On July 18, 2017, FDA held a public meeting to address efforts to ensure a balance between innovation in drug development and accelerating the access of the public to lower-cost alternatives to innovator drug therapies is maintained under the Drug Price Competition and Patent Term Restoration Act (known as the Hatch-Waxman Amendments). Through the public meeting and docket, FDA is seeking comments on how elements of the approval process for innovator and generic drugs, including exclusivities and other provisions created by the Hatch-Waxman Amendments or other FDA regulatory provisions, have been used in ways that “inappropriately” hinder generic competition. In addition, FDA wanted to better understand how external factors to FDA regulation, such as patent litigation, commercial decisions to market, and restrictions on availability of innovator drug samples, can be addressed to improve the development or marketing of generic or follow-on applications.
FDA Commissioner Is Seeking Ways the FDA Can Facilitate “Increased Competition”
In his opening remarks at the public meeting, FDA Commissioner Scott Gottlieb, M.D. explained that drug pricing is a complex confluence of factors, including scientific and regulatory risk, time required to develop drugs, and the cost of drugs that ultimately do not make it to market. As such, he stated that FDA was looking at ways to reduce the time required for, and uncertainty of, drug development.
At the same time, Dr. Gottleib expressed concern that some innovator drug companies have been “gaming the [drug approval] system” to deliberately slow down the public availability of lower cost generic or follow-on drug alternatives. He stated that key components of the Drug Competition Action Plan include looking for places where this sort of gaming is happening, and changing FDA rules where it can.
Dr. Gottlieb also stated that FDA was looking at how it could address scientific and regulatory obstacles to abbreviated new drug application approval. For example, FDA plans to:
- Issue a new Manual of Policy and Procedures regarding how FDA receives ANDAs and an industry guidance for good ANDA submission practice to avoid common deficiencies and multiple review cycles;
- Consider making public applicant requests for samples in order to better expose availability issues;
- Ensure that FDA’s own regulatory practices are in line with science by providing enhanced communication and meetings for complex drugs; and
- Continue to develop efficiencies in the review process, such as by making complete response letters more clear and understandable to help reduce the need for multiple review cycles.
Janet Woodcock, M.D., Director of the Center for Drug Evaluation and Research, noted in her opening remarks that FDA was “one piece of the puzzle” in the general issue of competition between innovator and generic companies. While FDA is still trying to understand why some drug shortages happen or companies stop making some generic drugs, FDA believes it can help by identifying opportunities for generic drug development and approval. To that end, FDA recently published a list of off-patent, off-exclusivity drugs that do not currently have an approved ANDA, and FDA has prioritized review of ANDAs for those drugs.
Speakers Identify Broad Concerns Regarding FDA Regulations
After the opening remarks, a panel of representatives from the CDER’s Offices of New and Generic Drugs and Regulatory Policy, FDA’s Chief Counsel, and the Federal Trade Commission Bureau of Competition heard comments from a variety stakeholders in the pharmaceutical area, including both innovator and generic pharmaceutical companies, insurers, healthcare providers, legal academics, and public interest groups representing patients. These speakers outlined a broad set of concerns, some that are briefly outlined below.
Restricted Distribution and REMS
Several speakers expressed concern that restricted distribution programs, particularly those with Risk Evaluation and Mitigation Strategies (REMS) that include Elements to Assure Safe Use (ETASU), have been used to block access to innovator product samples for ANDA bioequivalence testing. In addition, some noted how statutory requirements for attempting to negotiate a single-shared REMS have slowed ANDA approvals and product marketing.
On the other hand, innovator industry representatives thought that FDA needed to provide more guidance for when ETASU REMS samples may be provided without raising liability concerns. Moreover, the innovator companies raised concerns about making many samples available, particularly for specialty products, such as some biologics with limited production cycles. Further, from their viewpoint, FDA, innovator companies, and generic companies had successfully developed shared REMS programs..
Many noted that Citizen Petitions—particularly those filed close in time to approval of a generic version of the innovator’s drug—can delay and frustrate generic entry, noting that virtually all such petitions have been denied. But innovator industry representatives believed that petitions were necessary, because manufacturers often have critical information regarding their own drug products that FDA needs to consider in this type of public forum before approving generic and follow-on products that otherwise may put the public at risk.
“Product Hopping” and “Evergreening”
Representatives from managed care organizations suggested that FDA should take steps to curtail innovator companies from “evergreening” or “product hopping”—e.g., reformulating an approved product in favor of a newer version with minor improvements ranging from longer release time to scores to help divide tablets, which they contended increase drug costs while not necessarily improving patient outcomes. Yet innovator companies argued that the market, including physicians and patients, should decide whether the improvements warranted additional cost over available generic versions of discontinued innovator products.
Improving the ANDA Review Process
Several representatives from generic companies requested that FDA look at additional ways to improve the efficiency of generic review process, in particular the way in which FDA may revise its bioequivalence guidance only after ANDA applicants have conducted studies under prior recommendations. Kathleen Uhl, M.D., Director of CDER’s Office of Generic Drugs, however, noted that these changes are required when FDA’s updates or improves its understanding of bioequivalence for a particular product, sometimes only after learns more about the product from the initial filed ANDAs. Other generic company representatives expressed concern about how FDA handles labeling changes initiated or required only months or days before ANDA approvals, especially when such labeling changes do not add critical safety or efficacy information and could be handled post approval. Above are just some of the points raised at the public meeting. FDA will continue to accept written comments until September 18, 2017. Any written comments should be submitted via regulations.gov to docket number FDA-2017-N-3615.