Bioequivalence and Bioavailability Forum • FDA: Update of PSGs to align with ICH M13A

Helmut
★★★

Vienna, Austria,
2024-10-03 17:58
(218 d 06:28 ago)

Posting: # 24213
Views: 2,382

FDA: Update of PSGs to align with ICH M13A [Regulatives / Guidelines]

Dear all,

the FDA published a list¹ of 826 Product-Specific Guidances which are planned to be updated in October 2024:

Planned Revised PSGs for Complex and Non-Complex Generic Drug
Products to Align with ICH M13A
In addition to removing the BE recommendations for BE studies under either fasting
or fed conditions as indicated in the table, these PSGs may also include editorial
revisions to language and formatting as deemed appropriate by the Agency.

For 118 products (14.3%) the recommendation of performing the studies in fasting condition will be removed. For 708 products (85.7%) the recommendation of performing the studies in fed condition will be removed. For the latter there are two products (pimavanserin tartrate, tablet and capsule), where a BCS-based biowaiver will be added as an option.

The current PSGs state ‘Bioequivalence based on 90% CI’ but not which PK metrics have to be assessed. According to the overarching guidance² C_max, AUC_0–t (or AUC_0–72 if t_½ > 24 h), and AUC_0–∞ but according to ICH M13A AUC_0–∞ is not recommended – and for a reason.
Will the FDA’s guidance be updated as well or will we still have to deal with the superfluous AUC_0–∞?

FDA. Upcoming Product-Specific Guidances for Generic Drug Product Development. Silver Spring, MD. 09/13/2024. Online.
FDA (CDER). Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA. Draft Guidance for Industry. Silver Spring, MD. August 2012. Download.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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Helmut
★★★

Vienna, Austria,
2024-11-01 09:58
(189 d 13:28 ago)

@ Helmut
Posting: # 24253
Views: 1,621

FDA: ICH M13A, Q&A, PSGs, and a rant

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Dear all,

on October 30^th the FDA published its final version of ICH M13A and the respective Q&A document. Trivial changes: Instead of decimal numbering of headings the FDA’s system (I–IV.A–D.1–8.a–e.).

Contrary to the previous announcement only 814 PSGs have been updated. See the full list; unfortunately without links to the PSGs.

There was demanding consensus-building process in the ICH’s M13 Experts Working Group (EWG) for more than five years. The result was:

If a drug product is intended for use in both sexes, the inclusion of male and female subjects in the study should be considered.

THX a lot, that was a step forward from the draft!

However, the FDA didn’t give a shit (excuse my French), ignored that and recommends in updated PSGs still inclusion of both sexes.

[image]

Sure, PSGs always overrule a general guidance but the FDA’s attitude is not what I consider \(\small{\color{Red}{\textsf{harmoni}}}\color{Red}{\frac{\textsf{s}}{\textsf{z}}}\small{\color{Red}{\textsf{ation}}}\).
Somehow it’s an insult to people working for and attending the GBHI-conferences and the non- [image]

members of the ICH’s M13 EWG.

If you didn’t endure the FDA’s 21 Nov 2024 Webinar: Slides
For brave ones: [image]

Recording

As usual I asked two questions:

The recommendation of including both sexes in the PSGs is driven by gender politics rather than science. Why were five years of consensus building in the M13 Expert Working Group ignored?
M13A recommends C_max and AUC_0-t only. The ANDA guidance requires also AUC_0-inf. Will the IR part of the ANDA guidance be updated accordingly in 2025?

Also as usual my questions were disregared.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes