The International Consortium on Innovation and Quality in Pharmaceutical Development (IQ) formed in 2010 is an association
of over 25 pharmaceutical and biotechnology companies with a mission to advance science-based and scientifically-driven standards
and regulations for medicinal products worldwide. In the June 2012 issue of Pharmaceutical Technology, a paper was provided which described the IQs Good Manufacturing Practices (GMPs) in Early Development working group (1).
This working group (WG) is focused on developing recommended approaches to applying GMPs in several areas of Early Phase CMC
development activities (e.g., Phase 1 to Phase 2a). A key premise of the GMPs in Early Development WG is that existing GMP
guidance documents for early development are vague and that improved clarity with options to meet GMP expectations would be
helpful. Although more prescriptive guidance is not advocated, the sharing of best practices in this paper is done herein
to advance innovation in drug product development by improving cycle times, while maintaining appropriate product quality
and ensuring patient safety.
A consequence of the absence of clarity surrounding early phase GMP guidance has been varied interpretation and application
of existing GMP guidance within different companies and regulatory bodies according to their own culture and risk tolerance.
Internal debates often result in conservative "one-size-fits-all" interpretations that rely on International Conference on
Harmonization (ICH) guidelines that are relevant to commercial product development and do not distinguish differences in practices
between early development and later-stage development (i.e., Phase 2b and beyond). A key driver of the IQ WG, therefore, has
been to collectively define the minimum acceptable practices within industry regarding GMP expectations in early development
that allow for added flexibility and that are consistent with existing guidance and statutes (2, 3).
As outlined in the introductory paper to this series, the efforts of the GMPs in Early Development WG have been focused into
the following four areas of Chemistry, Manufacturing, and Controls (CMC) activities: Analytical Method Validation, Specifications,
Drug Product Manufacturing, and Stability (1). The initial scope of these efforts has been limited to small-molecule development,
which support First in Human (FIH) through Phase 2a (proof-of-concept) clinical studies.
A series of whitepapers describing a recommended approach to applying GMPs in each of these areas is being published within
this journal. In past editions, approaches to Analytical Method Validation, and Manufacturing to support health authority
submissions were provided (4, 5); approaches to Specification setting will be published in the October 2012 issue of Pharmaceutical Technology.
In this paper, Part IV, stability needs are discussed. During early drug development, stability data can be generated to support
the manufacture and storage of clinical products to meet regulatory expectations for Investigational New Drug (IND), Investigational
Medicinal Product Dossier (IMPD), or Clinical Trial Application (CTA) filings and to help understand the product and process.
The authors illustrate some best practices for stability to support early phase clinical trials in this paper; however, some
companies may choose to do more, or possibly less, at their discretion and with appropriate science- and risk-based justifications
suitable for the phases and purposes of development. The GMP quality systems (e.g., chamber qualification, standard operating
procedures) used to support such studies are not the focus of this paper.