FDA Seeks to Reduce Hurdles for Complex Generic Drug Development

Drug-device combos and some injectable drugs fall into this class

The FDA has announced what its commissioner called “a major new set of policies” aimed at making it easier to bring generic competition to a category of branded medications known as complex drugs.

Such products include high-cost medicines like metered-dose asthma inhalers and some injectable drugs, FDA Commissioner Scott Gottlieb, MD, wrote in a blog post on the FDA website. ”These medicines generally have at least one feature that makes them harder to ‘genericize’ under our traditional approaches. As a consequence, these drugs can face less competition,” he said. Some of these drugs have lost their exclusivity but still face no generic competition.

Gottlieb said the agency’s new policies “are aimed at ensuring that we provide as much scientific and regulatory clarity as possible with respect to complex generic drugs.” Not only are they important to patients, he said, but they’re also “increasingly significant to the economic health of the generic drug industry.”

Complex drugs include products where the active ingredient itself is complex, Gottlieb said, citing the example of glatiramer acetate injection, a drug used in the treatment of multiple sclerosis. But the category is much larger, extending, for instance, to complex drug-device combination products. “This complexity, in turn, means that the scientific and regulatory pathways for approval of generic versions of these drug products are not as well traveled by generic drug developers,” he added.

Regulatory requirements affect both the direct and indirect costs of drug development, he noted: the time it takes to develop a drug and gain regulatory approval as well as costs associated with the research and development of experimental products that ultimately do not make it to market.

So the agency is “taking a number of new steps to support the development of high quality ANDAs [abbreviated new drug applications] for complex generic drugs,” Gottlieb said:

  • The FDA is issuing a draft guidance to assist ANDA applicants and prospective ANDA applicants in creating and submitting pre-ANDA meeting requests so the FDA can give better advice to sponsors looking to develop complex generic drugs. Such meetings allow for enhanced communication between applicants and the agency early in the drug development process, allowing more efficient generic drug development, review, and approval pathways.
  • The FDA is issuing a draft guidance to help applicants determine when submission of ANDAs for certain complex products known as peptides would be appropriate. Peptides are compounds made up of 40 or fewer amino acids. A number of branded medicines are peptides for which exclusivity has lapsed, but these drugs face little or no competition. This new guidance applies to ANDAs for specific synthetic peptides—glucagon, liraglutide, nesiritide, teriparatide, and teduglutide—that are manufactured using recombinant DNA technology.
  • The FDA’s generic drug regulatory science program will work to develop more tools, methods, and efficient alternatives to clinical endpoint testing where feasible. Bioequivalence for complex generic drugs can be challenging to measure, and showing that active ingredients are the same can be difficult when the drug product contains an active mixture of components and not a single active molecule.

Source: FDA; October 2, 2017.