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FDA kicks off new efforts to advance complex generics

FDA commissioner Scott Gottlieb on Tuesday announced a series of guidance documents that will advance the development of generic transdermal and topical delivery systems.

“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,” Gottlieb said, in a statement.

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"The new guidances we’re releasing include the revised draft guidance, Assessing Adhesion with Transdermal and Topical Delivery Systems for ANDAs, which provides updated advice for the design and conduct of studies evaluating the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 A second draft guidance, Assessing the Irritation and Sensitization Potential of Transdermal and Topical Delivery Systems for ANDAs, provides recommendations for the design and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," Gottlieb said.

In addition to these documents, the FDA also is 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," Gottlieb said.

Gottlieb said that 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.

In the coming months, the FDA said it would 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 complex drugs. More efficient tools for demonstrating sameness can reduce product development time and cost and inform regulatory decisions, Gottlieb said.

The FDA also will 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.

Gottlieb said the agency also will be clarifying the agency's policies on how it evaluates 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.
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