Description
This guidance is the second revision of Q1A Stability Testing of New Drug Substances and Products, which was first published in September 1994 and revised in August 2001. The purpose of this revision is to harmonize the intermediate storage condition for zones I and II with the long-term condition for zones III and IV recommended in the ICH guidance Q1F Stability Data Package for Registration Applications in Climatic Zones III and IV. The changes made in this second revision are listed in the attachment to this guidance.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
2Mass balance studies should be conducted for all new molecular entities
RTRT and CTD sections apply to drug products
Stakeholders
1Entity submitting development data and knowledge; Entity performing the work process for change
Regulatory Context
Regulatory Activities
2data which should be presented in a registration application
A commitment to continue stability studies post-approval
Document Types
2Post-approval stability protocol changes
Cybersecurity information should be included in device labeling
Attributes
10Derived from climatic data to define testing conditions; Single derived temperature affording the same thermal challenge as a range of temperatures
Acceptable variations in temperature and relative humidity
conclusions regarding appropriate storage conditions and an appropriate retest or expiration date; a retest date allows for use of a material beyond the retest date
A batch manufactured at production scale using production equipment in a production facility.
A batch used in a formal stability study from which data are submitted in a registration application.
A batch manufactured by a procedure fully representative of a full production scale batch.
should be based on appropriate supportive stability data
Measured at specific relative humidity and temperature to assess semipermeable containers.
Long-term, accelerated, and intermediate conditions
proposed for a drug substance; Proposing a retest period or shelf life based on attribute assessment; period established for drug substances based on stability data
Technical Details
Substances
3Postapproval changes to drug substances; the active pharmaceutical ingredient being modified; Evaluation of physical properties for drug substance; Active ingredient intended to furnish pharmacological activity; The molecule or ion responsible for the physiological or pharmacological action.; The active pharmaceutical ingredient subject to postapproval changes
Drug type that may alter the minimum acceptable size of the safety database
Component used in human and animal drugs
Testing Methods
9Used to suggest potential for photoreactivity
Product testing after storage under exaggerated conditions
The process of adding together the assay value and levels of degradation products.
Stability studies under the recommended storage condition for the retest period or shelf life.
Studies conducted at 30°C/65% RH designed to moderately increase the rate of chemical degradation.
Used to demonstrate that results of testing are poolable for grouped sensors
used to represent the relationship between an attribute and time
study designs generally inappropriate for recombinant protein products
study designs generally inappropriate for recombinant protein products
Processes
10Alternative approach to stability protocol design; A reduced stability design testing only extremes of certain factors.; An example of a bracketing design is given in Table A1-1; If a bracketing design is utilised
Long-term and accelerated studies undertaken on primary and/or commitment batches.
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
Testing to identify degradation products and pathways; Studies undertaken to elucidate intrinsic stability of drug substances or medicinal products
Purpose of photostability testing for drug substances.; Evaluation of light exposure effects on product efficacy; Systematic approach to testing light-sensitive products; Required if product is sensitive to light exposure; Testing for light sensitivity in reduced protocol designs
40°C ± 2°C / 75% RH ± 5% RH
25°C ± 2°C/60% RH or 30°C ± 2°C/65% RH
30°C ± 2°C / 65% RH ± 5% RH
Testing conducted to ensure expiration dating and storage conditions
Studies designed to increase the rate of chemical degradation or physical change using exaggerated storage conditions.
Standards & References
Specifications
8Confirmed by 3 months of stability data
Tests and acceptance criteria determining suitability throughout retest period or shelf life.
Combination of tests and acceptance criteria determining suitability at the time of release.
Specific limits used to define specified or unspecified impurities.
establish a retest period for the drug substance
Criteria for security architecture and design outputs.
Criteria to ensure quality through the end of shelf life
Defined as 5 percent change in assay or failure to meet physical attributes
ICH References (9)
Stability Testing of New Drug Substances and Products
Stability Data Package for Registration Applications in Climatic Zones III and IV.
Quality of Biotechnological Products: Stability Testing
Stability Testing for New Dosage Forms
Photostability Testing of New Drug Substances and Products
Referenced regarding specifications and solid state forms.
Specifications for biotechnological/biological products; Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products
impurities in new drug substances; Referenced regarding impurities and polymorphism.
impurities in new drug products; Impurities in new drug products; Recommendations for genotoxicity studies and toxicological qualification; Impurities in New Drug Products; Qualification study(ies) as described in ICH Q3B
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