Drugmakers and industry groups are calling for changes to the US Food and Drug Administration’s (FDA) draft guidance on bioavailability (BA) studies submitted as part of an investigational new drug (IND) application or new drug application (NDA).
The 27-page draft guidance was released
for comment in February and when finalized will replace the agency’s 2014 draft guidance Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs – General Considerations
While the comments from drugmakers are largely supportive of the draft guidance, among them are calls for specific changes and additional clarity from FDA.
In its comments, industry group PhRMA says it supports the draft guidance, but recommends some changes relating to pharmacokinetic (PK) and pharmacodynamic (PD) modeling, PD studies and bioanalytical methodology. PhRMA also suggests the agency add sections or discussion of several topics, including BA/bioequivalence (BE) waivers; FDA’s recent draft guidance on food effect studies; and batch sizes for pivotal BE studies.
Both Merck and Pfizer join PhRMA in requesting that FDA explain either in the Federal Register
notice accompanying the final guidance, or in the final guidance itself, why the agency is replacing the 2014 draft guidance.
Pfizer and PhRMA also question why FDA removed bioequivalence from the title of the guidance, when bioequivalence studies are still referenced in the document.
“This guidance focuses on BA studies, whereas the guidance it will replace covered both BA and BE studies. It is not clear if there will be another guidance to address BE studies,” Pfizer writes, while AstraZeneca requests that FDA replace mentions of BE with BA.
“If demonstration of BE is not a requirement, we suggest replacing ‘BE studies’ with ‘BA studies’ in this guidance,” AstraZeneca says.
PhRMA, along with AstraZeneca, Janssen, Pfizer and the International Consortium for Innovation and Quality in Pharmaceutical Development, argue that FDA should include a discussion of PKPD or physiologically-based pharmacokinetic (PBPK) modeling.
“The lack of any discussion on the use of PBPK modeling or other in silico
approaches to evaluating BE seems to be a significant omission,” Pfizer writes.
PhRMA also asks FDA to add recommendations to the final guidance discussing bioavailability determinations for drug-device combinations when a new device is used with an existing drug formulation.
“In particular, guidance is needed on the circumstances under which an in vivo
study is recommended, versus when the drug and device combination can be approved based on comparability results from in vitro
studies assessing the performance of the device,” PhRMA writes.