Description
The examples provided in sections I.A through I.F of the ICH Q12 Annexes are mock examples provided for illustrative purposes. They only suggest how the tools described in sections III, IV, and V of the ICH Q12 guidance could be applied, and should not be used as a template or the sole basis for a regulatory submission. In addition, the reporting categories, as described in section II of the ICH Q12 guidance, may differ across regions depending on regional legislation; the nature of the product; and the Marketing Authorization Holder’s (MAH’s) demonstrated understanding of the product, process, and analytical procedure.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
3Identification of Established Conditions for the Manufacturing Process; Annex IA focuses on chemical medicinal products
Subject of the PACMP example
Identification of Established Conditions for the Manufacturing Process; Annex IB focuses on monoclonal antibody example
Stakeholders
3Entity responsible for managing the submission of PBRERs
Facility fee requirements for CMOs; CMOs qualifying for reduced facility fees
Marketing Authorization Holder responsible for safety reporting; Marketing Authorization Holder responsible for providing exposure data; Marketing Authorization Holder responsible for signal evaluation and reporting.; Marketing Authorization Holder responsible for presenting efficacy information
Regulatory Context
Regulatory Activities
5Post-Approval Change Management Protocol examples; Postapproval Change Management Protocol; Post-Approval Change Management Protocol for site transfers and process changes
Inspection by authorities requiring access to source records.; Access to source records for assessment of trial conduct
changes can be made with immediate or other notification to regulatory authorities
ICH guidelines standardized safety reporting and marketing application submissions
Applications consisting of combinations of development approaches
Document Types
3Document outlining ECs and reporting categories; PLCM document included in eCTD section 3.2.R; Document including proposed ECs and reporting categories; Appendix C example of a PLM document
prospective protocol should be prepared and approved internally
Format for submitting development information; Module 3 of the CTD for detailed descriptions of analytical procedures; ICH guideline M4Q(R1) for the registration of pharmaceuticals.
Attributes
10Input parameter for anion exchange chromatography
Performance characteristic assessed via linearity experiment
Closeness of agreement between a series of measurements from multiple samplings.; Performance characteristic measured by intermediate precision; Performance characteristic to be validated
Performance characteristic to be validated
Ability to detect intended mechanism of action without interference; Performance characteristic to be validated
Classification of CMC changes based on risk to product quality; Classification for making changes to approved ECs.
Legally binding information in a PLCM document
Input parameter evaluated for impact on CQAs
CPPs that can influence CQAs
A measurement of the relative proportion of particles in a sample as a function of size.
Technical Details
Substances
6examples of such components include but are not limited to the active moiety (API)
impact of changes should be assessed when switching to automated methods
Scope of manufacturing site transfers in Annex IE
Non-glycosylated recombinant protein used as a biological drug substance example
quantitation of HCP using USP <1132>
The antibody portion of an ADC, referred to as mAb
Testing Methods
10Used to examine samples for physical, chemical or biological changes
spectroscopic or chemical/physical property method
change acceptable where mode of separation remains the same
Used for detection of capsid amino acid modifications.
Enzyme-linked immunosorbent assay technique
Example of an analytical procedure physicochemical basis
Used to demonstrate comparability for site transfers
Initiated on commercial-scale batches at alternate sites
Used in series with mass spectrometry
NIR probe used for data collection and PAT
Processes
9Changes to this process may affect the identity and NDI status of an ingredient.; Changes to this process may create an NDI; you should describe the manufacturing process and provide detailed information; includes fermentation as an intrinsic part of identity
Completed prior to implementation of a new manufacturing site
system for designing, analyzing, and controlling manufacturing
Unit operation used as an example for EC identification; Unit operation defined as an Established Condition
Product performance test for an immediate release dosage form
Combining materials within the same specification to produce a homogeneous intermediate or API
one of the two steps focused on in the biological example
unit operation in the manufacturing process
Unit operation discussed for lifecycle management and established conditions
Clinical Concepts
2not warranted as a result of the method change
Presence of clinical data determines whether a full or half application fee is assessed.
Identified Hazards
Hazards
4risk in multidose drug products
Testing excluded from the simplified analytical change approach
Output attribute considered an EC in minimal approach
microbiological contamination risk in bulk solution
Standards & References
External Standards
2Methods described here are excluded from the structured approach to changes
recognized standard reference for analytical methods
Specifications
4limits for solid state form and particle size; Tightening acceptance criteria; Numerical limits or ranges for tests
Criteria for determining if a chromatographic system is functioning properly
Acceptance criteria limit of maximum 5.0%
May be more stringent than shelf life specification
ICH References (4)
Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management; referenced for established conditions and life cycle management tools; in line with recommendations described in ICH Q12; Guideline for technical and regulatory considerations for pharmaceutical product lifecycle management; Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management.
Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process
Quality Risk Management recommended for combination products
discussed in relation to validation and analytical procedure control strategy; Validation of Analytical Procedures guideline used for RTRT validation; Guideline for validation of analytical procedures
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