Description
This guidance is intended to provide recommendations for study sponsors and/or drug manufacturers, contract research organizations (CROs), site management organizations (SMOs), clinical investigators, and independent third parties regarding the procedure for handling reserve samples from relevant bioavailability (BA) and bioequivalence (BE) studies, as required by 21 CFR 320.38 and 320.63. The guidance highlights (1) how the test article and reference standard for BA and BE studies should be distributed to the testing facilities, (2) how testing facilities should randomly select samples for testing and material to maintain as reserve samples, and (3) how the reserve samples should be retained. The guidance also clarifies and emphasizes points addressed in §§ 320.38 and 320.63.
Scope & Applicability
Product Classes
5topic of the guidance document
Unit containing amount for a single dose, like tablets or capsules
Unit that delivers more than a single dose, such as an ointment tube or inhaler
Products involving drug and device components like injector and vial
Topical systems for which stand-alone adhesion studies may not require reserves
Stakeholders
6Entity submitting development data and knowledge; Entity performing the work process for change
Entity or site not overseen or directed by the applicant or sponsor
Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining
Contract Research Organization responsible for sample retention; Contract Research Organization performing testing under contract
Entity responsible for the study protocol
Entity providing the drug product for testing
Regulatory Context
Attributes
7The standard (RS) used for comparison in studies.; The RS used in BA/BE testing
Specific identified portion of a batch or amount produced in a unit of time
Specific quantity of a drug intended to have uniform character and quality
Study design where treatment assignments are concealed
minimum quantity of 30 single-dose or 3 multi-dose units
The product (T) being tested in studies.; The T product used in BA/BE testing
Samples of T and RS retained for FDA inspection
Related CFR Sections (11)
- 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 →
- 21CFR314.3§ 314.3 Definitions.
(a) The definitions and interpretations contained in section 201 of the Federal Food, Drug, and Cosmetic Act apply to those terms when used in this part and part 320 of this chapter .Read full regulation →
- 21CFR211.170§ 211.170 Reserve samples.
(a) An appropriately identified reserve sample that is representative of each lot in each shipment of each active ingredient shall be retained. The reserve sample consists of at least twice the quantity necessary for all tests required to determine whether the active ingredient meets its establishedRead full regulation →
- 21CFR211.84§ 211.84 Testing and approval or rejection of components, drug product containers, and closures.
(a) Each lot of components, drug product containers, and closures shall be withheld from use until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit.Read 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 →
- 21CFR312.57§ 312.57 Recordkeeping and record retention.
(a) A sponsor shall maintain adequate records showing the receipt, shipment, or other disposition of the investigational drug. These records are required to include, as appropriate, the name of the investigator to whom the drug is shipped, and the date, quantity, and batch or code mark of each such Read full regulation →
- 21CFR314.125§ 314.125 Refusal to approve an NDA.
(a) The Food and Drug Administration will refuse to approve the NDA and for a new drug give the applicant written notice of an opportunity for a hearing under § 314.200 on the question of whether there are grounds for denying approval of the NDA under section 505(d) of the Federal Food, Drug, and CoRead full regulation →
- 21CFR314.127§ 314.127 Refusal to approve an ANDA.
(a) FDA will refuse to approve an ANDA for a new drug under section 505(j) of the Federal Food, Drug, and Cosmetic Act for any of the following reasons, unless the requirement has been waived under § 314.99 :Read full regulation →
- 21CFR314.150§ 314.150 Withdrawal of approval of an application or abbreviated application.
(a) The Food and Drug Administration will notify the applicant, and, if appropriate, all other persons who manufacture or distribute identical, related, or similar drug products as defined in §§ 310.6 and 314.151(a) of this chapter and for a new drug afford an opportunity for a hearing on a proposalRead full regulation →
- 21CFR320.31§ 320.31 Applicability of requirements regarding an “Investigational New Drug Application.”
(a) Any person planning to conduct an in vivo bioavailability or bioequivalence study in humans shall submit an “Investigational New Drug Application” (IND) if:Read full regulation →
- 21CFR10.115§ 10.115 Good guidance practices.
(a) What are good guidance practices? Good guidance practices (GGP's) are FDA's policies and procedures for developing, issuing, and using guidance documents.Read full regulation →
Related Warning Letters (10)
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
SV Labs Corporation
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Guangdong Renhe Guozhuang Biotechnology Co., Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Medinatura New Mexico, Inc.
- 2025-12-16
CGMP/Finished Pharmaceuticals/Adulterated
Sklar Personal Care Inc.
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
- 2025-12-11
CGMP/Finished Pharmaceuticals/Adulterated
Catalent Indiana, LLC
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
DeVere Manufacturing Inc.
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
CDL Services, Inc. DBA Technichem
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
Seaway Pharma Inc.
- 2025-12-02
Compounding Pharmacy/Adulterated Drug Products
PQ Pharmacy, LLC
See Also (8)
- Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action (Status: Draft)
- Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs — General Considerations (Status: Draft)
- ANDAs: Stability Testing of Drug Substances and Products, Questions and Answers (Status: Final)
- 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)
- Data Integrity for In Vivo Bioavailability and Bioequivalence Studies (Status: Draft)
- Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA: Draft Guidance for Industry (Status: Draft)
- Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting: Guidance for Industry (Status: Final)