Description
This guidance provides recommendations to assist industry and other stakeholders involved in the development of bispecific antibodies. In addition to general considerations, the guidance provides recommendations for specific regulatory, quality, nonclinical, and clinical considerations for bispecific antibody development programs. Although this guidance is intended for bispecific antibodies, the principles discussed in this guidance may also inform the development of other types of bispecific protein products and multispecific products. This guidance does not discuss development considerations for other multitarget therapies that are antibody cocktails, polyclonal antibody products, or combinations of monoclonal antibodies.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
3Therapeutic product that targets three or more antigens
Anti-TNF-alpha drug substance and drug product
Genetically-engineered, recombinant antibodies that consist of two distinct binding domains; A single molecule antibody that targets two different antigens or epitopes.
Stakeholders
3Entity responsible for submitting applications under section 524B
Entities involved in the development of bispecific antibodies
Guidance for Industry
Regulatory Context
Regulatory Activities
1Selection of initial dose for clinical trials.
Attributes
1On- and off-rates of each arm for its target.
Technical Details
Substances
1Targets for certain categories of bispecific antibodies.
Testing Methods
1Adventitious virus testing using indicator cell lines; Assays performed on permissive cells for MCB and virus seeds.
Processes
4implied manufacturing process under QS regulation
Specific clinical considerations mentioned in the table of contents
The purpose of this guidance is to help sponsors in the clinical development of drugs.
Scientific considerations for bispecific antibody programs
Clinical Concepts
5Assessment of the immune response to the biological product
Conditions treated by therapeutic monoclonal antibodies
Conditions treated by therapeutic monoclonal antibodies
Conditions treated by therapeutic monoclonal antibodies
target disease for the combination drugs
Identified Hazards
Hazards
1Risk associated with homodimers of anti-CD3 engaging arms.
Standards & References
Specifications
1Specific ability or capacity of the product to effect a given result
ICH References (3)
Nonclinical Evaluation for Anticancer Pharmaceuticals; Guideline regarding pharmaceuticals for advanced cancer.
Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals; guidance regarding nonclinical immunotoxicity assessment of biopharmaceuticals
The Common Technical Document (CTD)—Efficacy.
Related CFR Sections (1)
- 21CFR300.50§ 300.50 Fixed-combination prescription drugs for humans.
The Food and Drug Administration's policy in administering the new-drug, antibiotic, and other regulatory provisions of the Federal Food, Drug, and Cosmetic Act regarding fixed combination dosage form prescription drugs for humans is as follows:Read full regulation →
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- How to Prepare a Pre-Request for Designation (Pre-RFD): Guidance for Industry (Status: Final)
- Development of New Stereoisomeric Drugs (Status: Final)
- Format and Content of the Clinical and Statistical Sections of an Application (Status: Final)
- Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms — Recommendations for Clinical Evaluation (Status: Draft)
- Gingivitis: Development and Evaluation of Drugs for Treatment or Prevention (Status: Draft)
- Helicobacter pylori-Associated Duodenal Ulcer Disease in Adults: Developing Drugs for Treatment (Status: Draft)
- Influenza: Developing Drugs for Treatment and/or Prophylaxis (Status: Final)
- Codevelopment of Two or More New Investigational Drugs for Use in Combination (Status: Final)