Botanical Drug Development; Guidance for Industry; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice of availability.

SUMMARY:

The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance for industry entitled “Botanical Drug Development.” This guidance describes FDA's current thinking on appropriate development plans for botanical drugs to be submitted in new drug applications (NDAs) and specific recommendations for submitting investigational new drug applications (INDs) to support 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. This guidance replaces the guidance for industry entitled “Botanical Drug Products” issued in June 2004 and finalizes the August 2015 draft guidance entitled “Botanical Drug Development.”

DATES:

Submit either electronic or written comments on Agency guidances at any time.

ADDRESSES:

You may submit comments as follows:

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.
• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

• Mail/Hand delivery/Courier (for written/paper submissions): Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments submitted to the Division of Dockets Management, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2000-D-0103 for “Botanical Drug Development.” Received comments will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

• Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Division of Dockets Management. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

Submit written requests for single copies of this guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT:

Sau L. Lee, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2128, Silver Spring, MD 20993-0002, 301-796-2905.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry entitled “Botanical Drug Development.” This guidance describes the current thinking of the Center for Drug Evaluation and Research (CDER) on appropriate development plans for botanical drugs to be submitted in NDAs and specific recommendations on submitting INDs in support of future NDA submissions for botanical drugs. In addition, this guidance provides general information on the OTC drug monograph system for botanical drugs. Although this guidance does not intend to provide recommendations specific to botanical drugs to be marketed under BLAs, many scientific principles described in this guidance may also apply to these products.

This guidance specifically discusses several areas in which, due to the unique nature of botanical drugs, the Agency finds it appropriate to apply regulatory policies that differ from those applied to nonbotanical drugs, such as synthetic, semi-synthetic, or otherwise highly purified or chemically modified drugs, including antibiotics derived from microorganisms. Because this guidance focuses on considerations unique to botanical drugs, policies and recommendations applicable to both botanical and nonbotanical drugs are generally not covered in this document.

In the Federal Register of August 17, 2015 (80 FR 49240), FDA issued and sought comment on a draft guidance that revised the final guidance for industry “Botanical Drug Products” issued in June 2004. This guidance finalizes the August 2015 draft guidance “Botanical Drug Development” and replaces the June 2004 final guidance. The June 2004 final guidance, August 2015 draft guidance, and related public comments are publicly available in Docket No. FDA-2000-D-0103. The general approach to botanical drug development has remained unchanged since 2004; however, based on improved understanding of botanical drugs and experience acquired in the reviews of NDAs and INDs for these drugs, specific recommendations have been modified and new sections have been added to this guidance to better address late-phase development and NDA submission for botanical drugs. This guidance also addresses the minor comments received from stakeholders on the 2015 draft guidance and provides clarity on the application of the fixed-dose drug combination rule to botanicals.

This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the current thinking of FDA on botanical drug development. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.

II. The Paperwork Reduction Act of 1995

This guidance refers to previously approved collections of information found in FDA regulations. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The guidance explains the circumstances under which FDA regulations require approval of an NDA for marketing a botanical drug product and when such a product may be marketed under an OTC drug monograph. The regulations governing the preparation and submission of an NDA are in part 314 (21 CFR part 314), and the guidance does not contain any recommendations that exceed the requirements of these regulations. FDA has estimated the information collection requirements resulting from the preparation and submission of an NDA, and OMB has approved the burden under OMB control number 0910-0001. FDA anticipates that any NDAs submitted for botanical drug products would be included under the burden estimates approved by OMB for part 314.

The regulations on the procedures for classifying OTC drugs as generally recognized as safe and effective and not misbranded, and for establishing OTC drug monographs, are set forth in § 330.10 (21 CFR 330.10). FDA believes that any botanical drug products that may be eligible for inclusion in an OTC drug monograph under current § 330.10 have already been or are presently being considered for such inclusion.

The guidance also provides scientific and regulatory guidance to sponsors on conducting clinical investigations of botanical drugs. The regulations governing the preparation and submission of INDs are in part 312 (21 CFR part 312). The guidance does not contain any recommendations that exceed the requirements in those regulations. FDA has estimated the information collection requirements resulting from the preparation and submission of an IND under part 312, and OMB has approved the reporting and recordkeeping burden under OMB control number 0910-0014.

III. Electronic Access

Persons with access to the Internet may obtain the guidance at either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or https://www.regulations.gov.