Population pharmacokinetics: Drugmakers seek clarity and additions to revised FDA guidance
About a dozen drugmakers and industry groups recently offered their opinions on a revised FDA draft guidance related to population pharmacokinetics (PK) analyses submitted as part of new drug applications and biologic license applications.
The comments largely seek specific tweaks to the 23-page revised draft, which was released in July, although some of the comments also seek further clarity and new additions to the guidance.
Industry group PhRMA, for instance, recommends that the FDA add more specific examples or literature references throughout “to provide detail to the high-level recommendations and to support the technical statements.” The FDA also should provide specific examples of where population PK data may alleviate the need for a postmarketing requirement or postmarketing commitment, PhRMA says.
Bayer, meanwhile, takes issue with the FDA’s inclusion of an executive summary in the population PK report that should focus on the key findings affecting approval or label decision or any other recommendation based on the population PK analysis.
“Although Bayer agrees that an executive summary could be beneficial, the population PK report is not the correct place. Clinical interpretation and label decision require, in general, an assessment of the all of the data e.g. the result of exposure response analysis and clinical safety and efficacy results of the pivotal study needs to be available. Very often population PK models are developed at different stages of drug development and reported earlier,” Bayer adds.
The company also raises the concern that the structure of the report will not be aligned with the European Medicines Agency and Japan’s PMDA guideline, as well as the general structure of clinical reports.
In addition, Astellas seeks further specifics from the FDA, noting that the draft includes “subjective and non-quantitative terms,” such as “adequate,” “sufficient,” “relevant” and “narrow.”
“While we appreciate that the Agency means for the guidance to be flexibly interpreted, more quantitative terms or suggested ranges would be appreciated,” Astellas says.
Pfizer proposes adding a new section to the draft, titled: “A. Scope of Data for Inclusion in Population PK Analysis” to discuss the use of data from healthy volunteer trials “to support the structural model and aid comparison between different populations before the current section A on study subjects and covariates.”
And Regeneron, among other comments, recommends restructuring the recommendations for the assessment of the effects of covariates “such that all discussions are pooled into a dedicated section specific to this topic. Such a section will provide Sponsors with a clear and concise resource to guide the writing of this component of the population PK report in preparation for applying for marketing authorization.”
RAPS: First published in Regulatory Focus™ by the Regulatory Affairs Professionals Society, the largest global organization of and for those involved with the regulation of healthcare products. Click here for more information.