Stability testing to support distribution of temperature-sensitive pharmaceuticals
Robert H. Seevers
This presentation discussed the other types of testing which may be conducted in addition to the standard ICH conditions that
permit a stability budget to be created for a pharmaceutical. Besides using data from long-term and accelerated testing such
as that provided for in the ICH guidances, the speaker proposed adding freeze-thaw and temperature cycling studies to create
a fuller picture of a drug's susceptibility to temperature changes during the entire distribution process from manufacture
to transport, storage, and end use. It was shown that the concept of time out of refrigeration, which allows for room temperature
operations such as packaging and labeling of refrigerated products, can be expanded to the entire distribution process.
Effective approaches for conducting method transfer
Method transfer is a process of which an analytical laboratory is qualified to perform a testing procedure as part of method
validation. The speaker discussed the options of transfering analytical procedures from one laboratory to another and effective
approaches to be considered when conducting method transfer. Transfer activities are conducted according to a protocol with
predetermined acceptance criteria agreed upon by all sites involved. This includes certain SOPs such as data review, data
reporting, and out-of -specification (OOS) / out-of-trend (OOT) investigation from both sites. Conclusion of the transfer
must be documented with all data reported. 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
Interesting and challenging stability-related regulatory questions: a roundtable discussion
Panelists: Stephen Colgan, Robert J. Timpano, Ganapathy Mohan, and David Lin
The roundtable discussion was focused on regulatory queries, with science and risk-based approaches to stability/shelf-life
and stability protocols being of particular interest. Firstly, it was noted that FDA does not provide guidance on biorelevance
in stability protocols; the audience was, however, encouraged to use science to support stability testing protocols. Secondly,
whilst scientific engagement with the regulators in the ICH regions would be welcomed, this is not the case for most of the
emerging market regions. There was also a discussion that science-based stability protocols should only focus on the relevant
product attributes because 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 was on a liquid product in a semi-permeable or non-permeable container and the suitability
of a matrixed stability protocol for containers stored upright, upside down, and lying down. Developing a matrixed protocol
can be difficult and the panel recommended reviewing the protocol with the regulatory authorities before execution. From a
scientific point of view, the panel noted that a stability risk assessment would help define attributes that should be monitored
for stability, including effects of container orientation, and determine whether a matrixed approach was required. It was
agreed that science and knowledge of the regulations should be key drivers when developing stability protocols.
Dilip R. Choudhury, PhD,* is with Allergan and can be reached at firstname.lastname@example.org
, tel: 714.246.2288. Additional contributors:
Ramesh K. Sood, PhD, is with FDA; John Bobiak, PhD, is with Bristol-Myers Squibb; Mark Alasandro, PhD, is with Allergan, Inc., Steven W. Baertschi, PhD, is with Elli Lilly and Company; Bekki Komas, is with Glaxo Smith Kline; M. J. Skibic, PhD, is with Elli Lilly and Company; Brian W. Pack, PhD, is with Elli Lilly and Company; Saji Thomas, is with Par Pharmaceuticals; Robert H. Seevers, PhD, is with Eli Lilly and Company; Kim Huynh-Ba, is with Pharmalytik; and Stephen Colgan, PhD, is with Pfizer.
*To whom all correspondence should be addressed.
1. S.W. Baertschi, K.M. Alsante and H.H. Tonesen, J. Pharm. Sci.
99 (7) 2934–2940 (2010).
2. M.J. Skibic et al. J. Pharm. Biomed. Analysis.
53 (3) 432–439 (2010).