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Back to the forum  2018-06-25 17:17 CEST (UTC+2h)

CFDA: Draft guidance? [RSABE / ABEL]

posted by Helmut Homepage - Vienna, Austria, 2018-06-12 14:54  - Posting: # 18889
Views: 424

Hi libaiyi,

» CFDA has relased the draft guidance for HVBE, which follows FDA method (RSABE).


There is nothing like “highly variable bioequivalence”. Either the drug itself is highly variable (if the clearance is HV already seen after an iv dose or after an oral solution the absorption is HV: HVD) or a drug product is HV: HVDP. Since it not always known whether the drug itself is HV, when talking about formulations people like me leave the question open and prefer the term HVD(P).
Example diclofenac: iv and a solution show pretty low CVs (<15%). Hence, it is not an HVD. Suspensions, IR, and rectal products are not HVDPs (CVs 20–25%). On the other hand, gastric resistant formulations are borderline HVDPs (CVs 30–40%). Topical products are definitely HVDPs (crazy CVs).


I see. Is this link correct? Interesting the two attachments (#1, #2).
When it comes to replicate designs only the lousy partial replicate (TRR|RTR|RRT) and one full replicate (TRTR|RTRT) given in Tables 2&3. Never heard about the 3-period full replicate (TRT|RTR) and another 4-period full replicate (TTRR|RRTT)? Although not given in the tables, 4-sequence 4-period full replicates are also mentioned (TRTR|RTRT|TRRT|RTTR or TRRT|RTTR|TTRR|RRTT). Forget it; confounded effects.
From #2 it is clear that the FDA’s RSABE was 1:1 copied.

» I still have a question about EMA method. Do you mean if we follow EMA's guidance, the ABEL should be used rather than RSABE, …


» … please give me more advise.

As I wrote previously, SAS-code is given in the EMA’s Q&A-document. The EMA prefers a fixed effects model (‘Method A’).

Helmut Schütz

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