Discover the key objectives of stability data package guidelines for Active Pharmaceutical Ingredients (APIs) and Finished Pharmaceutical Products (FPPs), including testing protocols and regulatory requirements.
The objective of these guidelines is to outline the minimum stability data package required for registration of Active Pharmaceutical Ingredients (APIs) and Finished Pharmaceutical Products (FPPs).
This set of directions superseded the 2016 WHO guidelines in that area. These benchmarks do not preclude alternative approaches to producing divisible dose formulations, so long as they are scientifically justified.
ICH and WHO guidelines relating to Multisource (generic) finished pharmaceutical products Active Pharmaceutical Ingredient Master File procedure, etc. supplement this guideline.
Scope of the Guidelines
These principles are in respect of new as well as existing APIs, informing the particulars necessary for an original application and subsequent applications undertaken by marketing authorization applicants in relation to their associated FPPs intended for human use. These recommendations would generally carry over to stability testing for biologicals, with special considerations for products of this type located in the ICH guidelines.
ICH guideline Q5C.
General Principles
Stability Testing is to provide evidence on the changes that quality of an API or FPP undergoes over a period of time under different environmental conditions such temperature, humidity and light. The stability testing program also studies product-related factors, including excipient, container-closure and packaging material interactions. For fixed-dose combination FPPs that contain more than one API, the interaction between different APIs should also be assessed.
The data obtained from stability testing can be used to provide a retest period for the API or a shelf life for the FPP and to recommend storage conditions. If a large change was observed under the test conditions then it is considered unstable.
Storage Conditions and Required Testing Interval
The guidelines specify storage conditions in climatic chambers for long-term, intermediate and accelerated conditions. It explains the frequency of testing, highlighting the necessity of determining the stability profile of the API, particularly for those having a proposed retest period or shelf life equal to or greater than 12 months
Stress Testing
Stress testing of the active substance can help identify the likely degradation products, which can in turn help establish the degradation pathways and the intrinsic stability of the molecule and validate the stability indicating power of the analytical procedures used. Stress testing is likely to be carried out on a single batch of the active substance. It should include the
effect of temperatures (in 10 °C increments (e.g., 50 °C, 60 °C, etc.) above that for accelerated testing), humidity (e.g., 75% RH or greater) where appropriate, oxidation, and photolysis on the active substance. The testing should also evaluate the susceptibility of the active substance to hydrolysis across a wide range of pH values when in solution or suspension. Photostability testing should be an integral part of stress testing.
The concept provides guidelines for API stress testing, to identify potential degradation products, and hence determine the probable degradation pathways.
Assessment and Stability Guarantees
Statistical analysis is performed on stability data while considering batch-to-batch variability.
Stability Commitments and the Need for Stability Studies: The guidelines provide different scenarios on when stability commitments are required, thereby stressing the need of continuing stability studies.
Conclusion
These guidelines give the overall flow of stability testing for pharmaceuticals which is required to maintain API’s and FPP’s (Active Pharmaceutical Ingredients & Finished Drug Products) quality, safety and efficacy through their shelf life(end).
They provide common standards and some flexibility according to the science but do adapt to international standardization through ICH.
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