The United States Food and Drug Administration (“FDA”) released four new draft guidances on October 2, 2017 that aim to reduce the barriers for certain generic drugs to enter the market and ultimately, reduce drug prices. Reducing drug prices was a stated objective of President Trump during his campaign and has also been a topic that FDA Commissioner, Dr. Scott Gottlieb, has discussed. Dr. Gottlieb is not currently targeting direct regulation of brand-named drug prices; instead, he appears to be achieving his objective by increasing competition in the market by facilitating an increase in generic drug availability.
FDA released two draft guidances that focus on complex generics, which are generics that either have complicated ingredients or require use of unique delivery devices, and are hard to manufacture.
The first of these two draft guidances focusing on complex generics, ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin, focused on peptide drug products, which lack competition in the drug market, even though they do not possess market exclusivity. Specifically, the draft guidance provides advice to prospective applicants to determine when an abbreviated new drug application (“ANDA”) can be submitted for the following five peptide drug products: glucagon, liraglutide, nesiritide, teriparatide, and teduglutide. FDA hopes that ANDAs will allow for more generic products to enter the market, compared to the longer and traditional New Drug Application process. The FDA believes that technology now makes it possible for an ANDA applicant to show that the active ingredient in its generic synthetic peptide drug product is the “same” as the active ingredient in an already approved peptide of rDNA origin to qualify for an ANDA approval. The main takeaway of the draft guidance is the standard provided by the FDA for what it is generally looking for in an ANDA for a proposed generic synthetic peptide for which the reference listed drug (“RLD”) is a peptide of rDNA origin. Overall, the FDA is looking for the following factors, among other things, in the ANDA submission: 1) for each peptide-related impurity that is found in both the proposed product and the RLD, the level of such impurity in the proposed product is the same as or lower than that found in the RLD; 2) the proposed product does not contain any new specified peptide-related impurity that is more than 0.5 percent of the drug substance; 3) characterization of each new specified peptide-related impurity; and 4) justification for each new specified peptide-related impurity that is no more than 0.5 percent of the drug substance as to why such impurity does not affect the safety and effectiveness of the proposed product.
The second draft guidance on complex generics, Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA, discusses opportunities for meetings between FDA and a prospective ANDA applicant for a complex drug product. The draft guidance is part of the FDA’s efforts and missions under the recent reauthorization of the Generic Drug User Fee Amendments (“GDUFA II”). The draft guidance provides details about different types of meetings that can be requested with the FDA, such as product development meetings, pre-submission meetings, and mid-review-cycle meetings. The draft guidance also provides details about specific parts of the meeting request and meeting process, such as meeting request submissions, content to include in a meeting request, denials of meeting requests, presentations during meetings, and disputes over meeting minutes. FDA has provided the draft guidance in an effort to have more open communication between FDA and industry, which FDA hopes will lead to more complex drug products entering the drug market.
The other two draft guidances provide advice to industry on submitting and revising approval applications to the FDA that would assist generic drug manufacturers in bringing their products to market. One draft guidance, ANDA Submissions –Refuse-to-Receive Standards: Questions and Answers, provides FDA’s responses to questions submitted by industry about ANDAs and in reference to earlier guidance, ANDA Submissions—Refuse-to-Receive Standards. Generally, the questions and answers addressed topics such as the organization of an ANDA, review of and deficiencies associated with Drug Master Files, FDA filing decisions, product quality and bioequivalence reviews, and why the FDA may refuse to receive (“RTR”) an ANDA. An RTR decision by the FDA means that FDA has found that the ANDA is not substantially complete on its face to permit substantive review of the application by the FDA. The draft guidance highlights that ANDA applicants have the opportunity to correct deficiencies identified by the FDA during filing review. Specifically, FDA may allow applicants to correct minor deficiencies within seven calendar days and if this is done, the applicant will retain the original submission date. If the deficiency is major, the FDA will issue an RTR determination, and even if the ANDA is resubmitted, it would not keep the original submission date. The clarifications provided by the FDA aim to assist more drug makers in bringing their products to the market.
The last draft guidance, ANDA Submissions — Amendments to Abbreviated New Drug Applications Under GDUFA, explains how GDUFA II affects amendments to ANDAs and prior approval supplements (“PAS”) and details the different types of amendments. The draft guidance states that FDA considers each and every submission to an application to be an amendment. Further, the draft guidance explains how FDA will review these amendments and the effect of amendment submissions to an application’s review timeline. The draft guidance states that it supersedes the July 2014 draft guidance, ANDA Submissions – Amendments and Easily Correctable Deficiencies Under GDUFA. The draft guidance explains that GDUFA II simplified the amendment review process and amendments are no longer subjected to GDUFA I’s complicated tiered classification system. FDA review of the amendments under GDUFA II is still dependent on several factors though, and the draft guidance highlights that generally, the amendments will be designated as either standard or priority, categorized as major or minor, and receive a goal date based on certain factors, such as whether a preapproval inspection is needed.
FDA Commissioner Gottlieb also released a statement about the guidances and how they will assist with increasing access for patients to necessary drugs and overall improve public health. As a physician, a former cancer patient, and now head of the FDA, Commissioner Gottlieb has shown that he is committed to improving patients’ access to affordable drugs. Due to the recent resignation of former U.S. Department of Health and Human Services Secretary Tom Price, Commissioner Gottlieb has been considered a frontrunner to fill the position. The Health Law Pulse will continue to monitor FDA developments for generic drug products, drug pricing, and other key changes within the agencies.