Maryland : The US Food and Drug Administration (FDA) this week issued 36 new and revised draft product-specific guidances meant to facilitate the development of generic drugs by clarifying the agency’s expectations for the studies required to demonstrate bioequivalence (BE) to a reference listed drug (RLD).
The latest batch of guidances includes 22 new and 14 revised draft guidances covering drugs to treat prostate cancer, hepatitis C, multiple sclerosis and numerous other conditions.
With the new release, FDA says it has published 1,885 product-specific guidances. With the previous batch of product-specific guidances last November the agency had reported the total to be 1,974, which it says was due to an error that caused some of the guidances to be counted twice. (RELATED: FDA issues 34 new and revised product-specific guidances, Regulatory Focus 18 November 2020).
“The PSG database was recently updated to fix an issue that caused some of the PSGs to be counted twice, leading to an incorrect higher number. This error was fixed between November 2020 and March 2021. The current number displayed on our website correctly reflects the number of PSGs published to date,” an FDA spokesperson told Focus.
Of the 36 new or revised guidances, FDA says that 30 are for drugs with no approved generics, including eight complex products. The recommendations in five of the new and revised guidances for complex products were developed based on research conducted by FDA’s Generic Drug User Fee Amendments (GDUFA) science and research program.
Among the revised draft guidances are PSGs for generic versions of two metered dose inhalers, Alvesco (ciclesonide inhalation aerosol) and Atrovent HFA (ipratropium bromide inhalation aerosol) that recommend using a weight-of-evidence approach to demonstrating bioequivalence that includes in vitro BE studies, pharmacokinetic BE studies and comparative clinical endpoint BE studies.
The revisions to the two guidances now offer an alternative to conducting comparative clinical endpoint BE studies involving in vitro, in vivo and in silico studies. “With the revisions to these two PSGs, FDA aims to facilitate greater access to affordable generics by providing the generic industry with the Agency’s current scientific thinking for establishing BE for generics referencing Alvesco and Atrovent HFA, neither of which has an approved generic,” FDA says.
In addition to issuing the new and revised documents, FDA has updated its list of upcoming product-specific guidances.
FDA has also recently withdrawn two product-specific guidances for generic versions of Belviq (lorcaserin hydrochloride) and Belviq HQ (lorcaserin hydrochloride) after determining that the products were withdrawn from sale for safety or effectiveness reasons. In February 2020, Eisai voluntarily withdrew the two drugs from sale at FDA’s request after a large postmarketing study found increased rates of certain cancers among patients taking the drugs. (RELATED: Eisai voluntarily withdraws Belviq at FDA’s request, Regulatory Focus 13 February 2020).
FDA says it has withdrawn the corresponding product specific guidances for lorcaserin hydrochloride as it will no longer accept or approve abbreviated new drug applications (ANDAs) for the drug.