ICH Q1B Photostability Guideline – Time for a Revision?
Steven W. Baertschi, Ph. D. et al.
The presentation was based on a recent publication in the Journal of Pharmaceutical Sciences (99:7, 2934-2940, 2010). This oral presentation highlighted some significant and some not so significant deficiencies with
the ICH Q1B guideline on photostability, which was published in November 1996 and has been implemented in all three regions
(US, EU, and Japan). The presenters noted that since publication in 1996, the guideline has provided a useful basic protocol
for testing of new drug substances and associated drug products for manufacturing, storage, and distribution; the authors
also noted that the guideline does not cover the photostability of drugs under conditions of patient use. While there were
several areas within the guideline that would benefit from revision, a couple of notable issues were highlighted during the
First, the authors noted two significant problems with the Option 2 UVA and visible lamp choices. The cool white fluorescent
lamps currently in use in general do not match the spectral power distribution required by the guideline, as specified by
ISO10977. Further, the presenters assert that the UVA lamps commonly found in “ICH compliant” photostability chambers often
do not meet the requirements of Q1B (where Q1B specifies “A near UV fluorescent lamp having a spectral distribution from 320
nm to 400 nm with a maximum energy emission between 350 nm and 370 nm; a significant proportion of UV should be in both bands
of 320 to 360 nm and 360 to 400 nm”). Second, the authors showed that the current recommendation of quinine as an actinometer
should be specified only for a specific Option 2 UVA lamp. Further, the timing of absorbance measurements is absolutely critical,
since the quinine continues to react after the UVA source has been turned off at approximately one-fifth the rate of when
the light is on. The authors provided examples and literature references for their assertions.
The presenters called for the revision process, noting that nearly all of the Quality guidelines have undergone one or more
revisions, including the parent Stability guideline, which has undergone two revisions since its first version.
Designing Stability Studies for Global development Programs
Bekki Komas, B.S.
Day one of the Stability workshop included a presentation on Global stability requirements beyond ICH requirements. A recommendation
for a global approach to stability and case studies on post approval changes and Emerging Market draft guidelines were shared.
The ICH and WHO stability guidelines were shared at a high level. The discussion included information about countries where
actual practice is different than the WHO recommendations, for example Ecuador, Bolivia, Nigeria, Peru and Venezuela.
Recommendations for a global stability approach for drug substance supporting all markets was shared. Additionally, a drug
product stability decision tree with consideration of the stability of the product, and the countries where the drug is marketed
provided a clear recommendation for long term and accelerated stability conditions. Current emerging market draft guidelines
including the draft ASEAN Stability and Variations guidelines and challenges with those guidelines were outlined for group
A case study for CMC Post Approval change with technology transfer from development to a commercial site and included two
multivariate analysis models for stability and design space. Acceptance of the risk based approach and prior knowledge resulted
in stability requirement waivers and enabled a different approach to process validation. Key messages from the presentation
included that regional stability guidance exists for emerging markets and may be different than what is published in the WHO
Stability Guideline. Science and risk based approaches are not always accepted. Some new guidelines indicate an acceptance
of stability commitments instead of upfront data for process changes. The ICH Global Cooperation Group which includes 6 regional
harmonization initiatives APEC, ASEAN, Global Cooperation Council, PANDRH, SADC East Africa Community are making improvements