Description
This guidance is intended to provide recommendations to sponsors and applicants on the use of monoclonal antibodies (mAbs) as reagents in the manufacture of drug substances that are regulated by the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). The guidance focuses on the chemistry, manufacturing, and control (CMC) issues that should be addressed in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), supplements to these applications, or investigational new drug applications (INDs).
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
4Circumstance where a mass balance study might not be recommended
Testing recommendations for antibodies with product contact
Subject of comparability guidance
Included in the scope of comparability demonstrations
Stakeholders
2responsible for justifying omission of studies
entity submitting marketing applications
Regulatory Context
Regulatory Activities
5New Drug Application
Abbreviated New Drug Application
Biologics License Application
Investigational New Drug submissions
Submissions requiring supporting documentation for manufacture
Document Types
3Permits FDA to reference an existing IND
Type II drug master file incorporated by reference
documentation of sampling and testing results
Attributes
2primary emphasis for mAb reagents
Required label element for outsourcing facilities
Technical Details
Substances
3quantitative measurement of the major component(s) in the drug substance; changes in the synthesis of the drug substance
monoclonal antibody used as a reagent in drug manufacturing
The primary subject of the development and manufacture guidance
Testing Methods
5Enzyme-linked immunosorbent assay technique
Sodium dodecyl sulphate polyacrylamide gel electrophoresis
High-Performance Liquid Chromatography used for impurities or assay.
IEF profile for identity testing
Facilities solely engaged in testing do not incur facility fees
Processes
6method for generating mAb reagents
method for generating mAb fragments in bacteria
Preferable to rely on purification processes to remove impurities
description used to assess potential impact on biological safety, quality, and purity
purification of drug substance by mAbs attached to a solid support
The process for which all components must be listed
Identified Hazards
Hazards
3Safety concern regarding viral contamination
protein and DNA contaminants, column leachables, media components
hazard associated with animal food facilities
Standards & References
External Standards
1Points to Consider 1997 established standards for mAbs intended for human use
Specifications
3performance characteristic of the mAb reagent
ability to assess unequivocally the analyte in the presence of components which may be expected to be present
established by drug substance manufacturer for testing before use
Related CFR Sections (1)
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
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