Description
This guidance is intended to address recommendations on the application of bracketing and matrixing to stability studies conducted in accordance with principles outlined in the ICH guidance Q1A(R) Stability Testing of New Drug Substances and Products (the parent guidance).
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
6Scope of the guidance
Scope of the guidance
Solubilized dosage forms where BA/BE may be self-evident
additional justification should be provided where there are a large number of potential drug-device interactions
Scope of the analytical procedures
Scope of the analytical procedures
Regulatory Context
Document Types
1Matrixing is the design of a stability schedule such that a selected subset of samples is tested.
Attributes
10Sampling variability controlled by the sample size of the study.
Evaluation of the proposed matrixing design with respect to its power to detect differences among factors in the degradation rates.
Supporting data could be supplied showing relative moisture vapor transmission rates.
Each storage condition should be treated separately under its own matrixing design.
Characteristics include oxygen permeation rate per dosage unit or unit fill volume.
Characteristics include container wall thickness, closure geometry, and water vapor permeation rate.
A design factor evaluated in stability studies
Administrative change requires unique SID for each container size
controls in place to maintain the strength, composition, and purity
Determined based on stability data; Established through stability testing; also called dating period.; Established through formal stability studies; Establishing the period during which a drug product is expected to remain within specifications; Period for drug products; The period during which a drug product is expected to remain within specifications; Duration product remains within acceptance criteria; Period during which product remains within specifications; Established for intermediates pu
Technical Details
Substances
2Differences in excipients may affect product stability
quantitative measurement of the major component(s) in the drug substance; changes in the synthesis of the drug substance
Testing Methods
3Where the supporting data exhibit moderate variability, a matrixing design should be statistically justified.
Testing used to justify leveraging data across products
plan for evaluating equivalent or improved performance
Processes
3Alternative approach to stability protocol design; A science- and risk-based reduced stability design strategy.; Matrixing is the design of a stability schedule such that a selected subset of samples is tested; The use of a matrixing design
Information contained in MFs; Processes described within a Master File.
Primary process described in the guideline; Core activity described in the guidance; General process for evaluating product quality over time; Formal stability studies to assess adjuvant stability; Evaluation of attributes at all storage conditions; The process of evaluating product quality over time under specified conditions.; Evaluation of product quality over time
ICH References (2)
Guideline on stability testing used to identify potential impurities.
Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- E11A Pediatric Extrapolation
- M15 General Principles for Model-Informed Drug Development
- Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product
- Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances
- Rare Diseases: Considerations for the Development of Drugs and Biological Products
- Q3C Impurities: Residual Solvents_2011
- Providing Regulatory Submissions in Electronic Format --Content of the Risk Evaluation and Mitigation Strategies Document Using Structured Product Labeling: Guidance for Industry
- Q4B Annex 5: Disintegration Test General Chapter