Korencic, Anja (2024) Position Statement in Support of Cell Bank Stability Monitoring from a Single Storage Location of Equivalent Storage Condition. BioPhorum.

Abstract

Evidence of stability of cell banks, used as a starting material for medicinal biotech products, under defined conditions of long-term storage is one requirement to ensure cell substrate stability per ICHQ5D and WHO TRS 978 Annex 3. Storing cell banks at appropriate storage conditions serves to halt molecular movement and biological activity, thus maintaining the cell banks' stability attributes, such as stable cell viability and growth upon reconstitution.
A stability monitoring program verifies this and ensures continuous quality oversight.
Stability monitoring programs are based on pre-defined bank-specific criteria. Representative data including all stability relevant parameters for a Master Cell Bank (MCB) are generated by initial characterization, production of clinical or commercial material or preparation of a new Working Cell Bank (WCB). Belonging data for WCB are generated from thaws for a clinical or commercial production campaign or appropriately documented scale-down or pilot-scale processes. Cell bank stability can also be monitored at a pre-defined interval in case no suitable thaws take place.
In alignment with ICHQ5D, redundancy in the storage of cell bank containers applies for MCB and WCB storage to provide protection from catastrophic events and to ensure continuous, uninterrupted production of pharmaceuticals. Common redundant storage strategies include storing portions of a single cell bank in different freezers, various physical locations within one site, or storing a portion of the cell bank at a redundant site.
It is common practice across the industry not to include the evaluation of cell bank vials stored at all redundant storage sites as part of the stability monitoring program. Redundant storage sites abiding by the same storage condition requirements and equivalent quality management system are equivalent in function, ensuring comparable and stable quality of cell banks across all sites.
This approach is justified by the following rationales:
Storage equipment is qualified, monitored and suitable for cell bank storage at the appropriately defined temperatures for the respective cell bank type. Operational parameters like temperature ranges and alarm limits are in place according to cell bank storage specifications. At all locations, operation and maintenance of storage equipment follow defined procedures, leading to an equivalent operational status of the equipment. Inventory oversight, routine documentation of withdrawals and entries as well as access control are in place at each redundant site according to the GMP standard for maintaining the cell banks' quality attributes.
Cell bank transportation for long-term storage takes place in qualified shipping containers and by qualified delivery companies under the same conditions as long-term storage. Transportation controls are in place to ensure temperature is maintained within specification throughout the transfer. Excursions of storage and shipment temperature, which might occur at all redundant storage locations, are assessed in the quality system for product quality impact, root causes and potential corrective actions.
In summary, incorporating stability monitoring for all redundant storage sites will lead to quicker depletion of cell banks which are intended to support production of clinical and commercial material, while generating data of no additional informative value to evaluate the storage stability of a cell bank. Under equivalent storage and quality management procedures, the quality of cell banks stored at redundant locations should be considered comparable due to the aforementioned reasons.

Item Type:	Article
Date Deposited:	29 Jun 2024 00:45
Last Modified:	29 Jun 2024 00:45
URI:	https://oak.novartis.com/id/eprint/53468