FDA revises more than 800 PSGs in line with ICH M13A

The US Food and Drug Administration (FDA) on Thursday published revised draft product-specific guidances (PSGs) for immediate-release solid oral generic drugs deemed to be low risk that will no longer require two bioequivalence (BE) studies – one fed and one fasting – to demonstrate BE to a reference-listed drug. Instead, sponsors can choose to conduct either a fed or fasting bioequivalence study for the affected drugs.

The action aligns with the International Council for Harmonisation’s (ICH) M13A guideline, which was adopted in August 2024 and issued as final guidance by FDA this week. (RELATED: ICH adopts M13A guideline on bioequivalence testing, Regulatory Focus 6 August 2024)

FDA said in a notice accompanying the guidance that the document “aims to increase the efficiency of drug development and accelerate the availability of safe and effective orally administered immediate-release solid oral dosage forms.” FDA is issuing the PSGs that have been affected by ICH M14 in batches.

FDA is planning to revise another 44 PSGs affected by ICH M13A, according to its list of planned PSGs, bringing the total number total number of PSGs that have been affected to 814.

Speaking at a PQRI/EUFEPS meeting earlier this year, FDA’s Lei Zhang, rapporteur of the M13A Expert Working Group, said that adoption of the M13A guideline would impact a “large portion of the generic drug market” and that FDA would need to revise a majority of its product-specific guidance (PSGS) for IR solid oral dosage products. (RELATED: ICH M13A BE testing guideline expected to be adopted this summer, Regulatory Focus 17 April 2024)

In the notice, FDA announced that “these revised product-specific guidances recommend that ANDA applicants conduct one bioequivalence study for products with a non-high risk of bioequivalence due to food effect under either fasting or fed condition rather than conducting two bioequivalence studies: one BE study under fasting conditions, and one BE study under fed conditions.”

FDA also recommends that applicants consult with the general guidances on bioequivalence when designing and conducting BE studies for IR solid oral dosage forms.

Robert Pollock, a senior advisor with Lachman Consultants, wrote in a recent blog post that this move will help generic drug companies reduce their development costs yet will hurt contract research organizations (CROs) as “half of their business from BE studied for generics will be lost.” He noted that “this development begs the question as to whether CROs will begin raising their prices for the single studies to help make up the difference in lost revenue.”

He also wrote that the action prompts some “unanswered questions” such as whether companies can stop a fed study that is in progress if the requirement for the fed study has been eliminated.

Pollock told Focus that most, but not all, generic IR drugs are deemed low risk and that certain IR complex generics such as liposomal drugs, are in a higher risk category.

FDA will be holding a webinar on 21 November to discuss its implementation of the guidance. The webinar will outline the agency’s plans for implementing the guidance as well as clarify questions raised on the guidance.

The deadline for commenting on the notice is 30 December 2024.

Federal Register notice

FDA revises more than 800 PSGs in line with ICH M13A

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