The Food and Drug Administration Safety and Innovation Act (FDASIA): Summary of GDUFA, MDUFA, BsUFA and Pediatrics

The Food and Drug Administration Safety and Innovation Act (FDASIA), signed into law on July 9, 2012, 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.  Below is a brief summary of some of the major provisions contained in FDASIA, provided by various pages on FDA’s website. 

Generic drug User Fee Act 

With the enactment of the Generic Drug User Fee Act (GDUFA), for the first time ever, FDA will receive funding from the generic drug industry to ensure Americans have timely access to safe, high-quality, and effective generic drugs.    

This legislation comes at a critical time — the public health success of generic drugs has also created a significant challenge.  Due to limited resources, FDA has not been able to keep pace with an increasing number of applications requiring review.  There is currently a backlog of more than 2,500 applications for new generic drugs seeking approval.  However, with this new legislation, FDA will now have the needed resources and staff to eliminate this backlog and bring an increased number of generic drugs to the market and into the hands of patients more quickly. 

Benefits to Americans:

• Access – GDUFA will expedite the availability of low-cost, high-quality generic drugs by bringing greater predictability and timeliness to the FDA review process. The current median time for review of a new generic drug application is 31 months.  With GDUFA, FDA expects this review time to drop to 10 months, accelerating the delivery of lower-cost generic products to American consumers and expanding access. 
• Quality – GDUFA will help increase the safety and quality of the drugs Americans receive by assuring that foreign and domestic generic drug manufacturing facilities are held to the same consistent, high-quality standards, and are inspected once every two years, using a risk-based approach.  Currently, FDA only has resources to conduct inspections of foreign generic drug manufacturers about once every 7 to 13 years.
• Transparency – Under GDUFA, all facilities involved in the manufacture of generic drugs and their ingredients, both domestic and foreign, must be identified.  This identification system is critical for enhancing transparency and helping FDA protect Americans in today’s complex global supply environment. 

Benefits to Industry:

• GDUFA will deliver greater predictability and timeliness to the review of generic drug applications, slashing review times and saving industry time and money.
• The Act, based on an agreement negotiated by FDA and representatives of the generic drug industry, reinvigorates and modernizes the generic drug program, sets performance goals, and holds FDA accountable to Congress through annual reports.
• GDUFA fees are estimated to cost the generic drug industry less than ten cents for the average generic prescription.
• The annual fee total for GDUFA represents only about one half of 1 percent of generic drug sales.  This relatively small cost to the industry could be offset by faster review times that bring products to market sooner.

 GDUFA Performance Goals and Efficiency Improvements:

• During the five-year period from fiscal year 2013 through 2017, the generic drug industry will provide FDA an inflation-adjusted $299 million each year in user fees, supplementing the Agency’s allotted budget for assessing the safety of generic drugs.
• Application Metrics – By the fifth year of the program, FDA will review and act on 90 percent of complete electronic generic applications within 10 months after the date of submission.  Certain amended applications may have different metrics, phased in between three and five years.
• Backlog Metrics – FDA will review and act on 90 percent of the generic applications pending on October 1, 2012 within the next five years.
• Inspection Metrics – FDA will aim to achieve risk-adjusted biennial inspections and parity of inspection coverage between foreign and domestic firms in five years.
• Efficiency Enhancements – FDA has made an immediate commitment to provide timely and complete information to applicants by issuing response letters for all abbreviated new drug applications.  Other efficiency enhancements include rolling review, division-level deficiency review, first cycle meetings and a number of regulatory science initiatives. 

Regulatory Science – GDUFA will help advance “regulatory science,” a discipline which seeks to create new tools, standards, and approaches for use in assessing the safety, effectiveness, quality, and performance of products. FDA regulatory science initiatives under GDUFA will include:

• Continue development of new bioequivalence methods for orally inhaled, topical dermatological and gastro-intestinal drug products.
• Continue development of science-based recommendations for product development, and post-marketing assessments of generic drug products.
• Identify additional initiatives with input from an industry working group.

 

Medical Device User Fee Amendments of 2012 

Congress recently authorized the Medical Device User Fee Amendments of 2012 (MDUFA III) as part of FDASIA.  MDUFA III will take effect on October 1, 2012 and will sunset in five years on October 1, 2017. 

Device user fees, first established by Congress in 2002, are paid to FDA by medical device companies when they register and list with the FDA, and when they submit an application or notification to market a medical device in the U.S.  (Other parts of the legislation renewed user fees for the review of drug applications.)  Ultimately, MDUFA III represents a commitment between the U.S. medical device industry and the FDA to increase the efficiency of regulatory processes in order to reduce the time it takes to bring safe and effective medical devices to the U.S. market. 

 MDUFA III is the result of more than a year of public input and negotiations with industry representatives and patient and consumer representatives.  Under MDUFA III, the FDA can collect $595 million (plus adjustments for inflation) in user fees over five years.  With the additional funding, the FDA will be able to hire more than 200 full-time-equivalent workers by the time MDUFA III expires in five years.  

In exchange, the FDA has committed to meet certain performance goals outlined in the  Secretary’s letter to Congress (MDUFA III letter).  For example, in fiscal year (FY) 2013, the FDA will issue a decision about whether or not to allow marketing for 91 percent of 510(k) submissions within 90 days.  As provided in the MDUFA III letter, an outside consulting firm will evaluate FDA’s pre-market review process and the agency’s progress in meeting these goals, including timely interactions with industry. 

Key Facts

• User Fees: MDUFA III authorizes $595 million in user fees for FY 2013-2017. It expands the definition of the types of manufacturers that must pay a registration fee.
• Performance Goals: The MDUFA III letter includes performance goals for decision-making on a variety of application types.  Certain performance goals increase each year of the MDUFA III program.
• Public Reporting: As specified in the MDUFA III letter, CDRH is to provide quarterly reporting of its progress towards meeting specific performance goals, including those for decision-making.  CDRH is also to provide annual reporting about how funding is being used for the device review process.
• Improved Review Experience: The MDUFA III program is expected to result in greater accountability, predictability, and transparency for industry through a more structured pre-submission process, earlier interactions between the FDA and device applicants, and more communication during review.
• Independent Assessment of Pre-market Review Process: An independent consulting organization will evaluate FDA’s pre-market review program and recommend improvements. 

Outcome:  Process Improvements 

The FDA and the medical device industry are committed to protecting and promoting public health by providing timely access to safe and effective medical devices.  The MDUFA III letter outlines process improvements that will help achieve this goal by clearly delineating expectations for FDA and Industry. 

• Improved Pre-Submission Process: In order to make FDA processes more predictable for industry, the FDA will introduce a more structured approach to address product-specific questions regarding review issues for Investigational Device Exemptions (IDEs), 510(k)s and PMAs prior to submission of an application.  Industry will be able to request early FDA feedback on their pathway to marketing through the pre-submission process. 
• Submission Acceptance Criteria: To make the pre-market review process more efficient, the FDA will implement revised submission acceptance criteria through a new draft and then final guidance.  The guidance will include objective criteria for updated refuse to accept/refuse to file checklists to evaluate applications when they are received to ensure that FDA resources are focused on complete applications.  These checklists will go into effect once the final guidance is published. 
• Interactive Review: The FDA continues to encourage and is committed to continuing informal communication between FDA staff and device applicants to collect additional information and meet review timelines.  The MDUFA III letter reaffirms this commitment to these interactions.
• Guidance Document Development: MDUFA III user fees will support FDA’s development of guidance documents, published on FDA’s website, which represent the FDA’s current thinking on a topic.  Guidance is often written to help industry develop pre-market submissions that meet regulatory standards.  Under the MDUFA III program, the FDA will build an improved process for tracking guidance and will communicate the priority list of topics for guidance development. 
• Third-Party Review: The third-party review program is intended to improve the efficiency and timeliness of the FDA’s 510(k) review processes for specific device types by having an accredited third party reviewer conduct the primary review of a 510(k) and submit it to the FDA for final determination.  MDUFA III supports reauthorization of the existing third-party program.
• Patient Safety and Risk Tolerance: The FDA will fully implement final guidance on the factors to consider when making benefit-risk determinations in medical device premarket review.  This guidance focuses on factors to consider in the pre-market review process, including patient tolerance for risk, magnitude of the benefit, and the availability of other treatments or diagnostic tests.   Over the period of the MDUFA III program, the FDA will meet with patient groups to better understand and characterize the patient perspective on disease severity or unmet medical need.  In addition, FDA will increase its utilization of its Patient Representatives as Special Government Employee consultants to provide patients’ views early in the medical product development process and ensure those perspectives are considered in regulatory discussions.
• Emerging Diagnostics: Under the MDUFA III program, the FDA will work with industry to develop a transitional In Vitro Diagnostics approach for the regulation of emerging diagnostics. 

Outcome:  Strengthening FDA Infrastructure 

Performance goals outlined in the MDUFA III letter challenge the FDA to meet new milestones for pre-market review of medical devices and require an investment in staff and technology.  User fees will provide the FDA with the resources necessary to retain, train, and acquire employees with the expertise required to meet these goals and update its information technology to assist in meeting the performance goals. 

• Staffing and Training: User fee revenue will help to reduce the ratio of review staff to front-line supervisors in the pre-market review program and to enhance and supplement scientific review capacity by hiring device application reviewers and leveraging external experts needed to assist with the review of device applications.  In addition, the FDA will be able to provide critical training programs to certify reviewers and educate FDA staff on the requirements in MDUFA III. 
• Tracking: Performance goals in the MDUFA III letter involve tracking of application types, review milestones and tracking of guidance documents in order to report out at specified intervals.  The FDA will continue efforts to improve its information technology systems to support future capability for real-time status of submissions.

 

Pediatric Provisions 

FDASIA renews and strengthens three essential laws to improve the safety and effectiveness of pediatric drugs, biological products, and medical devices used in children: the Best Pharmaceuticals for Children Act (BPCA), the Pediatric Research Equity Act (PREA), and the Pediatric Medical Device Safety and Improvement Act.

Children have unique needs for medical products and these provisions increase the FDA’s ability to meet these needs.  By making BPCA and PREA permanent – no longer subject to reauthorization every five years – the law ensures that children will have a permanent place on the agenda for drug research and development. 

FDASIA requires earlier pediatric study plan submission by drug manufacturers subject to PREA and gives FDA new authority to help ensure PREA requirements are addressed in a more timely fashion.  These improvements will help spur pediatric drug development and speed pediatric drug information to patients and providers. 

To address continuing needs for neonatal expertise, the Act requires the Office of Pediatric Therapeutics to include a staff member with expertise in a pediatric subpopulation that is less likely to be studied under BPCA or PREA and specifies that for five years after enactment, this should include an expertise in neonatology.  It further specifies that an FDA employee with expertise in neonatology should sit on the Pediatric Review Committee.  FDASIA also requires BPCA requests for pediatric drug studies to include a rationale for not including neonatal studies if none are requested. 

For pediatric studies submitted under BPCA 2002 for products granted pediatric exclusivity and receiving a pediatric labeling change, FDASIA requires FDA to post the medical, statistical, and clinical pharmacology reviews and corresponding written requests on the FDA website in the same manner as currently posted materials. (Previously, only medical and clinical pharmacology summaries were required to be posted for these products.)  
 
FDASIA also requires FDA hold a public meeting and to issue a report on efforts to accelerate development of products for pediatric rare diseases.

 

Biosimilars 

With the enactment of the Biosimilar User Fee Act (BsUFA), FDA will receive funding from the biopharmaceutical industry to help ensure Americans have timely access to biological products that have been demonstrated to be “Biosimilar” to an FDA-approved biological product.  Biosimilars are biological products that are highly similar to, or interchangeable with, an already approved biological product.  The approval pathway for biosimilar biological products was authorized by the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), which was intended to create price competition in the biologic drug marketplace.  BsUFA, which establishes a new user fee program for biosimilars, authorizes user fees to support the review of marketing applications for biosimilar biological products. 

The BPCI Act is similar in concept to the Drug Price Competition and Patent Term Restoration Act of 1984 (a.k.a., the “Hatch-Waxman Act”), which enables approval of generic drugs based on their comparison to already approved drugs.  Since 1984, FDA has approved more than 8,000 generic drugs resulting in hundreds of billions of dollars in cost savings to U.S. consumers.  

Currently there are very few therapeutic alternatives to biological products, which are difficult to characterize because they are composed of highly complex molecules, sometimes hundreds of times larger than those of many other drugs.  

Prior to being enacted into law, the provisions in the BsUFA legislation were, as directed by Congress, developed in consultation with  companies that intend to make biosimilar products, patient and consumer advocates, health care professionals, and other public stakeholders.  The law authorizes BsUFA funding for a five year period.  The user fee funding from manufacturers provides FDA with supplemental funding for the agency to hire new staff and to set and implement agency processes to review and approve biosimilar versions of already-approved biological products. 

Benefits to Americans:

• Marketplace competition leading to potentially lower cost alternatives: The approval pathway for biosimilar biological products can lead to marketplace competition and thereby help create less costly alternatives to the biological products currently on the market.  BsUFA funding, which will provide the agency with increased resources to review biosimilar biological product applications and provide feedback to companies seeking to develop biosimilar products, will help speed biosimilars to market.
• Enhanced product access and consumer choice:  BsUFA funding, in providing FDA with increased resources to review biosimilar applications and provide feedback to sponsors, can help drive the development of multiple biological products to treat the same condition.  If there is only one biological product available to treat a certain condition and there becomes an availability issue with that product, for instance a manufacturing problem that limits or stops production, patients who need treatment with that product might not be able to receive adequate therapy.  The development of biosimilars creates the potential for multiple biological products available to treat a condition and thereby the potential for more access to biological products and more consumer choice.  

Benefits to Industry:

• Support to develop effective approval methods.  To generate an efficient approval process for biosimilars, FDA must expend significant resources in evaluating research and protocols for reviewing biosimilar applications and establishing the appropriate scientific methods necessary to help ensure that a biosimilar product will indeed be similar enough to an existing biological product.  BsUFA funding will provide FDA with the necessary resources to enable the development of this important process.
• Business development.  Biosimilars user fees have been designed to be distributed evenly and fairly across the biologic drug industry.  The biologic drug industry has been supportive of these fees as a means of developing and implementing a process within FDA that can lead to enhanced opportunities for new product development and therefore serve as a benefit to their business. 
• Greater predictability.  In exchange for user fees from industry, FDA must strive to reach certain goals of efficiency in terms of the time it takes to review applications for biosimilar biological products.  This provides manufacturers a higher degree of predictability in assessing when FDA will complete a review of their applications for biosimilars.  These goals include targets for FDA to review 70% of applications for biosimilars within 10 months of receipt in fiscal years 2013 and 2014, 80% in fiscal year 2015, 85% in fiscal year 2016 and 90% in fiscal year 2017. There are many other performance goals for FDA set forth in BsUFA, such as goal timeframes for holding meetings with manufacturers with biosimilar biological products in development.