
[Federal Register Volume 82, Number 144 (Friday, July 28, 2017)]
[Notices]
[Pages 35214-35216]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-15900]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-2562]


Drug Products That Present Demonstrable Difficulties for 
Compounding Under the Federal Food, Drug, and Cosmetic Act; 
Establishment of a Public Docket

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; establishment of public docket.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is developing 
a list of drug products and categories of drug products that present 
demonstrable difficulties for compounding (the Difficult to Compound 
List). The Agency previously solicited nominations for this list and 
received approximately 71 unique nominations. FDA is establishing a new 
public docket so that interested parties can nominate drug products or 
categories of drug products that were not previously nominated for 
inclusion on the Difficult to Compound List, resubmit previous 
nominations with additional supporting information, or submit comments.

DATES: Nominations for the Difficult to Compound List and comments may 
be submitted to this docket at any time.

ADDRESSES: You may submit nominations or comments as follows:

Electronic Submissions

    Submit electronic nominations or comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting nominations or comments. 
Nominations or comments submitted electronically, including 
attachments, to https://www.regulations.gov will be posted to the 
docket unchanged. Because your nomination or comment will be made 
public, you are solely responsible for ensuring that your nomination or 
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 nomination or comments, that 
information will be posted on https://www.regulations.gov.
     If you want to submit a nomination or comment with 
confidential information that you do not wish to be made available to 
the public, submit the nomination or 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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper nominations or comments submitted to the 
Division of Dockets Management, FDA will post your nomination or 
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. 
[Docket No. FDA-2017-N-2562] for ``Drug Products That Present 
Demonstrable Difficulties for Compounding Under Sections 503A and 503B 
of the Federal Food, Drug, and Cosmetic Act; Establishment of a Public 
Docket.'' Received nominations and 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 Division of 
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a nomination or 
comment with confidential information that you do not wish to be made 
publicly available, submit your nomination or 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 nominations or 
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 
Division of Dockets Management. 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 nomination 
or 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.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper nominations and 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 Division of Dockets Management, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Pawanprit Singh, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 5206, Silver Spring, MD 20993-0002, 240-
402-8866.

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 qualifies for 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 or 
abbreviated new drug applications). One of the conditions for these 
exemptions 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(c)(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

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regulations before consultation is necessary to protect the public 
health.''
    Section 503B of the FD&C Act (21 U.S.C. 353b) describes the 
conditions that must be met for human drugs compounded by or under the 
direct supervision of a licensed pharmacist in an outsourcing facility 
to qualify for exemptions from three sections of the FD&C Act: (1) 
Section 502(f)(1) (21 U.S.C. 352(f)(1)); (2) section 505 (21 U.S.C. 
355); and section 582 (21 U.S.C. 360eee-1) (concerning drug supply 
chain security requirements). Section 503B does not provide an 
exemption from section 501(a)(2)(B).
    One of the conditions in section 503B that must be satisfied for a 
compounded drug to qualify for the exemptions in that section is that 
the drug either (1) is not 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 (2) is compounded 
in accordance with all applicable conditions identified on the list as 
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.
    At a meeting on July 13 and 14, 2000, an advisory committee on 
compounding (specifically, the Pharmacy Compounding Advisory Committee 
(PCAC)) discussed and provided FDA with advice about the Agency's 
efforts to develop a list of drugs that present demonstrable 
difficulties for compounding under section 503A of the FD&C Act. FDA 
published a notice of that meeting in the Federal Register on June 29, 
2000 (65 FR 40104). In the Federal Register of December 4, 2013 (78 FR 
72840), FDA invited all interested persons to nominate drug products or 
categories of drug products for inclusion on the Difficult to Compound 
List. Nominators were asked to include the name of the drug product or 
category of drug products being nominated, as well as the reason the 
drug product or category of drug products should be included on the 
list, taking into account the risks and benefits to patients. The 
notice also included a list of factors that may be relevant to 
determining whether or not a drug product or category of drug products 
should or should not be included on the Difficult to Compound List. 
Approximately 71 unique drug products or categories of drug products 
were nominated for this list.
    On June 18, 2015, the PCAC reviewed and discussed FDA's proposed 
criteria for evaluating whether drug products or categories of drug 
products are demonstrably difficult to compound under sections 503A and 
503B of the FD&C Act. After considering the PCAC's discussion, FDA 
refined the criteria and presented the changes to the PCAC on March 9, 
2016. The six criteria presented to the PCAC for evaluating whether a 
drug product or category of drug products is demonstrably difficult to 
compound are the following: (1) The complexity of the formulation; (2) 
the complexity of the drug delivery mechanism; (3) the complexity of 
the dosage form; (4) the complexity of achieving bioavailability; (5) 
the complexity of the compounding process; and (6) the complexity of 
physicochemical or analytical testing. Additional information regarding 
these criteria can be found in the briefing package for the March 2016 
PCAC meeting. See http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/UCM486146.pdf.

II. Establishment of a Public Docket

    FDA is establishing a public docket so that interested parties can 
nominate drug products or categories of drug products for inclusion on 
the Difficult to Compound List, resubmit previous nominations with 
additional supporting information, or submit comments.
    Nominations should include the following two items for each drug 
product or category of drug products nominated, and any other relevant 
additional information available:
     The name of the drug product or drug product category;
     The reason the drug product or drug product category 
should be included on the list, taking into account any risks and 
benefits to patients.
    To facilitate FDA's review, nominations may include responses to 
the following six questions, which are related to the criteria FDA 
presented to the PCAC for evaluating whether drug products and 
categories of drug products are difficult to compound under sections 
503A and 503B of the FD&C Act:
    1. Does the drug product or category of drug products have a 
complex formulation that presents a demonstrable difficulty for 
compounding that is reasonably likely to lead to an adverse effect on 
the safety or effectiveness of the drug product?
    2. Does the drug product or category of drug products have a 
complex drug delivery mechanism that presents a demonstrable difficulty 
for compounding that is reasonably likely to lead to an adverse effect 
on the safety or effectiveness of the drug product?
    3. Does the drug product or category of drug products involve a 
complex dosage form that presents a demonstrable difficulty for 
compounding that is reasonably likely to lead to an adverse effect on 
the safety or effectiveness of the drug product?
    4. Does the drug product or category of drug products involve 
complexities in achieving and/or assessing bioavailability that present 
a demonstrable difficulty for compounding that is reasonably likely to 
lead to an adverse effect on the safety or effectiveness of the drug 
product?
    5. Does compounding the drug product or category of drug products 
involve a complex compounding process that presents a demonstrable 
difficulty for compounding that is reasonably likely to lead to an 
adverse effect on the safety or effectiveness of the drug product?
    6. Does compounding the drug product or category of drug products 
necessitate complex physicochemical or analytical testing that presents 
a demonstrable difficulty for compounding that is reasonably likely to 
lead to an adverse effect on the safety or effectiveness of the drug 
product?
    It is not necessary for a previously nominated drug product or 
category of drug products to be renominated to this docket. Previously 
nominated drug products or categories of drug products may be 
renominated to this docket if the nominator wants to provide additional 
supporting information, e.g., information specific to the six questions 
listed above related to FDA's proposed evaluation criteria. Interested 
parties can also submit comments on nominated drug products or 
categories of drug products, or on this document, via this docket.
    Previous nominations to the Difficult to Compound List or comments 
submitted in response to the December 4, 2013 Federal Register notice 
can be viewed on https://www.regulations.gov under docket number FDA-
2013-N-1523, or by going to the Division of Dockets Management between 
9 a.m. and 4 p.m., Monday through Friday.


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    Dated: July 24, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-15900 Filed 7-27-17; 8:45 am]
BILLING CODE 4164-01-P


