FDLI 2013: Insights in Enforcement, Litigation & Compliance for Pharmaceutical and Medical Device Manufacturers

The Food and Drug Law Institute (FDLI) recently held its annual Advertising & Promotion Conference, which included in-depth presentations, discussions and updates from various government officials and industry insiders regarding interesting cases, new policies and guidance, and enforcement actions and criminal investigations.

Representatives from all four of FDA’s medical product centers (CBER, CDER, CDRH, and CVM), the U.S. Department of Health and Human Services Office of the Inspector General, the U.S. Department of Justice Consumer Protection Branch, and the Federal Trade Commission provided attendees with the latest information on policy and enforcement activities and recommendations for approaching “gray areas” of advertising and promotion.

Policy & Medicine attended the FDLI meeting and Author/Editor Thomas Sullivan presented during the second day of the conference regarding the Physician Payment Sunshine Act, with a particular focus on indirect and third-party payments. Below is a summary of several presentations and discussions from this year’s conference.

Advertising & Promotion Enforcement: Year in Review

Joy Liu, Partner at Ropes & Gray, LLP, presented on major industry settlements over the past year, listing the companies and government offices involved, allegations, and amount settled. She went into greater depth about several cases, including the recently dismissed and settled Par case, the ISTA and Xibrom case, the Wyeth Rapamune case, and the recently filed Novartis case. We have covered three of the previous cases, but have not gone into detail about the Wyeth case.

Liu explained that Rapamune (sirolimus) was approved by FDA in 1999 and indicated as an immunosuppressive drug in renal (kidney) transplant patients. It was also approved for use in conjunction with cyclosporine and corticosteroids. In 2002, FDA added a boxed warning regarding use in liver transplants, stating that such use had not been established as safe and effective and was therefore not recommended. A second boxed warning to the same effect was added in 2003 regarding lung transplants.

Despite these warnings, Liu noted that Wyeth, which was acquired by Pfizer in 2009, used training materials with its sales representatives that included chapters on heart and liver transplantation. The reps trained to use slide decks regarding off-label uses and there were “journal clubs” on recently published articles involving non-renal transplant patients. Documents also showed that sales reps were trained on “openers” to market conversion to transplant surgeons.

Sales reps also received incentive compensation and Wyeth established sales targets that reps “could only achieve by selling for off-label uses”—and 90% of sales in 2007 were alleged to be for off-label uses.

In addition, government investigation revealed that sales directors encouraged their reps to maintain “handwritten business plans” instead of entering plans into the company’s computer system.

The investigation also revealed that experts who were non-renal transplant surgeons were invited to participate in advisor boards or in “Investigator Originated Protocols,” and some non-renal transplant surgeons were retained to speak on non0renal uses at national and local professional meetings.

Additionally, allegations showed that management was involved in this off-label promotion, including marketing and business plans in 2006 to call on non-renal physicians as well as the use of monthly reports of reps who engaged in promotion for non-renal use as “models” for other reps. Management also praised reps for successful off-label promotion “even after” Wyeth’s legal department directed reps not to promote off-label.

The case finally settled at the end of July 2013 for $490.9 million with the U.S. Department of Justice. Wyeth pleaded guilty to a criminal information charging it with a misbranding violation under the FDCA.

Pfizer is currently subject to a Corporate Integrity Agreement (CIA) with the Department of Health and Human Services’ Office of Inspector General that it entered in connection with another matter in 2009, shortly before acquiring Wyeth.  The CIA covers former Wyeth employees who now perform sales and marketing functions at Pfizer.  Under the CIA, Pfizer is subject to exclusion from federal health care programs, including Medicare and Medicaid, for a material breach of the CIA, and the company is subject to monetary penalties for less significant breaches.

“We are committed to enforcing the laws protecting public health, taxpayers and government health programs, and to promoting effective compliance programs,” said Daniel R. Levinson, Inspector General, Department of Health and Human Services.  “Our integrity agreement with Pfizer, which acquired Wyeth, includes required risk assessments, a confidential disclosure program, and auditing and monitoring to help prospectively identify improper marketing.”

HHS-OIG and CIA’s

Several speakers presented on updates regarding HHS-OIG’s recent settlements and CIAs, including a member from the Office of Counsel to the HHS-OIG, Mary Riordan, who noted that OIG’s role in health fraud cases is to “provide investigative support.” Typically, OIG is involved in most False Claims Act cases involving HHS programs and works closely with DOJ. Riordan’s discussion focused on several recent cases that had different types of resolutions (many of which we have previously covered and some that were noted above).

Riordan noted that in addition to OIG’s power of exclusion and CIA’s, the U.S. Department of Justice has “non-monetary” requirements such as requiring companies to submit certifications and reports and affirmative compliance requirements included in plea agreements.

With respect to CIA’s, Riordan noted that the recent focus has been on financial incentives used by companies to enhance or carry out illegal or improper activities, such as incentives to executives and sales representatives. To address these issues, CIA’s focus on holding a company’s board accountable and involved through training and annual resolutions that the board must adopt.

Additionally, Riordan discussed CIA requirements regarding the inclusion of existing internal monitoring activities—one’s that companies had begun prior to entering into their CIA—and a focus on centralized risk assessment programs (e.g., risk assessment, identification, monitoring and mitigation).

In addition to OIG’s presentation, Kirke Weaver, Managing Counsel at Merck & Co also discussed risk assessment in CIA’s. Weaver explained that risk assessments are systematic approaches to identify individual and comparative risks as well as an overall risk profile. Risk assessments are accomplished by identifying and analyzing key potential compliance risks areas, along with plans and controls to mitigate identified areas.

Weaver noted that risk assessments are somewhat of a “new” trend, with four recent CIAs (Abbott, Amgen, GSK, and Par) including them; although Pfizer had this requirement back in 2009 as well (however, that was its second CIA). These risk assessments are often “tailored to company practices” rather than using boilerplate language. He noted that common elements of risk assessment plans include:

• Proactively analyze and address risks for government reimbursed products
  
• Central focus on sales and marketing practices
  
• Cross-functional participation;
  
• A process to uncover and assess risks, including “formal risk ranking”; and
  
• Risk Mitigation Plans, which include
  
  • Listing of monitoring and mitigation activities;
    
  • Tracking and reporting (e.g., physician payments)
    
  • Responsible person for each activity; and
    
  • Dates of completion
    

Weaver than focused on identifying the particular risks associated with sales and marketing. He recommended three main areas of focus. First, the product; companies must know the limitations and complexities of the drug being marketed or sold (e.g., FDA approved indications.

Second, how the product fits into the larger company environment, both from a resources and performance perspective. Finally, how the product fits within the external environment (e.g., competition) and whether the product is subject to external investigations or enforcement activity (e.g., opioids or antipsychotics).

Ultimately, Weaver noted that companies have made several changes as required by and in response to CIAs, such as

• Increased compliance messaging to employees;
  
• Enhanced training
  
• New internal guidance documents or job aides
  
• Internal audits or increased monitoring
  
• Additional approvals or certifications; and
  
• Modifications to or limitations of promotional programs
  

Weaver concluded by noting that there is not one “right” approach to compliance, and that checklists are not the trend. Rather, compliance must by a “proactive process.”

Compliance for Drugs and Biologics Products

During this panel, the discussion focused on challenges and recommendations for industry. Seth Whitelaw, Director, Governance, Regulatory and Risk Strategies at Deloitte noted that increased FDA enforcement of Company Core Data Sheet compliance, off-label marketing, label compliance, and constant changes to labeling format and content requirements by FDA has resulted in increasing level and frequency fines and other enforcement action.

Internally, companies have been focused on:

• Preventing advertising and promotional materials from addressing efficacy based on unsubstantiated evidence and comparative claims, minimizing risk information, and promoting unapproved uses of company’s product
  
• Supporting a balanced presentation of products’ risk and benefit profile on the company’s internet and social media portals
  
• Managing compliance is becoming more challenging as companies enter more markets and rely increasingly on contracted and joint venture partners
  

Externally, competitors & watchdog groups (e.g., ProPublica) have been reporting product materials and promotions, which are expressing off-label claims and usage to the FDA’s Office of Prescription Drug Promotion (OPDP).

Daniel Kracov, Partner at Arnold & Porter, LLP, gave a presentation on the best practices for using health care economic information in advertising and promotion. Kracov noted that recent FDA regulatory letters have focused on economic comparisons that falsely imply product interchangeablity.

Health care economic information first appeared in the Food and Drug Administration Modernization Act (FDAMA), Section 114, which provides that such information may be provided to a formulary committee or other similar entity, in the course of the committee or the entity carrying out its responsibilities for selection of drugs for managed care or other similar organizations. This information will not be considered false or misleading under if the health care economic information directly relates to an indication approved under section 505 or under section 351(a) of the Public Health Service Act for such drug and is based on competent and reliable scientific evidence.

Health care economic information includes “Any analysis that identifies, measures, or compares the economic consequences, including the costs of the represented health outcomes, of the use of a drug to the use of another drug, to another health care intervention, or to no intervention.”

After providing a detailed regulatory review and analysis, Kracov discussed several important practices, such as distinguishing FDAMA Section 114 information from:

• Off-label communications;
  
• Responses to Unsolicited Requests
  
• Good Reprint Practices Guidance; and
  
• CME
  

Kracov finally discussed the potential for kickback concerns and health care economic information. He explained that healthcare reform has created federal and state programs that can provide financial incentives, or exemptions from financial penalties (pay for performance (“P4P”) or shared savings programs) – e.g., ACOs.

If providers can use manufacturer health care economic information to achieve certain P4P program quality metrics, is there remuneration? Each P4P program includes a variety of quality measures and most quality measures could not be achieved solely through manufacturer-provided materials.

Since health care economic materials could offer only limited support to providers in satisfying measures required to achieve P4P program measures, arguably there is no remuneration? Since materials would advance the goals of P4P program, there is arguably a low risk of any fraud and abuse?