Description
This guidance is a revision of the ICH guidance Q8 Pharmaceutical Development (Q8 parent guidance) that published in May 2006. In June 2009, the Q8 parent guidance was revised to add an annex, which provides further clarification of the key concepts outlined in the May 2006 guidance and describes the principles of quality by design (QbD). The Q8(R1) document issued in June 2009 includes the Q8 parent guidance and the annex. This second revision, Q8(R2), provides corrected captions for figures 2a and 2b in Appendix 2, section C.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
3Subject of the minor changes guidance
affect the dissolution rate of a tablet
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
4Stability package provided to support re-test period or shelf life; Initial filing requiring stability data; Initial filing where photostability information is required; Stability data provided with the regulatory submission; Where stability models and risk management descriptions are provided
Initiated by movement out of the design space
Submission for product approval
outside the design space would normally initiate a regulatory postapproval change process
Document Types
2Format for submitting development information; Module 3 of the CTD for detailed descriptions of analytical procedures; ICH guideline M4Q(R1) for the registration of pharmaceuticals.
Section of the CTD providing understanding of product and process
Attributes
10Attributes of the drug product to be considered during development
The end point for moisture content is 1-2%
Quality characteristic impacting tablet performance
Release of the drug substance from the intact or chewed tablets
Process inputs used to describe the design space.; measured material attributes used in real time release testing
A measurement of the relative proportion of particles in a sample as a function of size.
Physical, chemical, biological, or microbiological properties
Characterization of process parameters; Characterized ranges for process parameters.
identify any critical process parameters that should be monitored or controlled
QTPP impact should be considered in life cycle management.
Technical Details
Substances
2Postapproval 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
Differences in excipients may affect product stability
Testing Methods
10Part of stability testing parameters
Risk management method and tool (FMEA); A recognized risk management tool (FMEA).; FMEA provides for an evaluation of potential failure modes for processes and their likely effect on outcomes.
multivariate experiments used to investigate parameter interactions; Systematic method to determine the relationship between factors affecting a process.; Supporting justification of acceptable ranges.
Enhanced approach to validation in lifecycle management
Used for unit dose uniformity in-process testing.
studies available to validate the EDDO specifications
structured method for determining relationships between factors and output; design space can be explained mathematically through equations describing relationships between parameters
used to demonstrate effectiveness of preservative systems
performed for non-sterile drug products
Process monitoring for therapeutic proteins
Processes
7Scientific considerations for pediatric drug development; Developing appropriate formulations for each age group under PREA
Design space for granulation parameters
Drying the drug substance (e.g., changing from vacuum tray dryer to fluid bed dryer)
Physical modification that does not result in chemical alteration.; A process that does not typically chemically alter an ingredient
A key element of the pharmaceutical development section
Required for contaminated equipment and media before disposal
alternative approach to process validation
Identified Hazards
Hazards
3Risk associated with tattoo inks that can lead to infection.; Risk associated with insanitary conditions in tattoo ink preparation
operating below the lower limit of the design space can result in excessive particle attrition
Operating above the upper limit of the design space can cause excessive impurity formation
Standards & References
External Standards
1Process Analytical Technology tools utilized in enhanced approaches
Specifications
6An element of pharmaceutical development; prospective summary of the quality characteristics of a drug product
Volume is identified as a CQA in the manufacturing example
PAR established through univariate examination of a single parameter; Characterized range of an analytical procedure parameter resulting in meeting performance criteria.; Change of one or several parameters outside the already proven acceptable ranges.
limits for solid state form and particle size; Tightening acceptance criteria; Numerical limits or ranges for tests
scientific understanding to support the establishment of the design space; multidimensional combination of input variables and process parameters
Attributes typically associated with the drug substance quality are generally included in the drug product specification
ICH References (7)
Pharmaceutical Development
Principles of Quality by Design described within ICH Q8-Q11.; Pharmaceutical development guidance; Pharmaceutical development and CQA measurement during processing; Defines product lifecycle phases; Referenced for Critical Quality Attributes (CQA); Pharmaceutical Development.; General principles related to model development, validation and verification; Principles described in ICH Q8 apply to stability models; Pharmaceutical Development guideline mentioned regarding enhanced level of understandi
Organization of the Common Technical Document; Organization of the Common Technical Document for the Registration of Pharmaceuticals for Human Use
Quality Risk Management recommended for combination products
Referenced regarding specifications and solid state forms.
Specifications for biotechnological/biological products; Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products
Pharmaceutical Quality System
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