As discussed in a recent Lachman blog Revised Q1 Draft Stability Document Issued by FDA, the draft guidance titled Q1 Stability Testing of Drug Substances is a consolidated revision of ICH Q1A(R2), Q1B, Q1C, Q1D, Q1E, and Q5C. This draft guidance provides guidance on product categories, such as advanced therapy medicinal products, vaccines, and other complex biological products including combination products that were not previously covered under the existing ICH stability guidances.
One of the upgrades in the proposed guideline is a detailed section on Protocol Design for Formal Stability Studies (Section 3). In the current ICH guidelines, there is a requirement for stability protocols; however, there are no specific details provided around the design and lifecycle of the stability protocol itself. The proposed stability protocol process flow for development, design, and execution is presented in Figure 2 of the draft ICH guideline as a flow diagram, which is provided below.
The proposed guideline is organized in such a manner that it leverages knowledge gained from long-term and accelerated stability studies performed earlier in development, plus development studies conducted under stressed and forced conditions. The knowledge and understanding from development should lead to the identification of Critical Quality Attributes (CQA) that may have a potential to be stability indicating under appropriate storage conditions. This knowledge would be used to support the formal stability study design. During the product’s lifecycle, further knowledge is gained that may be used to optimize the stability protocol design. In other words, if the data for a specific CQA does not change over the retest period/shelf life of the product, then the stability protocol supporting the product lifecycle may be updated accordingly.
Companies are likely already addressing the protocol development element per this draft guidance under product/analytical method development. Typically, stability procedures focus on the protocol content, such as the purpose of the study, time points, tests to perform and when, samples required, product description, etc., but with little or no direction around product knowledge.
The proposed draft guidance is lengthy and it will likely take some time for you to digest it in its entirety so it is best to get started reading one section at a time. If you have any questions concerning the draft ICH stability guidance and how to implement it in your firm, please reach out to us at LCS@LachmanConsultants.com.
