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.




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 talk.

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 discussion.

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 towards harmonization.


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