[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