Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
4Assessment of embryo-fetal developmental toxicity; Small molecules, biotechnology-derived products, and related compounds
Focus of biologics DDI evaluation.
Principles may be applicable to these products
Animal models expressing the human receptor used for safety testing
Stakeholders
3Entity responsible for submitting NDINs
Often the only relevant species for certain classes of compounds
Species in which the test material is pharmacologically active
Regulatory Context
Regulatory Activities
9Standard bioassays are generally inappropriate; product-specific assessment needed
Evaluation of the formulation intended for marketing
Submission requiring RVLP quantification data; Requires data from at least three lots of purified bulk
Regulatory procedure involving electronic exchange of documents
Used to describe dose-response relationships and systemic toxicity
Conducted to evaluate reversal or worsening of toxicological effects
Evaluation of potential immunogenicity and immune system effects
Dependent upon product, clinical indication, and patient population
Standard range and type are generally not applicable to biopharmaceuticals
Document Types
1Issued by regulatory agencies regarding safety assessment
Attributes
5Term used for materials instead of potency.
Pharmacokinetic property used to exercise medical judgment on suspect drugs.
The highest dose at which no adverse effects are observed (NOAEL).; identified by the subchronic oral study to assess safety
A unique property of biopharmaceuticals affecting animal model selection
Assessment required for therapeutic protein products.
Technical Details
Substances
6Example of cancer immunotherapeutic drugs within scope
Biological activity may necessitate carcinogenicity assessment
Absorption typically less than 1 percent from chronic ulcer sites but may be clinically significant.
including monoclonal antibodies for prophylactic use
Recombinant proteins are produced with recombinant deoxyribonucleic acid technology
Proteins used in preclinical studies when the clinical candidate is not active in species.; Alternative approach for hazard detection
Testing Methods
9Specific consideration for safety evaluation
Nonclinical safety data
Section VII of the guidance.
Used to evaluate comparability based on identity, purity, stability, and potency
Non-animal methods for phototoxicity testing
Used for cross-reactivity studies using a range of human tissues
Data from existing repeated-dose toxicity studies used for dose selection.
Used for quantitation of analytes in animal and human samples
Method for quantitation of radiolabeled proteins
Processes
4Evaluation in targeted areas of the body for combination products.
Used to remove impurities and contaminants
Changes 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
Impaired renal function can alter drug metabolism
Clinical Concepts
5data derived from an assessment of toxicity
The induction of tumors which carcinogenicity testing aims to assess
Assessment of the immune response to the biological product
Study of the biochemical and physiological effects of drugs
Study of how the body interacts with administered substances
Identified Hazards
Hazards
3Risk associated with products from mammalian cells
Warning statement recommended for scented tampons
Unintentional reactivity towards human tissues distinct from the target
Standards & References
Specifications
1Primary goal to identify initial safe dose in humans
ICH References (1)
Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Advanced Manufacturing Technologies Designation Program
- Direct-to-Consumer Prescription Drug Advertisements: Presentation of the Major Statement in a Clear, Conspicuous, and Neutral Manner in Advertisements in Television and Radio Format Final Rule Questions and Answers
- Q4B Annex 8: Sterility Test General Chapter
- Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products: Draft Guidance for Industry
- Interacting with the FDA on Complex Innovative Trial Designs for Drugs and Biological Products: Guidance for Industry
- Failure to Respond to an ANDA Complete Response Letter Within the Regulatory Timeframe Guidance for Industry: Guidance for Industry
- CMC Postapproval Manufacturing Changes for Specified Biological Products To Be Documented in Annual Reports
- Best Practices in Developing Proprietary Names for Human Nonprescription Drug Products; Draft Guidance for Industry: Draft Guidance for Industry