Stability Testing, PDF

Stability testing - purpose To provide evidence of how the quality of an API or FPP varies with time under the influence of environmental factors such as temperature, humidity and light. To determine a retest period (API) or shelf-life (FPP) over which the quality of the API/FPP can be expected...

Stability testing - purpose To provide evidence of how the quality of an API or FPP varies with time under the influence of environmental factors such as temperature, humidity and light. To determine a retest period (API) or shelf-life (FPP) over which the quality of the API/FPP can be expected to be acceptable (meets specs). 11/7/2024 Prof. Afaf ALNadaf 1 Basic data requirements (FPP) ✓Photostability testing on one FPP batch (exceptions) ✓Data on 3 FPP batches, at least 2 pilot scale third one can be smaller, if justified(exceptions): in the case of conventional dosage forms 2 pilot batches ✓Stability studies should be performed on each individual strength, dosage form and container type and size of the FPP unless bracketing or matrixing is applied. 11/7/2024 Prof. Afaf ALNadaf 2  Photostability As outlined in the WHO stability guideline, photostability testing should be conducted on at least one primary batch of the FPP if appropriate. If “protect from light” is stated in one of the officially recognized pharmacopoeias for the API or FPP, it is sufficient to state “protect from light” on labelling, in lieu of photostability studies, when the container-closure system is shown to be light-protective. Additional stress testing of specific types of dosage forms may be appropriate. 11/7/2024 Prof. Afaf ALNadaf 3  Minimum data requirements at time of submission (FPP) Study Storage condition Minimum time period Minimum data covered at registration by data at submission Long-term 30 °C ± 2 °C/65% RH ± 5% RH 6 months 12 months Accelerated 40 °C ± 2 °C/75% RH ± 5% RH 6 months 6 months 11/7/2024 Prof. Afaf ALNadaf 4  FPPs packaged in semi-permeable containers Study Storage condition Minimum time period covered by data at submission Long-term 25 °C ± 2 °C/40% RH ± 5% RH or 12 months 30 °C ± 2 °C/35% RH ± 5% RH Intermediate 30 °C ± 2 °C/65% RH ± 5% RH 6 months Accelerated 40 °C ± 2 °C/75% RH ± 5% RH 6 months 11/7/2024 Prof. Afaf ALNadaf 5  FPPs intended for storage in a refrigerator/freezer Study Storage condition Minimum time period covered by data at submission Long-term 5 °C ± 3 °C 12 months Accelerated 25 °C ± 2 °C/60% RH ± 5% RH or 6 months 30 °C ± 2 °C/65% RH ± 5% RH or 30 °C ± 2 °C/75% RH ± 5% RH Storage in a freezer Long-term -20 °C ± 5 °C 12 months 11/7/2024 Prof. Afaf ALNadaf 6  Stability testing CTD file Requirement Stability protocol Stability specifications Stress testing Long term conditions Accelerated conditions Stability studies In-use stability data (if applicable) Proposed shelf-life of FPP - commitment batches 11/7/2024 Prof. Afaf ALNadaf 7  Stability protocol Number of batch(es) and batch sizes Container closure system (s) Tests and acceptance criteria (reference to test methods) Conditions of storage Testing frequency 11/7/2024 Prof. Afaf ALNadaf 8 Specification Stability studies should include testing of those attributes of the FPP that are susceptible to change during storage and are likely to influence quality, safety, and/or efficacy. The testing should cover, as appropriate, the: physical, chemical, biological microbiological attributes, preservative content(e.g. antioxidant or antimicrobial preservative) and functionality tests (e.g. for a dose delivery system). 11/7/2024 Prof. Afaf ALNadaf 9  Notes For sterile products sterility should be reported at the beginning and end of shelf-life. For parenteral products, sub-visible particulate matter should be reported frequently, but not necessarily at every test interval. Bacterial endotoxins need only be reported at the initial test interval. Weight loss from plastic containers should be reported over the shelf-life. In-use periods (e.g. parenteral and ophthalmic products) should be justified with experimental data. 11/7/2024 Prof. Afaf ALNadaf 10 cont′d The orientation of the product during storage, i.e. upright versus inverted, may need to be included in a protocol where contact of the product with the closure system may be expected to affect the stability of the products contained, or where there has been a change in the container closure system. Generally only a consideration for liquids and semi-solids. 11/7/2024 Prof. Afaf ALNadaf 11 Stress testing Photostability: Studies should be conducted on at least one primary batch of the FPP; as ICHQ1B specific testing on certain products (e.g. metered dose inhalers, creams, emulsions, refrigerated aqueous liquid products): Freeze/thaw study for liquid products important if the drug product is at risk for experiencing temperatures