Document ID: FDA-2013-N-1525-0001
Agency: fda
Document Type: Proposed Rule
Title: List of Bulk Drug Substances That May Be Used in Pharmacy Compounding; Bulk Drug Substances That May Be Used To Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act
Posted Date: 2013-12-04T05:00Z

[Federal Register Volume 78, Number 233 (Wednesday, December 4, 2013)]
[Proposed Rules]
[Pages 72841-72843]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-28979]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Chapter I

[Docket No. FDA-2013-N-1525]

List of Bulk Drug Substances That May Be Used in Pharmacy 
Compounding; Bulk Drug Substances That May Be Used To Compound Drug 
Products in Accordance With Section 503A of the Federal Food, Drug, and 
Cosmetic Act

AGENCY: Food and Drug Administration, HHS.

ACTION: Withdrawal of proposed rule; request for nominations.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is 
withdrawing the proposed rule to list bulk drug substances used in 
pharmacy compounding and preparing to develop a list of bulk drug 
substances (bulk drugs) that may be used to compound drug products, 
although they are neither the subject of a United States Pharmacopeia 
(USP) or National Formulary (NF) monograph nor components of FDA-
approved drugs. To identify candidates for this bulk drugs list, 
interested groups and individuals may nominate specific bulk drug 
substances, and FDA is describing the information that should be 
provided to the Agency in support of each nomination.

[[Page 72842]]

DATES: FDA is withdrawing the proposed rule published January 7, 1999 
(64 FR 996), as of December 4, 2013.
    Submit written or electronic nominations for the bulk drug 
substances list by March 4, 2014.

ADDRESSES: You may submit nominations, identified by Docket No. FDA-
2013-N-1525, by any of the following methods.

Electronic Submissions

    Submit electronic nominations in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting ``comments.''

Written Submissions

    Submit written nominations in the following ways:
     Mail/Hand delivery/Courier (for paper submissions): 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name 
and docket number FDA-2013-N-1525 for this request for nominations. All 
nominations received may be posted without change to http://www.regulations.gov, including any personal information provided. For 
additional information on submitting nominations, see the ``Request for 
Nominations'' heading of the SUPPLEMENTARY INFORMATION section of this 
document.
    Docket: For access to the docket to read background documents or 
nominations received, go to http://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.

FOR FURTHER INFORMATION CONTACT: Marissa Chaet Brykman, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, suite 5100, Silver Spring, MD 20993-0002, 
301-796-3110.

SUPPLEMENTARY INFORMATION: 

I. Background

    Section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) 
(21 U.S.C. 353a) describes the conditions under which a human drug 
product compounded for an identified individual patient based on a 
prescription is entitled to an exemption from three sections of the 
FD&C Act: (1) section 501(a)(2)(B) (21 U.S.C. 351(a)(2)(B)) (concerning 
current good manufacturing practice (CGMP) for drugs); (2) section 
502(f)(1) (21 U.S.C. 352(f)(1)) (concerning the labeling of drugs with 
adequate directions for use); and (3) section 505 (21 U.S.C. 355) 
(concerning the approval of human drug products under new drug 
applications (NDAs) or abbreviated new drug applications (ANDAs)).
    One of the conditions for such an exemption is that a drug product 
may be compounded if the licensed pharmacist or licensed physician 
compounds the drug product using bulk drug substances that: ``(I) 
comply with the standards of an applicable United States Pharmacopoeia 
or National Formulary monograph, if a monograph exists, and the United 
States Pharmacopoeia chapter on pharmacy compounding; (II) if such a 
monograph does not exist, are drug substances that are components of 
drugs approved by the Secretary; or (III) if such a monograph does not 
exist and the drug substance is not a component of a drug approved by 
the Secretary, that appear on a list developed by the Secretary through 
regulations issued by the Secretary under subsection (d) [of Section 
503A]'' (section 503A(b)(1)(A)(i) of the FD&C Act).
    Section 503A refers to the definition of ``bulk drug substance'' in 
FDA regulations at 21 CFR 207.3(a)(4): ``any substance that is 
represented for use in a drug and that, when used in the manufacturing, 
processing, or packaging of a drug, becomes an active ingredient or a 
finished dosage form of the drug, but the term does not include 
intermediates used in the synthesis of such substances.'' See section 
503A(b)(1)(A) of the FD&C Act.
    Section 503A(d)(1) of the FD&C Act requires that, before issuing 
regulations to implement section 503A(b)(1)(A)(i)(III) of the FD&C Act, 
an advisory committee on compounding be convened and consulted ``unless 
the Secretary determines that the issuance of such regulations before 
consultation is necessary to protect the public health'' (section 
503A(d)(1) of the FD&C Act).
    As described in more detail below, in 1998, FDA began to develop a 
list of bulk drug substances that may be used in compounding, but 
before a final rule was published, the constitutionality of section 
503A was challenged in court because it included restrictions on the 
advertising or promotion of the compounding of any particular drug, 
class of drug, or type of drug and the solicitation of prescriptions 
for compounded drugs. These provisions were held unconstitutional by 
the U.S. Supreme Court in 2002.\1\ After the court decision, FDA 
suspended its efforts to develop the list of bulk drug substances that 
could be used in compounding.
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    \1\ See Thompson v. Western States Med. Ctr., 535 U.S. 357 
(2002).
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    The Drug Quality and Security Act (DQSA) removes from section 503A 
of the FD&C Act the provisions that had been held unconstitutional by 
the U.S. Supreme Court in 2002.\2\ By removing these provisions, the 
new law removes uncertainty regarding the validity of section 503A, 
clarifying that it applies nationwide. Therefore, FDA is reinitiating 
its efforts to develop a list of bulk drug substances that may be used 
in compounding under section 503A.
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    \2\ The DQSA also adds a new section 503B to the FD&C Act (21 
U.S.C. 353b) that creates a new category of ``outsourcing 
facilities.'' For additional information concerning bulk drug 
substances that may be used to compound drug products in accordance 
with section 503B, see the notice, ``Bulk Drug Substances That May 
Be Used to Compound Drug Products in Accordance with Section 503B of 
the Federal Food, Drug, and Cosmetic Act, Concerning Outsourcing 
Facilities; Request for Nominations'' published in this issue of the 
Federal Register.
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II. Previous Efforts To Develop the List of Bulk Drug Substances Under 
Section 503A of the FD&C Act

    In the Federal Register of April 7, 1998 (63 FR 17011), FDA invited 
all interested persons to nominate bulk drug substances for inclusion 
on the list of bulk drug substances that may be used in compounding 
under section 503A. In total, FDA received nominations for 41 different 
drug substances. After evaluating the nominated drugs and consulting 
with the Pharmacy Compounding Advisory Committee as required by section 
503A, FDA published a proposed rule proposing to list 20 drugs on the 
section 503A bulk drugs list in January 1999 (64 FR 996, January 7, 
1999). The proposed rule also discussed 10 nominated drug substances 
that were still under consideration for the bulk drugs list. The 
Pharmacy Compounding Advisory Committee reconvened in May 1999 to 
discuss drugs included in the proposed rule, in addition to other bulk 
drug substances (see 64 FR 19791 (April 22, 1999)). However, as 
explained previously (see the ``Background'' section), after the 2002 
U.S. Supreme Court decision, the Agency suspended its efforts to 
develop the bulk drugs list under section 503A.
    FDA intends to reconsider the bulk drug substances that were 
proposed for inclusion on the list and that neither have an applicable 
USP or NF monograph nor are components of an FDA-approved drug due to 
the time

[[Page 72843]]

lapse since the last proposal. Therefore, the Agency withdraws the 
proposed rule, ``List of Bulk Drug Substances That May Be Used in 
Pharmacy Compounding,'' published in the Federal Register of January 7, 
1999 (64 FR 996).

III. Request for Nominations

    To identify candidates for this list, FDA is seeking public input 
in the form of specific bulk drug nominations. All interested groups 
and individuals may nominate specific bulk drug substances for 
inclusion on the list. After evaluating the nominations and, as 
required by section 503A, consulting with the USP and the Pharmacy 
Compounding Advisory Committee, FDA will issue the list as a regulation 
under notice-and-comment rulemaking procedures.
    Nominations should include the following information about the bulk 
drug substance being nominated and the product(s) that will be 
compounded using such substance, and any other relevant information 
available. If the information requested is unknown or unavailable, that 
fact should be noted accordingly.

Bulk Drug Substance

     Ingredient name;
     Chemical name;
     Common name(s);
     Chemical grade or description of the strength, quality, 
and purity of the ingredient;
     Information about how the ingredient is supplied (e.g., 
powder, liquid);
     Information about recognition of the substance in foreign 
pharmacopeias and the status of its registration(s) in other countries, 
including whether information has been submitted to USP for 
consideration of monograph development; and
     A bibliography of available safety and efficacy data,\3\ 
including any relevant peer-reviewed medical literature.
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    \3\ FDA recognizes that the available safety and efficacy data 
supporting consideration of a bulk drug substance for inclusion on 
the list may not be of the same type, amount, or quality as is 
required to support an NDA.
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Compounded Product

     Information about the dosage form(s) into which the drug 
substance will be compounded (including formulations);
     Information about the strength(s) of the compounded 
product(s);
     Information about the anticipated route(s) of 
administration of the compounded product(s);
     Information about the past and proposed use(s) of the 
compounded product(s), including the rationale for its use or why the 
compounded product(s), as opposed to an FDA-approved product, is 
necessary; and
     Available stability data for the compounded product(s).
    FDA cannot guarantee that all drugs nominated during the nomination 
period will be considered for inclusion on the next published bulk 
drugs list. Nominations received during the nomination period that are 
supported by the most complete and relevant information will likely be 
evaluated first. Nominations that are not evaluated during this first 
phase will receive consideration for list amendments, as the 
development of this list will be an ongoing process. Individuals and 
organizations also will be able to petition FDA to make additional list 
amendments after the list is published.
    Interested persons may submit either electronic nominations to 
http://www.regulations.gov or written nominations to the Division of 
Dockets Management (see ADDRESSES). It is only necessary to send one 
set of nominations. Identify nominations with the docket number found 
in the brackets in the heading of this document. Received nominations 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

    Dated: November 27, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-28979 Filed 12-2-13; 11:15 am]
BILLING CODE 4160-01-P