Qualifying Ancillary Materials
As part of GMP compliance, ancillary materials should be assessed under a qualification framework that reflects the level of risk presented by that material.
Product qualification should become more comprehensive throughout product development, and should assess material source, identity, purity, biological safety, and overall suitability of the specific material. Vendor qualification is also a necessary activity, where their GMP and materials testing programs should be audited.
US Pharmacopeia Chapter <1043> is a key guidance document when developing a risk-based ancillary materials qualification framework. Ancillary materials are broken down into four tiers according to their level of risk:
|Risk tier||Material type|
|Tier 1||Highly qualified materials with a demonstrable quality specification, such as licensed biologics, approved drug, cleared medical device, or materials approved for use as an implantable material. Examples include injectable recombinant proteins and antibodies.|
|Tier 2||Materials intended for use in drug manufacture that are well characterized and produced under GMP conditions. Examples include recombinant growth factors and cytokines.|
|Tier 3||Materials not intended for use as ancillary materials, often produced for in vitro diagnostics or research-grade applications. Require a higher level of additional qualification before use. Examples include tissue culture media and process buffers.|
|Tier 4||Materials that are not produced under GMP compliance or intended for use as ancillary materials in drug production. Can include toxic substances with known biological function, or complex materials with incomplete quality specifications, including animal-derived products. Examples include fetal bovine serum (FBS) and chemically-defined toxins.|
Adapted from US Pharmacopoeia Chapter <1043> Ancillary Materials for Cell, Gene, and Tissue Engineered Products
Best practice guidelines suggest that where possible, licensed biologics, approved drugs, or cleared medical devices (Tier 1) should be adopted as ancillary materials. As one moves into higher tiers, a greater degree of qualification and testing must be put in place. It is therefore advisable to minimize the use of high-risk materials.
|Performance in the intended application||X|
|Provide CoA, CoC, CoO for AM||X|
|Verify country of origin to assure AM is safe with respect to source-relevant animal diseases (e.g. BSE/TSE)||X||X|
|Conduct a risk assessment for use of AM, based on information provided by supplier, or in collaboration with the supplier, for example, failure modes and effects analysis||X|
|Establish and implement qualification plan for AM||X|
|Confirm CoA test results critical to the cell product (e.g., functional assay)||X|
|Characterization testing of AM and set specifications (e.g., identity, purity, functionality, viral contamination,,animal origin, etc.)||X||X|
|Assess effect of lot-to-lot variation if AM in the final cell product||X|
|Determine if biocompatibility, biodistribution, cytotoxicity or adventitious agent testing is needed (or testing results might be available from supplier, if applicable)||X|
|Assess presence of residual AM in final cell product||X|
|Assess stability of AM||X||X|
|Qualify the supplier of the AM (e.g., supplier audit)||X|
|Execute quality and supply agreement||X||X|
|Implement higher manufacturing standards, custom formulation or replacement of substandard components||X||X|
|Inform the user of any changes in the manufacturing process of the AM or design/formulation of the AM (eg, under a quality agreement)||X|
|Prepare and submit a master file (DMF eCTD) for AM, if applicable||X|
Adapted from Solomon et al. 2016.