Description
This guidance is intended to assist manufacturers and clinical investigators involved in the development of therapeutic protein products for human use. In this document, FDA outlines and recommends adoption of a risk-based approach to evaluating and mitigating immune responses to or adverse immunologically related responses associated with therapeutic protein products that affect their safety and efficacy. Any given approach to assessing and mitigating immunogenicity is determined on a case-by-case basis and should take into consideration the risk assessment we describe. For the purposes of this guidance, immunogenicity is defined as the propensity of the therapeutic protein product to generate immune responses to itself and to related proteins or to induce immunologically related adverse clinical events.
Scope & Applicability
Product Classes
6Guidance on immunogenicity assessment and testing
Associated with antibody-mediated pure red cell aplasia in chronic kidney disease patients.
type of drug influencing RSV prophylaxis trial design
Novel structural formats that may create neoantigens
Novel structural formats that may elicit immune responses
Focus of biologics DDI evaluation.
Stakeholders
6Responsible for declaring acceptable market names on labels.
Population group through 12 months of age; Population group for specific labeling rules (through 12 months).
Body that issued a final report on clinical trials.
Entity responsible for submitting applications under section 524B
Source of safety information in clinical trials
Assist sponsors in the nonclinical evaluation
Regulatory Context
Attributes
10Product-specific factor affecting immunogenicity
factor in determining extent of clinical studies
Criteria for diagnosing anaphylaxis in infants, children, and adults.
Determined based on stability data; Established through stability testing; also called dating period.; Established through formal stability studies; Establishing the period during which a drug product is expected to remain within specifications; Period for drug products; The period during which a drug product is expected to remain within specifications; Duration product remains within acceptance criteria; Period during which product remains within specifications; Established for intermediates pu
Specified in the product label based on stability studies
Particles in the 0.1–10 micron range with immunogenic potential
Self-associated protein species that may elicit immune responses
Genetic factors that may predispose patients to undesirable antibody responses.
Modifications imparted to the protein product
Product-specific factor affecting immunogenicity
Identified Hazards
Hazards
9Product-specific factor that can increase immunogenicity
Soluble tungsten causing precipitation of monoclonal antibodies.
Act as an adjuvant for adverse immunogenicity of therapeutic proteins.
Residual tungsten particles may induce protein aggregation
prior knowledge from product development, e.g., on leachables
Impurities that may provoke immune responses
Potential severe allergic reaction that patient history may not predict.
Product-specific factor that can increase immunogenicity
ADA can have severe consequences if it cross-reacts to and inhibits a nonredundant endogenous counterpart.
Related CFR Sections (3)
- 21CFR600.11§ 600.11 Physical establishment, equipment, animals, and care.
(a) Work areas. All rooms and work areas where products are manufactured or stored shall be kept orderly, clean, and free of dirt, dust, vermin and objects not required for manufacturing. Precautions shall be taken to avoid clogging and back-siphonage of drainage systems. Precautions shall be taken Read full regulation →
- 21CFR201.80§ 201.80 Specific requirements on content and format of labeling for human prescription drug and biological products; older drugs not described in § 201.56(b)(1) .
Each section heading listed in § 201.56(d) , if not omitted under § 201.56(d)(3) , shall contain the following information in the following order:Read full regulation →
- 21CFR201.57§ 201.57 Specific requirements on content and format of labeling for human prescription drug and biological products described in § 201.56(b)(1) .
The requirements in this section apply only to prescription drug products described in § 201.56(b)(1) and must be implemented according to the schedule specified in § 201.56(c) , except for the requirement in paragraph (c)(18) of this section to reprint any FDA-approved patient labeling at the end oRead full regulation →
See Also (8)
- Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans: Guidance for Industry (Status: Final)
- Inspection of Injectable Products for Visible Particulates: Draft Guidance for Industry (Status: Draft)
- Labeling for Human Prescription Drug and Biological Products - Implementing the PLR Content and Format Requirements (Status: Final)
- Patient Counseling Information Section of Labeling for Human Prescription Drug and Biological Products — Content and Format (Status: Final)
- Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biological Products — Content and Format Guidance for Industry (Small Entity Compliance Guide) (Status: Final)
- Pediatric Gastroesophageal Reflux Disease: Developing Drugs for Treatment Guidance for Industry (Status: Draft)
- The “Deemed to be a License” Provision of the BPCI Act: Questions and Answers : Guidance for Industry (Status: Final)
- Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biological Products-Content and Format: Draft Guidance for Industry (Status: Draft)