Federal Register, Volume 78 Issue 233 (Wednesday, December 4, 2013)

[Federal Register Volume 78, Number 233 (Wednesday, December 4, 2013)]
[Proposed Rules]
[Pages 72840-72841]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-28980]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Chapter I

[Docket No. FDA-2013-N-1523]

Drug Products That Present Demonstrable Difficulties for
Compounding Under Sections 503A and 503B of the Federal Food, Drug, and
Cosmetic Act; Request for Nominations

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification; request for nominations.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is preparing
to develop a list of drug products that present demonstrable
difficulties for compounding (difficult-to-compound list). To identify
candidates for this list, FDA is encouraging interested groups and
individuals to nominate specific drug products or categories of drug
products and is describing the information that should be provided to
the Agency in support of each nomination.

DATES: Submit written or electronic comments by March 4, 2014.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2013-
N-1523, by any of the following methods.

Electronic Submissions

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

Written Submissions

Submit written submissions 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 No. FDA-2013-N-1523 for this request for nominations. All
comments received may be posted without change to http://www.regulations.gov, including any personal information provided. For
additional information on submitting comments, 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
comments 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 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 the compounded
drug product is not a ``drug product identified by the Secretary by
regulation as a drug product that presents demonstrable difficulties
for compounding that reasonably demonstrate an adverse effect on the
safety or effectiveness of that drug product'' (section 503A(b)(3)(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)(3)(A) 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).
At a meeting on July 13 and 14, 2000, the Pharmacy Compounding
Advisory Committee discussed and provided FDA with advice about the
Agency's efforts to develop a list of drugs that present demonstrable
difficulties for compounding. FDA had published a notice of that
meeting in the Federal Register of June 29, 2000 (65 FR 40104).
However, before a list could be developed, 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 difficult-to-
compound list.
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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. 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 drug products that present
demonstrable difficulties for compounding that reasonably demonstrate
an adverse effect on the safety or effectiveness of that drug product.
In addition, the DQSA adds a new section 503B to the FD&C Act (21
U.S.C. 353b) that creates a new category of ``outsourcing facilities.''
Outsourcing facilities, as defined in section 503B, are facilities that
meet certain conditions described in section 503B, including
registering with FDA as an outsourcing facility. If these conditions
are satisfied, a drug compounded by or under the direct supervision of
a licensed pharmacist in an outsourcing facility is exempt from two
sections of the FD&C Act: (1) Section 502(f)(1) and (2) section 505;
but not section 501(a)(2)(B).
One of the conditions in section 503B that must be satisfied to
qualify for the exemptions is that an outsourcing facility does not
compound a drug identified (directly or as part of a category of drugs)
on a list published by the Secretary of drugs or categories of drugs
that present demonstrable difficulties for compounding that are
reasonably likely to lead to an adverse effect on the safety or
effectiveness of the drug or category of drugs, taking into account the
risks and benefits to patients, or the drug is compounded in

[[Page 72841]]

accordance with all applicable conditions that are necessary to prevent
the drug or category of drugs from presenting such demonstrable
difficulties (see section 503B(a)(6)(A) and (a)(6)(B) of the FD&C Act).
Section 503B(c)(2) of the FD&C Act requires that before issuing
regulations to implement section 503B(a)(6) of the FD&C Act, an
advisory committee on compounding be convened and consulted.
FDA intends to develop and publish a single list of drug products
and categories of drug products that cannot be compounded and still
qualify for any of the exemptions set forth in sections 503A and 503B
because they present demonstrable difficulties for compounding.

II. Request for Nominations

To identify candidates for the difficult-to-compound list, FDA is
seeking public input in the form of specific drug products or
categories of drug products that are difficult to compound. Interested
groups and individuals may nominate drug products or categories of drug
products that are difficult to compound for inclusion on the list.
After evaluating the nominations and, as required by Congress,
consulting with the Pharmacy Compounding Advisory Committee (see
sections 503A(d)(1) and 503B(c)(2) of the FD&C Act), FDA will issue the
list as a regulation under notice-and-comment rulemaking procedures.
Nominations should include the following for each drug product or
drug product category nominated, and any other relevant additional
information available:
Name of drug product or drug product category;
Reason why the drug product or drug product category
should be included on the list, taking into account the risks and
benefits to patients.
Reasons may include but are not limited to:
[cir] The potential effect of compounding on the potency, purity,
and quality of a drug product, which could affect the safety and
effectiveness of the drug product. Factors that may be relevant to this
determination include:
1. Drug Delivery System
Is a sophisticated drug delivery system required to ensure
dosing accuracy and/or reproducibility?
Is the safety or efficacy of the product a concern if
there is product-to-product variability?
2. Drug Formulation and Consistency
Is a sophisticated formulation of the drug product
required to ensure dosing accuracy and/or reproducibility?
Because of the sophisticated formulation, is product-to-
product uniformity of the drug product often difficult to achieve?
Is the safety or efficacy of the product a concern if
there is product-to-product variability?
3. Bioavailability
Is it difficult to achieve and maintain a uniformly
bioavailable dosage form?
Is the safety or effectiveness of the product a concern if
the bioavailability varies?
4. Complexity of Compounding
Is the compounding of the drug product complex?
Are there multiple, complicated, or interrelated steps?
Is there a significant potential for error in one or more
of the steps that could affect drug safety or effectiveness?
5. Facilities and Equipment
Are sophisticated facilities and/or equipment required to
ensure proper compounding of the drug product?
Is there a significant potential for error in the use of
the facilities or equipment that could affect drug safety or
effectiveness?
6. Training
Is specialized, highly technical training essential to
ensure proper compounding of the drug product?
7. Testing and Quality Assurance
Is sophisticated, difficult-to-perform testing of the
compounded drug product required to ensure potency, purity, performance
characteristics, or other important characteristics prior to
dispensing?
Is there a significant potential for harm if the product
is compounded without proper quality assurance procedures and end-
product testing?
[cir] Adverse effects that could result when the drug product or
drug product category is not made according to appropriate conditions.
FDA cannot guarantee that all drug products or drug product
categories nominated during the nomination period will be considered
for inclusion on the next published difficult to compound list.
Nominations received during the comment 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, because 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 comments regarding
this document to http://www.regulations.gov or written comments to the
Division of Dockets Management (see ADDRESSES). It is only necessary to
send one set comments. Identify comments with the docket number found
in the brackets in the heading of this document. Received comments 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. 2013-28980 Filed 12-2-13; 11:15 am]
BILLING CODE 4160-01-P