US FDA issues guidelines to help generic makers to copy 32 complex drug products


The US drug regulator, in its efforts to bring competition and reduce development hurdles for complex generic drugs, has released new draft guidelines for 32 drugs. The guidance covered a range of drugs that included Mylan’s auto-injector EpiPen (epinephrine) to treat allergic reactions, GSK’s aerosol metered dose inhaler (MDI) Serevent to treat asthma, Novartis’ cancer treatment Afinitor and AstraZeneca’s cancer treatment Lynparza, among others.

In addition to draft guidelines, the US FDA released 19 revised guidance documents, including the one for companies looking to develop generics of Eli Lilly’s erectile dysfunction drug Cialis and other antibiotics, antiviral and ophthalmic drugs.

A complex drug often involves a complex active ingredient, or sites of action; complex drug products also include complex drug-device combination products such as metered dose inhalers used in treatment asthma and auto-injectors. These medicines generally have at least one feature that makes them harder to copy under traditional approaches. As a consequence, despite expiration of patents these drugs face less competition, and are priced expensively.

US FDA has been trying to encourage competition in complex drugs through several initiatives. One of the major steps is to issue new draft and revised guidance documents to provide product-specific clarity enabling generic makers to design appropriate bio-equivalence (BE) studies in support of their abbreviated new drug applications (ANDAs) filings.

“The guidance provides information on requesting and conducting product development meetings, pre-submission meetings, and mid-review cycle meetings with (US) FDA. These meetings will allow for enhanced communication between generic drug applicants and (US) FDA early in the generic drug development process, allowing for more efficient generic drug development, review, and approval pathways,” said Scott Gottlieb, US FDA Commissioner said earlier this month on US FDA blog articulating the agency’s plan of action to bring more generic competition for complex drugs.

The latest guidelines will help Indian drug makers who are struggling to develop and getting approvals for complex generic drugs, especially in the areas of metered dose inhalers.

Makers of complex generic drugs face difficulties in developing and demonstrating that their products meet the approval requirements for generic drug applications, including establishing that they are bioequivalent to and have the same active ingredient as the brand-name drug.

“Bioequivalence for complex generic drugs can be challenging with complex drug products that can’t be easily measured in the blood, or when the drug’s therapeutic effect is delivered locally to a particular organ, rather than systemically, through the bloodstream. In other instances, showing active ingredient sameness can be challenging when the drug product contains an active mixture of components and not a single active molecule,” Gottlieb said.

“These challenges – and resulting regulatory uncertainties – may deter generic manufacturers from beginning development. It can mean these ANDAs undergo more review cycles than other generic drugs. These hurdles, in turn, may result in limited competition and higher prices.” Gottlieb added.