Cell banks represent the fundamental starting substrates for biological drug substance/drug substance intermediate manufacturing. So, the availability of well-characterized cell banks capable of supporting manufacturing processes is critical for an uninterrupted drug product supply to patients and global markets.
This is why two-tier cell banking systems are developed, consisting of master cell banks and working cell banks (WCBs). Although WCB inventories (e.g., vials, ampoules, bags, etc.) are usually developed with a plentiful supply, it is often necessary to replenish them to meet product demand.
However, many countries’ regulatory requirements for introducing replenishment WCBs are highly variable around supporting data and reporting categories. This results in inconsistent expectations among different health authorities.
BioPhorum’s new paper, A risk-based scientific approach to qualify replenishment working cell banks, an industry view, aims to ensure a consistent cross-industry expectation for an acceptable replenishment WCB qualification strategy using a risk-based scientific approach.
De-risking product supply
This will enable appropriate planning and agile operations, and de-risks product supply for patients by preventing possible delays when replenishing WCBs.
The paper examines the various scenarios when replenishment WCBs are manufactured, including when they are replenished and introduced according to the initially registered process (‘like-for-like’ replenishment). It also highlights changes to cell bank manufacturing and materials that can occur during replenishment.
After assessing the impact on product quality, the paper proposes an appropriate qualification and regulatory filing strategy in each case, which considers the potential effects on cell bank growth and viability performance.
Driven by a lack of technical drivers and continuity of product supply risks, the team has made a series of globally applicable recommendations. These relate to WCBs for all biologics developed using a parental cell line/host strain that has been transfected with the genetic material to express the desired protein of interest (or, in the case of vaccines, using native strains or parental cell lines expressing antigens).
This paper will help the industry harmonize towards a risk-based categorization of post-approval changes, which is a critical step to meet the objectives of ICH Q12: Technical and regulatory considerations for pharmaceutical product lifecycle management.