Description
The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled “Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs—General Considerations” (draft BA and BE guidance for NDAs). The draft guidance provides recommendations to sponsors and/or applicants planning to include bioavailability (BA) and bioequivalence (BE) information for drug products in investigational new drug applications (INDs), new drug applications (NDAs), and NDA supplements. This draft guidance revises those parts of the March 2003 guidance entitled “Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations” relating to BA and BE studies for INDs, NDAs, and NDA supplements.
Scope & Applicability
Product Classes
10Complex dosage forms that may require one batch per strength for evaluation
Use of in vitro data for postapproval changes
Capsules, tablets, and suspensions discussed for in vitro BA/BE
Delayed-release (DR) drug products are dosage forms that release active ingredient at a later time
Extended-release (ER) products are dosage forms designed to extend release
Solubilized dosage forms where BA/BE may be self-evident
Instances where multiple-dose BA studies may be required
Conventional dosage forms; Includes capsules, tablets, and suspensions; data deletion because of vomiting for immediate-release products
Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Scope of products eligible for minor dosage form changes
Stakeholders
3Entity responsible for submitting applications under section 524B
Entity submitting development data and knowledge; Entity performing the work process for change
Possible to conduct the FIH trial in healthy volunteers
Regulatory Context
Attributes
10Drug products with specific variability characteristics
sampling should continue for at least three or more terminal elimination half-lives
area under the concentration-time curve extrapolated to infinity
adequate washout period (e.g., ≥5 half-lives) should separate each treatment
drugs that demonstrate a high intrasubject variability (≥30%)
Similarity factor used to compare dissolution profiles
This guidance defines proportionally similar in the following ways
The amount of product held or processed at a specific step.; Used to calculate servings per batch
For drugs with nonlinear pharmacokinetics over the therapeutic dose range
For drugs with linear pharmacokinetics over the therapeutic dose range
Identified Hazards
Hazards
1potential cause of product failure in sustained-release dosage forms
Related CFR Sections (10)
- 21CFR320.22§ 320.22 Criteria for waiver of evidence of in vivo bioavailability or bioequivalence.
(a) Any person submitting a full or abbreviated new drug application, or a supplemental application proposing any of the changes set forth in § 320.21(c) , may request FDA to waive the requirement for the submission of evidence measuring the in vivo bioavailability or demonstrating the in vivo bioeqRead full regulation →
- 21CFR320.63§ 320.63 Retention of bioequivalence samples.
The applicant of an abbreviated application or a supplemental application submitted under section 505 of the Federal Food, Drug, and Cosmetic Act, or, if bioequivalence testing was performed under contract, the contract research organization shall retain reserve samples of any test article and referRead full regulation →
- 21CFR320.38§ 320.38 Retention of bioavailability samples.
(a) The applicant of an application or supplemental application submitted under section 505 of the Federal Food, Drug, and Cosmetic Act, or, if bioavailability testing was performed under contract, the contract research organization shall retain an appropriately identified reserve sample of the drugRead full regulation →
- 21CFR320.25§ 320.25 Guidelines for the conduct of an in vivo bioavailability study.
(a) Guiding principles.Read full regulation →
- 21CFR320.21§ 320.21 Requirements for submission of bioavailability and bioequivalence data.
(a) Any person submitting a full new drug application to the Food and Drug Administration (FDA) shall include in the application either:Read full regulation →
- 21CFR320.24§ 320.24 Types of evidence to measure bioavailability or establish bioequivalence.
(a) Bioavailability may be measured or bioequivalence may be demonstrated by several in vivo and in vitro methods. FDA may require in vivo or in vitro testing, or both, to measure the bioavailability of a drug product or establish the bioequivalence of specific drug products. Information on bioequivRead full regulation →
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
- 21CFR320.1§ 320.1 Definitions.
The definitions contained in § 314.3 of this chapter apply to those terms when used in this part.Read full regulation →
- 21CFR320.27§ 320.27 Guidelines on the design of a multiple-dose in vivo bioavailability study.
(a) Basic principles.Read full regulation →
- 21CFR320.29§ 320.29 Analytical methods for an in vivo bioavailability or bioequivalence study.
(a) The analytical method used in an in vivo bioavailability or bioequivalence study to measure the concentration of the active drug ingredient or therapeutic moiety, or its active metabolite(s), in body fluids or excretory products, or the method used to measure an acute pharmacological effect shalRead full regulation →
See Also (8)
- Bioavailability Studies Submitted in NDAs or INDs – General Considerations (Status: Final)
- Physicochemical and Structural (Q3) Characterization of Topical Drug Products Submitted in ANDAs (Status: Draft)
- Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action (Status: Draft)
- ANDAs: Stability Testing of Drug Substances and Products, Questions and Answers (Status: Final)
- Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (Status: Draft)
- In Vitro Release Test Studies for Topical Drug Products Submitted in ANDAs (Status: Draft)
- In Vitro Permeation Test Studies for Topical Drug Products Submitted in ANDAs (Status: Draft)
- Handling and Retention of Bioavailability BA and Bioequivalence BE Testing Samples: Draft Guidance for Industry (Status: Draft)