Pharmaceutical Stability: Scientific and Regulatory Considerations for Global Drug Development and Commercialization - Pharmaceutical Technology

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Pharmaceutical Stability: Scientific and Regulatory Considerations for Global Drug Development and Commercialization
A two-day workshop on the "science behind pharmaceutical stability" was held in conjunction with the Annual Meeting of American Association of Pharmaceutical Scientists (AAPS) on Oct. 21-22, 2011 in Washington, DC.

Effective Approaches for Conducting Method Transfer

Kim Huynh-Ba, M.Sc.

Analytical procedures are critical to determine quality of pharmaceutical products at release and throughout their shelf life. Kim Huynh-Ba discussed several options to transfer analytical procedure from one laboratory to another laboratory and effective approaches to be considered when conducting method transfer. Method transfer is a process of which an analytical laboratory is qualified to perform a testing procedure, as method transfer activity is required as part of method validation. This training of performing an analytical procedure is done by The Transferring Lab to The Receiving Lab. It is well documented that there are four options that can be used for this purpose. Three of these four options involve lab activities and the selection depends on the validation status of the analytical procedure and/or availability of lab personnel. These are: Comparative Testing, Co-Validation and Re-Validation. The fourth option is to determine if the Transfer Waiver can be done. Several references including USP new General Chapter <232> 1224 — have suggested this option. Based on the knowledge, ability and experience of the Receiving Site, additional testing may not be needed to qualify The Receiving Lab to perform certain analytical procedure.

As all other cGMP activities, transfer activities are conducted according to a protocol with predetermined acceptance criteria. This protocol should be agreed upon by all sites involved. Elements of a transfer process were also discussed. Depending on the types of labs involved, certain SOPs such as data review, data reporting, OOS or OOT investigation from both sites should be discussed prior to the transfer. Conclusion of the transfer must be documented with all data reported including any representative chromatogram or spectra. It is important that validation data are available to the Receiving Lab as part of the Transferring Background Package and The Receiving Lab must conduct a thorough gap analysis before any testing can be done. It is also advised to avoid cGMP materials to be used for transfer activities to avoid issue that may arise with data generated.

Roundtable Discussion – Interesting and Challenging Stability-Related Regulatory Questions

Panelists: Stephen Colgan, Ph. D.; Robert J. Timpano, B. S.; Ganapathy Mohan, Ph. D.; David Lin, Ph. D.

Day one of the workshop concluded with a Roundtable discussion that focused on Regulatory Queries. A quick show of hands at the beginning of the Roundtable indicated that the areas of most interest included Science and Risk-Based Approaches to Stability/Shelf-life and Stability Protocols.

It was noted that the FDA has been advocating biorelevant specifications, but do not appear to embrace biorelevance when it comes to stability protocols. An example is the mandate to include water content in post-approval proposals when the science clearly indicates that water content has no relevance to stability or biorelevance. The panel noted that there is no guidance in this area, but encouraged the audience to use science to support stability testing protocols. It also was noted that scientific engagement with the regulators in the ICH regions would be welcomed, this is not the case for most of the Emerging Market regions.

The discussion continued with a discussion of science-based stability protocols that should only focus on the relevant product attributes. This approach would be leaner, and would protect the patient as well as non-lean protocols. The panel noted that the Quality Target Product Profile (QTPP) could be leveraged to advocated Lean Stability Protocols.

The most enthusiastic discussion of the Roundtable focused on a liquid product in a semi permeable or non permeable container and whether a matrixed stability protocol would be suitable for containers stored upright, upside down, and lying down. The panel noted that developing a matrixed protocol can be difficult and recommended that a statistician be engaged. It also was suggested to review this type of protocol with the Regulatory Authorities before execution. From a scientific point of view, the panel noted that a Stability Risk Assessment would help define what attributes should be monitored on stability and whether a matrixed approach should be considered. For the question on container orientation, the stability scientist should determine what attributes may be affected by the container orientation. If there is a medium or high risk that the orientation would have an affect on a potential shelf-life limiting attribute, a matrixed approach would not be advisable. In the end, everyone agreed that science and a knowledge of the regulations should be the drivers when stability protocols are being developed.


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