As part of its Drug Competition Action Plan, the US Food and Drug Administration (FDA) has issued draft guidance to outline a new regulatory pathway for “competitive generic therapies” (CGTs) to provide certain incentives for industry to develop generics for drugs lacking competition. DCAT Value Chain Insights examines the program and how it fits into other initiatives by the FDA to improve generic-drug development and FDA’s review process.

Inside FDA’s new regulatory pathway for competitive generic therapies

“The FDA is taking another step to encourage generic entry for drugs that face inadequate competition by laying out new, efficient guidelines for the use of a novel pathway that provides incentives for developing generic versions of drugs that currently face little or no competition,” said FDA Commissioner Scott Gottlieb in a February 15, 2019 statement. “…This new guidance provides robust information on how drug developers can apply for CGT designation and when they may be eligible for CGT exclusivity. The CGT pathway is intended to incentivize effective development, efficient review, and importantly the timely market entry of generic drugs.”

Under the draft guidance, designation of a drug as a CGT can be granted to a company submitting an application for its generic drug when there’s inadequate generic competition for that drug, meaning there is not more than one approved drug in the active section of the Orange Book, officially known as the Approved Drug Products with Therapeutic Equivalence Evaluations Publication, which provides a list of drug products approved by the FDA under the Federal Food, Drug, and Cosmetic Act that includes patent and exclusivity information and identifies whether a drug is currently being marketed or has been discontinued. The designation as CGT was established by Congress when it granted the FDA new authorities in the FDA Reauthorization Act of 2017 and provides certain incentives for industry to develop generics for drugs lacking competition that have been designated as CGTs.

Under this pathway, companies may submit requests to designate a drug as a CGT at the time of submitting an abbreviated new drug application (ANDA) or at any time before the original ANDA submission. At the request of the applicant, the FDA may expedite the development and review of an ANDA for a drug that is designated as a CGT. The FDA says that a CGT designation can afford companies a number of early benefits, including product-development meetings with the FDA to discuss specific scientific issues or questions they may have such as proposed study design or alternative approaches. The FDA says that these early benefits may also help to reduce the number of application review cycles, thereby decreasing the time it takes for the generic drug to receive approval. If a CGT designation is granted, the application may be eligible for a 180-day period of marketing exclusivity provided the applicant is the first approved ANDA for that CGT and meets other conditions.

To date (as of February 15, 2019), the FDA has granted more than 100 CGT designation requests, and in 2018 between August and December, the FDA approved the first five ANDAs for generic drugs designated as CGTs, according to information from the FDA. When the drugs covered by those ANDAs were commercially marketed, those ANDAs qualified for 180-day exclusivity.

Other initiatives by the FDA to improve generic-drug development and review

The FDA’s implementation of a CGT pathway is part of the agency’s Drug Competition Action Plan, which was announced in 2017 as a means to foster generic-drug competition and “help address the high cost of drugs and improve patient access to important medicines,” said Gottlieb in his statement.

Gottlieb outlined the measures the agency has taken thus far and plans to take as part of those goals. ”We’ve been taking new policy steps at the FDA to support downward pressure on drug prices by helping to clear a path for more efficient generic development,” Gottlieb said in the statement. “In doing so, we know that various factors may influence a manufacturer’s decision to develop and market a generic drug. For example, some drugs may not attract a high level of interest if there is a limited market for them. We also know that some drugs may be less desirable to genericize because they are complex drugs, which are more difficult to copy. We’re working to reduce barriers to generic development and to lower the cost of generic entry so that more of the generic medicines that the FDA approves are launched and reach patients. Over the next year, the FDA will advance additional policies to promote generic competition including for complex drugs,” he said in the statement.

Gottlieb said that among other steps that the agency plans to take is to issue additional guidance documents for developing specific complex generic medicines as well as to address categories of complex drugs that are hard to copy because of their complex formulation or mode of delivery. This will include the publication of a series of guidances to address regulatory and scientific challenges that make it generally more difficult to develop complex generics. As part of this, he said that the agency intends to issue draft guidance with recommendations on establishing active ingredient sameness. In addition, he said that the agency will advance the development of new analytical tools and in vitro tests to provide additional accurate, sensitive and reproducible tools to support approval of complex generic drugs. Better tools for proving sameness can open up more complex drugs to generic competition.

In addition to taking action to enhance generic competition, the FDA said it is working to make generic drug development more efficient and predictable. “We’re working to reduce approval times and to enhance the efficiency of certain aspects of the submission process for generic drug applicants,” he said. “And we’re also working to provide the generic industry with increased transparency to provide greater certainty around timing of first possible generic entry and potential competition from other generic entrants, and to make the scale-up of manufacturing more efficient, to enable more informed decisions on how to prioritize their resources and come to market. We also recently announced a guidance providing application holders with clarity on information they are required to share with the FDA under another FDARA [The FDA Reauthorization Act of 2017] provision that will enable us to have more timely, accurate information about what drugs are being actively marketed to help provide transparency around circumstances where generic competition is lacking to inform our policy making.”