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Registering innovative raw materials using QbD principles: Protein A resins

1 April 2023
Drug Substance
Jane Worthington
Global Change Facilitator

The Covid-19 pandemic showed that relying on sole sources of supplies is not a commercially valid strategy for biomanufacturers.

To improve this situation, one of BioPhorum’s critical actions was to look at scenarios when a raw material is not compendial, defined and registered (through its name, supplier, and part number), and there is a change required in the registered details. This is because it leads to a post-approval regulatory notification and review before the raw material’s implementation, which can take 6–14 months or more (for a major change).

This situation has led us to publish the BioPhorum approach to the registration of innovative raw materials using quality by design principles. This contains a best practice approach allowing future changes to be notified as minor and documented in the license holder’s pharmaceutical quality system. It also allows the changes to be notified to an agency in the product annual report for immediate implementation (with no review required).

The approach provides license holders with a pragmatic, simple and regulatory-acceptable solution to mitigate the regulatory challenges associated with a second source of supply for non-compendial materials.

The BioPhorum approach is exemplified through two case studies: the virus retentive filter (or viral filter) outlined in the paper above, and the Protein A resin used to manufacture monoclonal antibodies outlined in Appendix 2: Protein A Resins.

Usually, a single version of a Protein A resin is selected early in process development and is then carried through to final commercial filing. However, when you have constrained supply chain conditions or new resin technology drives you to change to a new Protein A resin, there is currently no standardized approach to the technical assessment and regulatory framework necessary for you to successfully implement an alternate Protein A resin. We have specifically addressed this issue in Appendix 2.

We selected Protein A resins because they are a typical example of a complex and innovative raw material for which technical improvements happen consistently through the efforts of resin suppliers. At the same time, implementing new Protein A versions in existing products may be a significant regulatory burden for you.

The most urgent issues for our members are linked to commercial products, so the approach in Appendix 2 is set in the context of your post-approval commercial support activities. A similar approach will be expected if you make a new submission, especially if your supply chain intelligence indicates that enhanced Protein A resins may be available or desirable in the future.

The paper illustrates how you can apply our approach and contains an introduction to Protein A, the process followed for identifying critical material attributes, and the controls and principles for registration that would give you future flexibility of supply.

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