An ancillary material supplier's perspective on ISO 20399:2022
Andrew Breite1, Robert C McCarthy1.
1Quality, VitaCyte LLC, Indianapolis, IN, United States
Ancillary material (AM) users are responsible for assessing the risks of AMs by qualifying the AMs used in these processes. Complex AMs, such as tissue dissociation enzymes, can profoundly impact cell-gene therapy (CGT) products. USP <1043> laid out a framework for a risk-based approach to qualify AMs. More recently, the ISO 20399:2022 AM Standard recommended that AM suppliers collaborate with AM users to support the qualification of their products for use in CGT manufacturing processes. The poster highlights the importance of the supplier-user relationship in managing the risks of AM used in CGT products.
The USP chapter and ISO Standard emphasize the importance of AM qualification in understanding how the AMs impact the CGT product's critical quality attributes. Qualification includes understanding how inherent AM variability impacts the CGT final product. However, AM specifications are often set by the supplier with limited input from AM users. Furthermore, AM variability is typically not part of suppliers' product documentation. AM users must request this information and rely on the cooperation of the AM supplier to understand the variables that may impact the CGT product.
The solution to this gap is for AM suppliers and users to develop a strong working relationship that enables users to apply the Quality by Design (QbD) framework to their manufacturing process. AM suppliers can work to mitigate risks identified by AM users to identify the AM critical material attributes. An example of potential responses to major risk categories is shown in the table below.
| Risk Categories | AM User Concern | AM Supplier Response |
|---|---|---|
| Safety | Aniaml origin materials | Develop a robust raw material qualifiction program based on the veriffiable traceability of all components. |
| Consistency | Potency variability |
Develop a deep understanding of the AM's manufacturing critical process parameters. Identify and control critical material attributes for robust CGT manufacturing. Utilize all appropriate validated characterization methods. |
| Sustainability | Reliability of supply |
Provide resources to plan for anticipated demand expectations. Invest in a robust and reliable supply chain for all process inputs |
The mechanism by which the AM supplier responds to the user concerns is through transparent, detailed documentation that supports the AM user qualification plan. This process starts with proactive efforts by both parties to build a trusted working relationship.
While the AM user is ultimately responsible for the qualification of process inputs and manufacturing control, AM suppliers can better facilitate this endeavor by partnering with users to ensure adequate quality system controls are in place and appropriate supporting documentation is provided to users. AM suppliers should be willing to build relationships with AM users that facilitate qualification as trusted suppliers to meet regulatory scrutiny of CGT manufacturing processes.
[1] Ancillary Materials, ISO, Qualification