1250 Broadway, 27th Floor New York, NY 10001


Statement from FDA Commissioner Scott Gottlieb, M.D., on new efforts to advance the development of generic copies of complex drugs to improve patient access to medicines

As part of the U.S. Food and Drug Administration’s efforts to promote drug competition and patient access, we’ve advanced many policies aimed at making it more efficient to bring generic competition to the market. We have been especially focused on a category of medicines known as complex drugs. These are drugs that, by nature of their formulation or delivery systems for example, are harder to “genericize” under our traditional approaches. As a result, these drugs often face less competition.

Today, we’re announcing a series of guidance documents that will advance the development of generic transdermal and topical delivery systems (TDS). The increased transparency and predictability provided by these and other product-specific recommendations gives applicants seeking to develop generic copies of these complex products a better opportunity to efficiently advance these products and prepare better and more complete submissions.

TDS products are applied to a patient’s skin and deliver the drug into and through the skin. These products should deliver the correct medication dose consistently and for the expected length of time. They should adhere consistently and uniformly to the skin, and should withstand variables such as exposure to water, humidity and movement. Because of the inherent complexity of delivering a drug through a TDS, making generic copies of these complex drugs can be especially hard. As a result, many branded TDS products like drug patches have not faced timely generic competition.

The new guidances we’re releasing include the revised draft guidance, Assessing Adhesion with Transdermal and Topical Delivery Systems for ANDAs, which provides updated advice for the design and conduct of studies evaluating the adhesive performance of a proposed generic TDS. A second draft guidance, Assessing the Irritation and Sensitization Potential of Transdermal and Topical Delivery Systems for ANDAs, provides recommendations for the design and conduct of studies to evaluate the in vivo skin irritation and sensitization potential of a proposed generic TDS.

In addition to these documents, the FDA is also issuing 25 product-specific guidance documents. These include two new and 23 revised guidances. These documents will support industry in identifying appropriate science-based methodologies and evidence for developing generic TDS products.

In too many cases, there is no generic competition for these costly branded drugs even after they have lost their exclusivity protections. We have made a new commitment to develop product specific guidance documents laying out how to develop a generic copy of a branded medicine for any currently marketed, branded complex medicine in an effort to advance a more efficient and effective framework for developing generic copies of complex drugs. We will strive to release each document as soon as scientific recommendations can be developed.

To understand the challenges posed by complex generics, 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 requiring simple manufacturing processes. They were generally easy to characterize and evaluate through traditional methods, including traditional 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 involve cases where the drug is often harder to formulate and manufacture because it has a complex formulation or complex active ingredient. In other cases, the drug acts locally on the tissue rather than through the concentration in the blood. This includes inhaled drugs that act directly on the lungs, a topical patch that acts directly on the skin, or an eye drop that acts on the surface of the eye. The therapeutic effect of these types of drugs does not necessarily correlate with the amount in the blood and can be more difficult to measure through the blood. They can raise other issues that make the traditional, and often simpler, metrics generally used to evaluate generic drugs and prove sameness difficult to employ. There’s often no easy way to make the demonstrations necessary for generic approval.

These draft guidances are aimed at ensuring that we provide as much scientific and regulatory clarity as possible with respect to complex generic drugs. This focus is critical because, first and foremost, these drug products provide important therapies to patients. We believe they’re also becoming increasingly significant to the economic health of the generic drug industry. Being able to “genericize” a complex drug can be a high-value opportunity for a generic drug developer. These higher value generic business opportunities can help underwrite the costs of other generic applications at a time when we believe the generic industry is facing new economic pressures from rising costs, supply chain consolidation, increased competition and declining reimbursement on many competitive generic medicines. Moreover, because brand-name versions of complex drug products are often higher-priced than many other brand name drugs, any steps we can take to encourage the development of generic competitors for complex drugs may have an outsized impact on access and drug spending.

In the coming months, we’re going to advance other new policies to promote more generic competition for these complex drugs. This includes the development of new analytical tools and in vitro tests that may be more accurate and sensitive, and reproducible tools to demonstrating sameness between a generic and branded version of a complex drugs. More efficient tools for demonstrating sameness can reduce product development time and cost and inform regulatory decisions.

We’ll also be issuing an umbrella guidance to help generic drug developers address some of the most challenging regulatory and scientific issues encountered when they try to make generic copies of complex drugs. This umbrella guidance will be followed by a series of more targeted guidances to help address legal questions that may be blocking generic competition.

We’ll also be clarifying our policies on how we evaluate potential differences in instructions for using complex generic drugs, for example when there are directions for how to use a specific drug delivery device in an approved drug-device combination.

Addressing these challenges – and promoting more generic competition to complex medicines – is a key part of our Drug Competition Action Plan, and our efforts to promote patient access and more affordable medicines.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by 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.