Elemental Impurities Deadline Contributes to Spike in CRLs for Generic Drugmakers

New generic drug applications are not winning a lot of approvals from the US Food and Drug Administration (FDA) so far in January 2018, and at least part of the reason for an increase in complete response letters (CRLs) is a new requirement from the US Pharmacopeia (USP).

Lachman Consultants' Bob Pollock, a former official in FDA’s Office of Generic Drugs, first discussed the low number of abbreviated new drug application (ANDA) approvals in January – just four approvals through 16 January – that might be linked to a new USP requirement on documentation of elemental impurities, as outlined in a draft guidance document from June 2016: “Control of Elemental Impurities in Drug Products.” The draft offers guidance on two USP chapters, USP<232> Elemental Impurities - Limits and USP<233> Elemental Impurities – Procedures and ICH Q3D Elemental Impurities.

FDA told Focus in a statement: “The January date is the end of a lengthy implementation period that was designed to give manufacturers ample time to meet the requirements. Applications that do not meet these requirements are unable to be approved and may receive a request for this information through an information request or complete response letter.”

But USP said that companies receiving CRLs for not meeting the new requirements knew they were coming for almost a decade and the implementation date of 1 January 2018 was first announced in 2015.

The Rockville, MD-based USP also explained to Focus in a statement: “The chapters establish a new approach for limiting elemental contamination in drug products. This approach replaces the 100 years old heavy metal test.”

Though USP also said that it does not think that meeting the requirements are the cause of the uptick in CRLs, USP added: “The transition to the new paradigm requires work up front. Pharmaceutical manufacturers need to assess the contribution of elemental impurities from all possible sources including raw materials, manufacturing process, packaging systems, etc. This assessment should have started a long time ago thus it is very unlikely that this could be the cause of a slower pace for ANDA approvals.

“FDA has been requiring new drug products to meet these new requirements since June 2016,” USP added.