[Federal Register Volume 84, Number 130 (Monday, July 8, 2019)]
[Rules and Regulations]
[Pages 32268-32269]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-14355]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 216

[Docket No. FDA-2019-D-2733]


Compliance Policy for Certain Compounding of Oral Oxitriptan (5-
HTP) Drug Products for Patients With Tetrahydrobiopterin (BH4) 
Deficiency; Immediately in Effect Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification of availability.

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SUMMARY: The Food and Drug Administration (FDA, we, or the Agency) is 
announcing the availability of an immediately in effect guidance for 
industry entitled ``Compliance Policy for Certain Compounding of Oral 
Oxitriptan (5-HTP) Drug Products for Patients With Tetrahydrobiopterin 
(BH4) Deficiency.'' This guidance describes FDA's policy concerning the 
conditions under which the Agency does not generally intend to take 
regulatory action against a licensed pharmacist in a State-licensed 
pharmacy or Federal facility or a licensed physician using the bulk 
drug substance oxitriptan (also known as 5-hydroxytryptophan or 5-HTP) 
to compound oral drug products for patients with tetrahydrobiopterin 
(BH4) deficiency. FDA developed this guidance in response to 
communications from pharmacists and caregivers regarding the use of 
oxitriptan to treat patients with BH4 deficiency following issuance of 
a final rule that placed oxitriptan on the list of substances that 
cannot be used to compound drug products in accordance with certain 
compounding provisions of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act).

DATES: The announcement of the guidance is published in the Federal 
Register on July 8, 2019.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time 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): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, 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-2019-D-2733 for ``Compliance Policy With Respect to Certain 
Compounding of Oral Oxitriptan (5-HTP) Drug Products for Patients With 
Tetrahydrobiopterin (BH4) Deficiency.'' 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 Dockets Management Staff 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 Dockets Management Staff. 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: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.

[[Page 32269]]

    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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of the guidance to the 
Office of Communications, Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10001 New 
Hampshire Ave., Hillandale Bldg., 4th Floor, Silver Spring, MD 20993-
0002, 855-543-3784 or 301-796-3400; Fax: 301-431-6353, email: 
[email protected]. Send two self-addressed adhesive labels to assist 
that office in processing your requests. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Tracy Rupp, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 51, Rm. 5171, Silver Spring, MD 20993, 240-402-0260.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of an immediately in effect 
guidance for industry entitled ``Compliance Policy for Certain 
Compounding of Oral Oxitriptan (5-HTP) Drug Products for Patients With 
Tetrahydrobiopterin (BH4) Deficiency.'' This guidance describes FDA's 
policy concerning the conditions under which the Agency does not 
generally intend to take regulatory action against a licensed 
pharmacist in a State-licensed pharmacy or Federal facility or a 
licensed physician using the bulk drug substance oxitriptan to compound 
oral drug products for patients with BH4 deficiency.
    Section 503A of the FD&C Act (21 U.S.C. 353a) describes the 
conditions that must be satisfied for human drug products compounded by 
a licensed pharmacist in a State-licensed pharmacy or Federal facility, 
or by a licensed physician to qualify for exemptions from certain 
requirements of the FD&C Act related to FDA approval prior to 
marketing, current good manufacturing practice requirements, and 
labeling with adequate directions for use (see sections 505, 
501(a)(2)(B), and 502(f)(1) of the FD&C Act (21 U.S.C. 355, 
351(a)(2)(B), and 352(f)(1))). One of the conditions that must be met 
for a compounded drug product to qualify for these exemptions is that a 
licensed pharmacist or licensed physician compounds the drug product 
using bulk drug substances that: (1) Comply with the standards of an 
applicable United States Pharmacopoeia (USP) or National Formulary (NF) 
monograph, if a monograph exists, and the USP chapter on pharmacy 
compounding; (2) if such a monograph does not exist, are drug 
substances that are components of drugs approved by FDA; or (3) if such 
a monograph does not exist and the drug substance is not a component of 
a drug approved by FDA, appear on a list of bulk drug substances 
developed by FDA through regulation. (See section 503A(b)(1)(A)(i) of 
the FD&C Act.)
    On February 19, 2019, FDA issued a final rule (84 FR 4696) 
(``February 19, 2019, final rule''), which established the list of bulk 
drug substances that can be used to compound drug products under 
section 503A of the FD&C Act even though they are not the subject of an 
applicable USP or NF monograph or a component of an FDA approved drug 
product (the 503A Bulks List). (See section 503A(b)(1)(A) of the FD&C 
Act.) The final rule, codified at Sec.  216.23 (21 CFR 216.23), placed 
six bulk drug substances on the 503A Bulks List (Sec.  216.23(a)), and 
identified four others, including oxitriptan, that cannot be used to 
compound drug products under section 503A of the FD&C Act (Sec.  
216.23(b)). Additional bulk drug substances nominated by the public for 
inclusion on this list are currently under consideration and will be 
the subject of future rulemaking.
    FDA developed this guidance in response to communications from 
pharmacists and caregivers regarding the use of oxitriptan to treat 
patients with BH4 deficiency following issuance of the February 19, 
2019, final rule, which placed oxitriptan on the list of bulk drug 
substances that cannot be used to compound drug products under section 
503A of the FD&C Act. According to those communications and other 
information available to the Agency, oxitriptan is the standard of care 
for the treatment of BH4 deficiency, which is caused by several 
different rare enzyme defects that result from gene mutations. BH4 
deficiency is also known as: Primary tetrahydrobiopterin deficiency, 
atypical phenylketonuria (PKU), GTP cyclohydrolase (GTPCH) deficiency, 
6-pyruvoyl-tetrahydropterin synthase (6-PTPS) deficiency, and 
dihydropteridine reductase (DHPR) deficiency. FDA did not consider BH4 
deficiency during its initial review of this substance for the 503A 
Bulks List. Thus, this guidance addresses the conditions under which 
FDA does not intend to take regulatory action against a licensed 
pharmacist in a State-licensed pharmacy or Federal facility or a 
licensed physician for the use of bulk oxitriptan to compound oral drug 
products for the treatment of identified individual patients with BH4 
deficiency provided certain conditions are met. In light of the new 
information regarding use of oral oxitriptan to treat BH4 deficiency, 
FDA is considering whether to reevaluate the exclusion of oxitriptan 
from the 503A Bulks List.
    FDA is issuing this guidance consistent with our good guidance 
practices (GGP) regulation (21 CFR 10.115). We are implementing this 
guidance without prior public comment because we have determined that 
prior public participation is not feasible or appropriate due to the 
public health need for patients with BH4 deficiency to access 
compounded oxitriptan oral drug products (21 CFR 10.115(g)(2)). This 
guidance does not establish any rights for any person and is not 
binding on FDA or the public. Although this guidance is immediately in 
effect, it remains subject to comment in accordance with FDA's GGP 
regulation. This guidance is not subject to Executive Order 12866.

II. Electronic Access

    Persons with access to the internet may obtain the document at 
either https://www.fda.gov/RegulatoryInformation/Guidances/default.htm 
or https://www.regulations.gov. Use the FDA website listed in the 
previous sentence to find the most current version of the guidance.

    Dated: July 1, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-14355 Filed 7-5-19; 8:45 am]
BILLING CODE 4164-01-P