FDA Announces Policy Initiatives to Facilitate Entry of Complex Generic Drugs

By Patricia Van Arnum - DCAT Editorial Director

February 1, 2019

The US Food and Drug Administration (FDA) Commissioner Scott Gottlieb said that the agency plans to advance policies, including the issuance of guidances, to promote drug competition and patient access for complex generic drugs. These are drugs that, by the nature of their formulation, delivery systems, or the complexity of their active ingredients, are harder to “genericize” under traditional approaches and a result, often face less competition. The move is consistent with the agency’s Drug Competition Action Plan, which was announced in 2017, to increase competition in the market for prescription drugs and facilitate entry of lower-cost alternatives.

“In 2019, we’ll advance additional policies to promote generic competition for complex drugs,” said Gottlieb in a January 30, 2019 statement. “Among other steps, we intend to issue additional guidance documents for developing specific complex generic drugs, as well as 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 As part of this, we intend to issue draft guidance with recommendations on establishing active ingredient sameness. In addition, we’re going to help advance the development of new analytical tools and in vitro tests that may provide additional accurate, sensitive and reproducible tools to support approval of complex generic drugs. Better tools can reduce complex generic drug development time and cost and can inform regulatory decisions.”

Gottlieb explained that there are a number of complex drugs that are no longer protected by patents or exclusivities but that continue to face no generic competition due to the difficulty of developing them. He explained more simple small molecules that are generics use more straightforward and reproducible manufacturing processes and are easy to characterize and evaluate through traditional methods, including human bioequivalence studies. For example, in many cases, a drug’s activity can be correlated directly with how quickly it got into the bloodstream and how long the drug stayed in the body, so it could have its intended effect on the anticipated site of action.

In contrast, he pointed out that complex drugs involve cases where the drug is often harder to develop 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, for example, inhaled drugs that act directly on the lungs, a topical patch that is activated directly on the skin, or eye drops that act on the surface of the eyes. The therapeutic effect of these types of drugs does not necessarily correlate directly to the amount of drug in the blood or it can be difficult to measure through the blood. “They can raise other issues that make the traditional, metrics generally used to develop generic drugs harder to employ. In other words, it can be more difficult to meet the standards for generic approval,” he said in the agency statement.

”These new policy efforts are aimed at ensuring that we provide as much scientific and regulatory clarity as possible with respect to complex generic drugs,” added Gottlieb. “This focus is critical because, first and foremost, these drug products provide important therapies to patients. We believe that they’re also becoming increasingly important to the economic stability of the generic drug industry. Being able to 'genericize' a complex medicine can be a high-value opportunity for a generic drug developer."

Source: US Food and Drug Administration