Description
This guidance describes the Center for Drug Evaluation and Research’s (CDER’s) current thinking on appropriate development plans for botanical drugs to be submitted in new drug applications (NDAs) and specific recommendations on submitting investigational new drug applications (INDs) in support of future NDA submissions for botanical drugs. In addition, this guidance provides general information on the over-the-counter (OTC) drug monograph system for botanical drugs. Although this guidance does not intend to provide recommendations specific to botanical drugs to be marketed under biologics license applications (BLAs), many scientific principles described in this guidance may also apply to these products.
Scope & Applicability
Product Classes
4Subject of the guidance document regarding development and regulatory submissions; products that include plant materials, algae, macroscopic fungi, and combinations thereof; Drugs derived from plants, algae, or macroscopic fungi; clinical studies evaluating the botanical drug alone; Heterogeneous nature and uncertainty in defined active constituents.
combinations of two or more active drugs in a single dosage form
Drugs containing cannabis or cannabis-derived compounds; FDA does not recommend relying on published literature for NDA approval of botanical drug products.
Products containing dietary ingredients intended to supplement the diet; The final product category for which the NDI is intended.
Stakeholders
2Entity responsible for submitting applications under section 524B
Entity submitting development data and knowledge; Entity performing the work process for change
Regulatory Context
Attributes
3Evidence required in NDAs to ensure batch-to-batch uniformity; Quality goal for botanical drug products; Ensuring marketing batches have effects consistent with Phase 3 clinical batches.
established based on data from stability studies
A functional role of sodium in food
Related CFR Sections (14)
- 21CFR312.23§ 312.23 IND content and format.
(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an “Investigational New Drug Application” (IND) including, in the following order:Read full regulation →
- 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 →
- 21CFR320.21§ 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 →
- 21CFR25.40§ 25.40 Environmental assessments.
(a) As defined by CEQ in 40 CFR 1508.9 , an EA is a concise public document that serves to provide sufficient evidence and analysis for an agency to determine whether to prepare an EIS or a FONSI. The EA shall include brief discussions of the need for the proposal, of alternatives as required by secRead full regulation →
- 21CFR25.31§ 25.31 Human drugs and biologics.
The classes of actions listed in this section are categorically excluded and, therefore, ordinarily do not require the preparation of an EA or an EIS:Read full regulation →
- 21CFR25.30§ 25.30 General.
The classes of actions listed in this section and §§ 25.31 through 25.35 are categorically excluded and, therefore, ordinarily do not require the preparation of an EA or an EIS:Read full regulation →
- 21CFR299.4§ 299.4 Established names for drugs.
(a) Section 508 of the Federal Food, Drug, and Cosmetic Act (added by the Kefauver-Harris Drug Amendments of 1962; Pub. L. 87-781) authorizes the Commissioner of Food and Drugs to designate an official name for any drug if he determines that such action is necessary or desirable in the interest of uRead 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 →
- 21CFR330.10§ 330.10 Procedures for classifying OTC drugs as generally recognized as safe and effective and not misbranded, and for establishing monographs.
For purposes of classifying over-the-counter (OTC) drugs as drugs generally recognized among qualified experts as safe and effective for use and as not misbranded drugs, the following regulations shall apply:Read full regulation →
- 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 →
- 21CFR314.126§ 314.126 Adequate and well-controlled studies.
(a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been develRead full regulation →
- 21CFR10.30§ 10.30 Citizen petition.
(a) This section applies to any petition submitted by a person (including a person who is not a citizen of the United States) except to the extent that other sections of this chapter apply different requirements to a particular matter.Read full regulation →
- 21CFR330.14§ 330.14 Additional criteria and procedures for classifying OTC drugs as generally recognized as safe and effective and not misbranded.
This section sets forth additional criteria and procedures by which over-the-counter (OTC) drugs initially marketed in the United States after the OTC drug review began in 1972 and OTC drugs without any U.S. marketing experience can be considered in the OTC drug monograph system. This section also aRead full regulation →
- 21CFR312.120§ 312.120 Foreign clinical studies not conducted under an IND.
(a) Acceptance of studies.Read full regulation →
Related Warning Letters (10)
- 2025-12-23
In Vivo Bioavailability-Bioequivalence Studies – Clinical
Maria A. Carballosa, M.D.
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
Celularity, Inc
- 2025-11-18
Nonprescription/OTC
Save Rite Medical
- 2025-11-18
Nonprescription/OTC
Medical Mega
- 2025-11-18
Sponsor/Investigator
Verdure Sciences, Inc.
- 2025-11-18
Nonprescription/OTC
Shoplet
- 2025-09-30
Clinical Investigator (Sponsor)
Pamela K. Den Besten, DDS, MS
- 2025-09-23
Clinical Investigator/Sponsor
Ralph A. DeFronzo, M.D.
- 2025-09-09
Clinical Investigator
Shirish M. Gadgeel, M.D.
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
CCIC Huatongwei International Inspection Co., Ltd.
See Also (8)
- PET Drug Applications - Content and Format for NDAs and ANDAs_2011 (Status: Final)
- Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs — General Considerations (Status: Draft)
- ANDA Submissions — Refuse to Receive for Lack of Justification of Impurity Limits: Guidance for Industry (Status: Final)
- The Use of Physiologically Based Pharmacokinetic Analyses — Biopharmaceutics Applications for Oral Drug Product Development, Manufacturing Changes, and Controls : Draft Guidance for Industry (Status: Draft)
- Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (Status: Draft)
- Bioavailability Studies Submitted in NDAs or INDs – General Considerations (Status: Final)
- Evaluation of Therapeutic Equivalence (Status: Draft)
- Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules (Status: Final)