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
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
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
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.