By Karen Sitney AbbVie Rashmi Rawat AstraZeneca Beatrix Metzner Boehringer Ingelheim Li Cui Daiichi Sankyo Orna Wisniak Desai Ferring Nicole Lundberg GSK Sejal Gandhi Roche Kimberly Cheung Sanofi Rachel Thornton UCB Isabelle Lequeux AbbVie
Published in: BioPhorum Operations Group Ltd
Published on: July 9, 2024
In this paper ‘cumulative stability’ is defined as the concept of linking the stability of a drug substance (DS), drug product (DP) and/or of a manufacturing intermediate to the subsequent step(s) of the product manufacturing process. It may also be referred to in industry as ‘end to-end stability’. The biomanufacturing industry is facing a regulatory requirement divergence with regards to cumulative stability data in both new and major post-approval submissions. There is a lack of clarity in regulations and guidelines as to what data are required or expected to ensure successful regulatory filings. In most cases where cumulative stability is requested, regulatory expectations focus on linking the stability of the DS to that of the DP by manufacturing a batch of DP from aged DS and evaluating its stability until the end-of-shelf-life. However, additional evidence on other stability studies linking different stages of the manufacturing or lifecycle of products has also been requested. Through BioPhorum, a team of SMEs from the pharmaceutical industry (27 SMEs from 17 organizations) convened and participated in a series of workshops aimed at defining cumulative and other stability studies requested by regulators, and compiling their best practices and recommendations. To gather more data regarding the perceived differences in regulatory expectations, the team first conducted a survey. Subsequently, the team discussed and defined their recommended strategies based on risk assessment, and knowledge and understanding of the product and process.
