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
| Published date | 08 July 2019 |
| Citation | 84 FR 32268 |
| Record Number | 2019-14355 |
| Section | Rules and Regulations |
| Court | Food And Drug Administration |
Federal Register, Volume 84 Issue 130 (Monday, July 8, 2019)
[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
