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FDA Statement

Statement from FDA Commissioner Scott Gottlieb, M.D. responding to report from GAO and updating on FDA’s ongoing efforts to increase access to complex generic drugs

For Immediate Release:
Statement From:

Today the U.S. Government Accountability Office (GAO) published a report titled “Generic Drugs: FDA Should Make Public Its Plans to Issue and Revise Guidance on Nonbiological Complex Drugs.” In preparing the report, GAO studied a number of issues related to the FDA’s review and approval of “nonbiological complex drugs.” The report contained a single recommendation for the FDA -- that the agency publicly announce its plans to issue or revise guidance for these drug products. We agree with GAO’s recommendation and the FDA is actively working to accomplish this goal through new policies that are already underway.

One of the first actions I took when I arrived at the FDA was announcing our Drug Competition Action Plan. This comprehensive plan was aimed at promoting competition and access, especially when it came to the development of generic drugs in pharmaceutical categories that lacked competition.

Since announcing our plan, we’ve advanced many policies aimed at making it easier to bring generic competition to a category of branded drugs known as complex drugs, which by nature are harder to “genericize” under our traditional approaches. As a consequence, these drugs can face less competition. We are currently undertaking an economic analysis to evaluate the impacts of our policies, and to guide further policymaking. We will release the results of this analysis as soon as it’s available.

So what is a complex generic drug? And why could it be harder to establish therapeutic equivalence to a complex drug in order to meet the FDA’s generic drug approval requirements?

Often, these are cases where the drug involves a complex formulation or complex active ingredient. In other cases, the drug acts locally on tissue, like an inhaled medicine that acts directly on the lung, or an eye drop that acts on the surface of the eye. In some cases, costly, branded drugs that are complex drugs have lost their exclusivity, but there is no generic competition.

To understand the issue, we need to go back to the pathway developed in 1984 under the Hatch-Waxman Amendments. This legislation put into place the framework for generic drug review, at a time when most drugs were simpler small molecules. They were generally easy to characterize and evaluate through bioequivalence studies. In most cases, a drug’s activity correlated directly with how quickly it got into the blood, and how long the drug stayed in the blood, so it could have its intended effect on the intended site of action.

In contrast, complex drugs are often harder to formulate, more difficult to measure through the blood, or raise other issues that make the traditional, and often simpler, metrics generally used to evaluate generic drugs difficult to employ. There’s often no easy way to make the demonstrations necessary for generic approval.

Although we don’t formally recognize “nonbiological complex drugs” described in today’s GAO report as a separate class of drug products, we do recognize that the category of “complex generics” -- the term that we typically use to describe this group of drug products -- presents certain challenging scientific and policy issues. These challenges warrant specialized consideration by the agency. That’s why we’re looking for ways to maximize scientific and regulatory clarity with respect to complex generics. 

The FDA has long-recognized the need to expend additional resources to support the development and approval of complex generics, including the regulatory science underlying these drug products. For example, to assist the generic drug industry with identifying the most appropriate methodology for developing drugs and generating evidence needed to support ANDA (Abbreviated New Drug Application) approval, the FDA publishes product-specific guidances describing the agency’s current thinking and expectations on how to develop generic drug products therapeutically equivalent to specific reference-listed drugs. To date, we have published 1,541 of these guidances with 130 in 2017 alone; 47 of those were specific to the development of complex generic drug products

To this end, and as part of the recent reauthorization of the Generic Drug User Fee Amendments in 2017 (GDUFA II), the FDA will focus resources specifically intended to aid generic drug developers of complex products. This includes our efforts as part of the pre-ANDA program, through which specialized advice can be provided on the generic drug development pathway. It also includes timely development of new product-specific guidance for complex generics. As part of GDUFA II, the FDA committed to issuing guidance for a complex product as soon as scientific recommendations are identified. 

Additional actions that the FDA is taking under the pre-ANDA program include regulatory science research that prioritizes new and more efficient methods to demonstrate equivalence of complex generics, and making available face-to-face meetings with industry to clarify regulatory expectations early in the development of complex generics.

In 2017, we issued four general guidance documents covering complex generics:

  1. Draft Guidance for Industry: ANDAs for Certain Highly Purified Synthetic Peptide Drug Products that Refer to Listed Drugs of rDNA Origin (October 2017);
  2. Draft Guidance for Industry: Formal Meetings between FDA and ANDA Applicants of Complex Products under GDUFA (October 2017);
  3. Draft Guidance for Industry: Determining Whether to Submit an ANDA or a 505(b)(2) Application (October 2017); and
  4. Guidance for Industry: General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products (November 2017).

Looking forward, we’re working to develop additional guidance for industry with the aim of clarifying “sameness” requirements for ANDAs. We believe that guidance in this area may be particularly helpful for complex generics; including specific guidance on drug-device combination products.

The specific request outlined in GAO’s current report is that the FDA publicly announce its plans to issue or revise such guidances for complex generics. The FDA is actively working to do just that.

We believe that increased transparency on product-specific requirements gives manufacturers seeking to develop generic copies of complex drugs a better opportunity to efficiently allocate resources. We note that the existing practice of issuing product-specific guidances was a response to these same issues. Prior to 2007, the agency provided guidance on how to design bioequivalence studies for specific products only when asked for assistance by individual applicants. We believe that the publication of 1,541 product-specific guidances since 2007 has been a valuable resource welcomed by the generic industry. We believe the incremental steps outlined by the GAO will also be beneficial.

Our aim is to make sure that our policies and regulations – and our scientific and clinical standards – keep pace with the nature of these complex products, as well as the challenges we face in protecting consumers and promoting drug competition and access when it comes to generic medicines. Greater access to high quality generic drugs is key to giving us more ways to advance the public health.

The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.



Sandy Walsh

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