updates to) the above-described information about medical education grants and charitable contributions to U.S.-based HCIs throughout the term of this CIA. The company must also notify the OIG in writing at least 60 days prior to any change in the substance of its policies regarding the funding of medical education grants and charitable contributions to U.S.-based HCIs or posting of the above-referenced information relating to such funding.</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;">Journals</span></span></strong></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></strong></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;">Allergan represents that it expects all Authors of biomedical manuscripts to fully comply with the International Committee of Medical Journal Editors (ICMJE) criteria regarding authorship and disclosure of their relationship with Allergan and to disclose any potential conflicts of interest, including any financial or personal relationships that might be perceived to bias their work.</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;"><span style="font-family: Arial;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 0pt; mso-layout-grid-align: none;"><span style="font-family: Arial;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; color: black; font-size: 12pt;">Impact of Settlement and CIA</span></strong></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="font-family: Arial;">Douglas S. Ingram, Allergan’s Executive Vice President, noted that “This settlement is in the best interest of our stockholders as it resolves all matters at issue in the investigation, avoids substantial costs of litigation, as well as the substantial risks to Allergan associated with Government enforcement action in these matters, and permits us to focus our time and resources on productively developing new treatments for patients and the medical community.” </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="font-family: Arial;">While the criminal resolution is subject to approval by the federal court in Northern District of Georgia, and the civil settlement is contingent upon such approval, Allergan is disappointed that the court was not afforded an opportunity to hear and rule on the important First Amendment issues, as Allergan believes that physicians, patients, manufacturers, payers, and ultimately the quality of evidence-based medicine itself would have benefited from a ruling clarifying the law. </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="font-family: Arial;">The company also asserted in its press release that “Allergan is committed to conducting its business consistent with high ethical standards and in compliance with all applicable laws.” To meet its compliance goals, Allergan has a robust and regularly reviewed and updated compliance program. The company also noted that it has further enhanced its compliance program by developing additional comprehensive policies and procedures, supported by significant technology investments, including its state-of-the-art Business Execution Automated Compliance Navigator (BEACON) compliance system. </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="font-family: Arial;">1<sup>st</sup> Amendment Suit</span></span></strong></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="font-family: Arial;">As we discussed the government negotiated that Allergan drop their first amendment suit against the Food and Drug Administration. <span style="mso-spacerun: yes;"> </span></span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="font-family: Arial;">First as a citizen of the United States it is disappointing that the government would use their prosecutorial powers to force individuals to withdraw challenging the constitutionality of a law.<span style="mso-spacerun: yes;"> </span>This is something one would expect from a third world country not the world’s greatest constitutional democracy.<span style="mso-spacerun: yes;"> </span></span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="font-family: Arial;">If the FDA does have the right within the constitution to regulate the dissemination of scientifically proven information then they should have no fear in defending that right.<span style="mso-spacerun: yes;"> </span><span style="mso-spacerun: yes;"> </span>With the threat of prosecutions constantly standing over the heads of company directors, it is unlikely that a larger pharmaceutical company would take on the federal government and small companies would never have access to the resources to challenge the law.<span style="mso-spacerun: yes;"> </span><span style="mso-spacerun: yes;"> </span>I am hopeful that some time in the near future someone will take the FDA on in this matter and when they do, it is very likely the FDA will lose on constitutional grounds.<span style="mso-spacerun: yes;"> </span>Otherwise why would the FDA go to all the trouble to get it withdrawn?</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><span style="font-family: Arial;">Key Documents:</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><a href="http://www.faqs.org/sec-filings/100901/ALLERGAN-INC_8-K/dex103.htm"><span style="color: #800080; font-family: Arial;">Criminal Settlement 9/1/10</span></a></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><a href="http://www.faqs.org/sec-filings/100901/ALLERGAN-INC_8-K/dex101.htm"><span style="color: #800080; font-family: Arial;">Civil Settlement 9/1/10</span></a></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><a href="http://oig.hhs.gov/fraud/cia/agreements/Allerga_Executed_CIA_with_Appendices.pdf"><span style="color: #800080; font-family: Arial;">Corporate Integrity Agreement 9/1/10</span></a></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><a href="http://www.faqs.org/sec-filings/100901/ALLERGAN-INC_8-K/"><span style="color: #800080; font-family: Arial;">Form 810K – Securities and Exchange Commission</span></a></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><a href="http://www.justice.gov/opa/pr/2010/September/10-civ-988.html"><span style="color: #800080; font-family: Arial;">Press Release DOJ</span></a></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: 'Arial', 'sans-serif'; font-size: 12pt; mso-fareast-font-family: 'Times New Roman';"><a href="http://agn.client.shareholder.com/releasedetail.cfm?ReleaseID=503974"><span style="color: #800080; font-family: Arial;">Press Release Allergan</span></a></span></p> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2010/09/allergan-botox-settlement-and-corporate-integrity-agreement.html/feed</wfw:commentRss> <slash:comments>0</slash:comments> </item> <item> <title>Milwaukee Journal Sentinel: The Case of BMP-2 Ignoring Any Benefit from Innovation</title> <link>https://www.policymed.com/2010/09/milwaukee-journal-sentinel-the-case-of-bmp-2-ignoring-any-benefit-from-innovation.html</link> <comments>https://www.policymed.com/2010/09/milwaukee-journal-sentinel-the-case-of-bmp-2-ignoring-any-benefit-from-innovation.html#respond</comments> <dc:creator><![CDATA[Thomas Sullivan]]></dc:creator> <pubDate>Wed, 01 Sep 2010 01:55:00 +0000</pubDate> <category><![CDATA[Clinical Research]]></category> <category><![CDATA[FDA]]></category> <category><![CDATA[Innovation]]></category> <category><![CDATA[Media]]></category> <category><![CDATA[Pharmaceutical and Device]]></category> <category><![CDATA[BMP-2]]></category> <category><![CDATA[Bone Graph Substitute]]></category> <category><![CDATA[Food and Drug Administration]]></category> <category><![CDATA[Infuse]]></category> <category><![CDATA[LT Cage]]></category> <category><![CDATA[Medtronic]]></category> <category><![CDATA[Milwaukee Journal Sentinel]]></category> <category><![CDATA[NEW]]></category> <category><![CDATA[Thomas Zdeblick]]></category> <category><![CDATA[University of Wisconsin]]></category> <guid isPermaLink="false">http://www.policymed.com/milwaukee-journal-sentinel-the-case-of-bmp-2-ignoring-any-benefit-from-innovation/</guid> <description><![CDATA[<div style="margin-bottom:20px;"><img width="469" height="360" src="https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f376a3a2970b-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f376a3a2970b-800wi.jpg 469w, https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f376a3a2970b-800wi-300x230.jpg 300w" sizes="auto, (max-width: 469px) 100vw, 469px" /></div>Progress in medicine is essential for discovering new ways to make people healthier, experience less pain, and to live longer. The efforts of countless researchers, physicians, scientists, and patients have led to tremendous breakthroughs and progress in medicine over the past decade and without their collaboration, it would have been difficult to achieve the quality […]]]></description> <content:encoded><![CDATA[<div style="margin-bottom:20px;"><img width="469" height="360" src="https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f376a3a2970b-800wi.jpg" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" alt="" decoding="async" loading="lazy" srcset="https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f376a3a2970b-800wi.jpg 469w, https://www.policymed.com/wp-content/uploads/2010/09/6a00e5520572bb88340133f376a3a2970b-800wi-300x230.jpg 300w" sizes="auto, (max-width: 469px) 100vw, 469px" /></div><p><span style="font-family: 'Arial', 'sans-serif';">Progress in medicine is essential for discovering new ways to make people healthier, experience less pain, and to live longer. The efforts of countless researchers, physicians, scientists, and patients have led to tremendous breakthroughs and progress in medicine over the past decade and without their collaboration, it would have been difficult to achieve the quality of life we enjoy today. In fact, without this process, in which drugs and medical devices are made, tested, and updated, we would never find the treatments that eventually help make our lives better. </span></p> <p><span style="font-family: 'Arial', 'sans-serif';">A recent article from the </span><a href="http://www.jsonline.com/features/health/101732913.html"><span style="font-family: 'Arial', 'sans-serif';"><span style="color: #800080;">Journal Sentinel</span></span></a><span style="font-family: 'Arial', 'sans-serif';"> however, undermines this collaboration between researchers, patients, and industry by pointing to a group of physicians involved in a powerful new biological agent that promised to revolutionize back surgery, and suggesting that financial motivations created conflicts of interest. <span style="mso-spacerun: yes;"> </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: Arial;"><span style="mso-bidi-font-size: 12.0pt; mso-bidi-font-family: Arial;">The drug in question, known as Infuse, “was like nothing the burgeoning field of spinal fusion surgery had seen before because it turned whatever it touched into bone.” As the Sentinel explained, </span><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;">the “treatment consists of a tapered, metallic fusion cage that looks like a thimble and the BMP-2 bone graft substitute. The substitute, which is placed inside the LT-Cage, includes the genetically engineered human protein (BMP-2) that is placed on an absorbable sponge. The LT-Cage maintains spacing between the vertebrae while the BMP-2 generates the formation of new bone in order to permanently stabilize that section of the spine.” </span></span></p> <p><span style="font-family: 'Arial', 'sans-serif';">For the Sentinel, “the story of BMP-2 raised questions about whether doctors should be allowed to do clinical trial research involving products that might enrich them or the company they work for.” What the Sentinel completely ignores are questions about the positive impact BMP-2 has had on patient’s lives, and the benefits enjoyed by patients who chose this treatment over more painful options. This omission is troubling, considering the author himself admits that despite a risk of leaking out, if BMP-2 is properly “confined to the tiny space between vertebrae, it proved as an effective treatment.”</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">If a treatment is effective, and helps patients, then of what concern should there be about doctors enriching themselves, when patients are benefiting? Shouldn’t their hard work, dedication, investment, and the risks they are taking be adequately rewarded?</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">The Sentinel examines BMP-2 mainly because of the outcome of an advisory meeting panel in January 2002, which happened prior to the drugs approval. Specifically, the Food and Drug Administration (FDA) panel did not address panel member Stephen Li’s issues with the fact that nine doctors who had a financial stake in the product had test results with it that were nearly twice as good as the doctors who did not have a financial interest.</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">Consequently, the FDA panel deferred Li’s concerns to Medtronic, the company that was making Infuse. Explaining what happened next, Marybeth Thorsgaard, a spokeswoman for Medtronic clarified that “the company fully disclosed the success rates of the doctors with financial ties to the company to the FDA.” In fact, Markham Luke, chief medical officer in the FDA’s device evaluation office, noted that in approving the product, the FDA took into account the conflicts of interest of the investigators.</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">As a result, with this information in hand, the panel “probed the issue and made its recommendation to the FDA, which ultimately approved the product.” FDA also said “the package label for BMP-2 covers all safety concerns that the FDA believes the public needs to know.”</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">This cooperation thus showed Medtronic’s strong commitment to preventing the promotion of its products for unapproved uses and its implementation of corporate policies and training to prevent that. </span></p> <p><span style="font-family: 'Arial', 'sans-serif';">Despite the commitment from Medtronic, the Sentinel believes that “the eventual approval of Infuse represented “a familiar playbook,” in which first, a buzz is created about a potential new therapy. As the Sentinel claimed, the next step is for “research – often by doctors with financial ties to the product – to be presented to the FDA for a specific use in a narrow group of people.”</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">The playbook then is that “once the product is on the market, other uses for it are promoted in articles and presentations, often by doctors with financial ties to the company.” But nothing is illegal about these presentations or articles. In fact, the physicians who provide these service help thousands of physicians across the country learn about new treatments and therapies such as Infuse.</span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: Arial;"><span style="mso-bidi-font-size: 12.0pt; mso-bidi-font-family: Arial;">For example, </span><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;">BMP jumped from being used in less than 1% of all fusions in 2002 to being used in 25% in 2006. While the Sentinel claims that much of this increase was fueled by “off-label” use, they also correctly acknowledge that such use is “not illegal for doctors, including those with financial ties to such companies.” </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;"><span style="font-family: Arial;">It seems like the issue the Sentinel takes with the use of BMP was that there is “a considerable amount of evidence suggesting that many patients with back pain do just as well over time without” the BMP surgery. Going on this claim, they assert that “spinal fusion is a controversial treatment for degenerative disc disease,” even though they admit it is an “effective treatment.” </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;"><span style="font-family: Arial;">One would expect that for a treatment to be classified as controversial, it would have a negative success rate however, the FDA noted when approving the product that “the expected overall success for Infuse is 57.1%.” <span style="mso-spacerun: yes;"> </span>So what if fusion without using BMP-2 had a 56.7% success rate? What is the problem with having two treatments effectively treat a particular condition? Why should we be giving patients and doctor’s only one choice?</span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;"><span style="font-family: Arial;">The reality is, spinal fusion surgery in the past “often required harvesting a small amount of bone from the hip, which can be painful and add time to the surgery.” When BMP was being developed, it held the potential to eliminate that pain and additional time for surgery, and still does. </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;"><span style="font-family: Arial;">What the Sentinel is really concerned about is that since the FDA approved the use of BMP for a single-level fusion involving the lumbar spine in which the operation was done from the front, “doctors have been using it off-label in surgical approaches from the back rather than the front, and on the cervical spine as well as the lumbar spine.” To support this claim, the author cites a recent study, which “found a fourfold increase in the use of all BMP products in five years, from 24,000 procedures in 2003 to 103,000 in 2007.” </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;"><span style="font-family: Arial;">Of that increase, the study asserted that “about 85% was off-label use.” But as we discussed above, it is not illegal for doctors, including those with financial ties to companies, to prescribe off-label. Accordingly, the fact that BMP has been used off-label increasingly is a positive affect because without its approval, the many uses it is now being used for would still be without effective treatment. It should be noted however, that physicians using BMP for off-label purposes should advise there patients as such. </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: Arial;"><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;">The Sentinel also takes issue with BMP because despites its approval by FDA,</span><span style="mso-bidi-font-size: 12.0pt; mso-bidi-font-family: Arial;"> “early concerns about its widespread, unapproved use and adverse reactions in patients have materialized.” The article points to “studies that have warned that it can cause life-threatening swelling in the neck, form bone in unwanted locations and possibly fuel the growth of cancer cells or spark adverse immune system reactions.” But the likelihood or possibility of these risks are not discussed, and are specifically not put into the context of the benefits BMP provides. </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;"><span style="font-family: Arial;">Any surgery is going to be risky and expensive, and the fact the surgeons who are conducting these surgeries helped create, study and develop the devices and treatments through industry sponsorship is reassuring. It means that their experience and exposure to the products being used is unmatched. </span></span></p> <p><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif';">New Therapy</span></strong></p> <p><span style="font-family: 'Arial', 'sans-serif';">Consequently, what brought BMP into the media was the fact that Medtronic is now back before the FDA seeking approval for a different BMP-2 product for use in back surgery. The drug, known as Amplify, was considered by an FDA panel last month, in which “concerns about cancer, immune reactions and effectiveness were raised. </span></p> <p><span style="font-family: 'Arial', 'sans-serif';">Accordingly, the Amplify clinical trial, which involved 463 patients, was completed in 2009. It was noted that of 63 surgeons, twenty-seven who operated on more than half of the patients in the clinical trial had a financial interest in Medtronic at the time of the research. Despite what some feel appears to be a conflict, “Medtronic maintained that because the financially connected surgeons had results that were similar to those who did not have such conflicts, their financial interest in Amplify’s success did not affect the results of the trial.”</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">But the Sentinel still wants to drag Amplify under the bus by suggesting that prominent surgeons, such as Thomas Zdeblick, who helped study BMP-2, have conflicts of interest because of their financial ties to Medtronic. The fact that he holds patent rights to a key component of the product and has received more than $22 million dollars in royalties and other payments from Medtronic since 2002 does not represent a “conflict.” It represents the fair market compensation anyone would expect for the work and dedication he endured to help advance this science.</span></p> <p><span style="font-family: 'Arial', 'sans-serif';">Just because a physician earns income from his discoveries does not translate that they are somehow unethical as the Sentinel would have one believe.<span style="mso-spacerun: yes;"> </span>Inventors of all kinds of products every day wake up with the hope that they are creating something that will help others.<span style="mso-spacerun: yes;"> </span>If the products don’t work, people won’t buy them, doctors won’t use them and they won’t get receive income from their failed inventions.<span style="mso-spacerun: yes;"> </span>But if they are successful they should reap some reward so they are incentivized to invent the next beneficial product.</span></p> <p><strong style="mso-bidi-font-weight: normal;"><span style="font-family: 'Arial', 'sans-serif';">Conclusion</span></strong></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="mso-bidi-font-family: Arial;"><span style="font-family: Arial;">Since May of this year, </span></span><a href="http://www.policymed.com/2010/06/physician-payment-sunshine-medtronic-reports-physician-payments.html"><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;"><span style="font-family: Arial;">Medtronic</span></span></a><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;"><span style="font-family: Arial;"> joined several drug companies in publicly listing payments to doctors – in advance of federal legislation that mandates such reporting beginning in 2013. Using this list only for purposes of criminalizing the collaboration of physicians with industry, the Sentinel points out only that “several of the doctors on that list are the same ones who wrote articles about the original Infuse clinical trial or who wrote about off-label uses for BMP-2.” </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;"><span style="font-family: Arial;">This characterization completely ignores the services and benefits created by the doctors. It does not go to explain the teaching or training impact it has had on other physicians, or the better outcomes and education patients will have when they learn about new treatments. Moreover, the Sentinel does not address the level of transparency and its effect on giving the public a greater sense of trust and integrity in Medtronic for disclosing such payments. </span></span></p> <p class="MsoNormal" style="line-height: normal; margin: 0in 0in 10pt; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="font-family: Arial;"><span style="mso-bidi-font-family: Arial;">Instead, critics of this kind of collaboration maintain that when </span><span style="mso-bidi-font-size: 12.0pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: Arial;">information comes from the manufacturers and people who are very vested in the product, the information is tainted, and it creates a conflict. But this claim is misguided.</span></span></p> <p><span style="font-family: 'Arial', 'sans-serif';">Collaboration between physicians and industry remains absolutely vital to innovation in the medical technology industry. While some may believe the BMP-2 story highlights doctors being too “cozy” with industry, the reality is, the product is a success story in treating patients with back problems.</span></p> ]]></content:encoded> <wfw:commentRss>https://www.policymed.com/2010/09/milwaukee-journal-sentinel-the-case-of-bmp-2-ignoring-any-benefit-from-innovation.html/feed</wfw:commentRss> <slash:comments>0</slash:comments> </item> </channel> </rss>