Document ID: FDA-2016-D-1267-0035
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Submission for Office of
Management and Budget Review; Comment Request; Guidance for
Industry on Compounded Drug Products That Are Essentially Copies
of an Approved Drug Product Under Section 503B of the Federal Food,
Drug, and Cosmetic Act
Posted Date: 2018-03-28T04:00Z

[Federal Register Volume 83, Number 60 (Wednesday, March 28, 2018)]
[Notices]
[Pages 13286-13288]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-06169]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-1267]

Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Guidance for Industry 
on Compounded Drug Products That Are Essentially Copies of an Approved 
Drug Product Under Section 503B of the Federal Food, Drug, and Cosmetic 
Act

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by April 
27, 2018.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
Fax: 202-395-7285, or emailed to [email protected]. All 
comments should be identified with the OMB control number 0910-NEW and 
title ``Guidance for Industry on Compounded Drug Products That Are 
Essentially Copies of an Approved Drug Product Under Section 503B of 
the Federal Food, Drug, and Cosmetic Act.'' Also include the FDA docket 
number found in brackets in the heading of this document.

[[Page 13287]]

FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-5733, 
[email protected].

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

I. Background

Guidance for Industry on Compounded Drug Products That Are Essentially 
Copies of a Commercially Available Drug Product Under Section 503B of 
the Federal Food, Drug, and Cosmetic Act

OMB Control Number 0910-NEW

    This information collection supports the above captioned Agency 
guidance. Section 503B of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act) (21 U.S.C. 353b) describes conditions that must be met in 
order for compounded drugs to receive exemptions from certain sections 
of the FD&C Act, including section 502(f)(1) (21 U.S.C. 352(f)(1)) 
(concerning the labeling of drugs with adequate directions for use); 
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)) and section 582 (21 U.S.C. 360eee-1) (concerning 
drug supply chain security requirements). One of the conditions that 
must be met for a compounded drug product to qualify for the exemptions 
under section 503B of the FD&C Act is that ``the drug is not 
essentially a copy of one or more approved drugs'' (section 
503B(a)(5)).
    According to section 503B(d)(2) of the FD&C Act, a compounded drug 
is essentially a copy of an approved drug when it (1) is identical or 
nearly identical to an approved drug that is not on FDA's drug shortage 
list at the time the drug is compounded, distributed, and dispensed; or 
to a non-prescription drug product marketed without an approved 
application, or (2) contains the same bulk drug substance as an 
approved drug or a non-prescription drug product marketed without an 
approved application, unless there is a change that produces a clinical 
difference for an individual patient as determined by the prescribing 
practitioner between the compounded drug and the approved drug (see 
section 503B(d)(2)(A) and (B)).
    Under the policy proposed in the draft guidance, if an outsourcing 
facility intends to rely on a prescriber determination made under 
section 503B(d)(2)(B) to establish that a compounded drug is not 
essentially a copy of an approved drug, the outsourcing facility should 
ensure that the determination is documented on the prescription or 
order (which may be a patient-specific prescription or a non-patient 
specific order) for the compounded drug.
    If a prescription or order does not make clear that the 
determination required by section 503B(d)(2)(B) has been made, the 
outsourcing facility may contact the prescriber or health care 
facility, and if the prescriber or health care facility contact 
confirms it, make a notation on the prescription or order that the 
prescriber has determined that the compounded product contains a change 
that produces a clinical difference for patient(s). The date of the 
conversation with the health care facility contact or prescriber, and 
the name of the individual providing the determination, should be 
included on the prescription or order.
    In addition, if the outsourcing facility compounded a drug that is 
identical or nearly identical to an approved drug product that appeared 
on FDA's drug shortage list, the outsourcing facility should maintain 
documentation (e.g., a notation on the order for the compounded drug) 
regarding the status of the drug on FDA's drug shortage list at the 
time of compounding, distribution, and dispensing.
    An outsourcing facility should also maintain records of 
prescriptions or orders including notations that a prescriber has 
determined that the compounded drug has a change that produces a 
clinical difference for an individual patient. Because the time, 
effort, and financial resources necessary to comply with this 
collection of information would be incurred by licensed pharmacists and 
licensed physicians in the normal course of their activities, it is 
excluded from the definition of ``burden'' under 5 CFR 1320.3(b)(2).

II. Paperwork Reduction Act of 1995

    In the Federal Register of July 11, 2016 (81 FR 44879), we 
published a notice of availability for the draft guidance, including an 
analysis of estimated burden under the PRA, and invited public comment 
of the proposed information collection. Several comments were received 
and are discussed below.

III. Comments

    Issue One: Several commenters said it would be unnecessarily 
burdensome for prescribers to document the clinical need for a 
compounded drug, and that a pharmacist, nurse, or other clinician 
choosing to source compounded drugs from an outsourcing facility should 
be able to assess the clinical need for the compounded drug.
    FDA Response to Issue One: Under section 503B(d)(2), if a drug is 
not identical or nearly identical to an approved drug or a covered 
over-the-counter monograph (OTC) drug, and a component of the 
compounded drug is a bulk drug substance that is a component of an 
approved drug or a covered OTC drug, then the drug is essentially a 
copy and may not be compounded under section 503B unless there is a 
change that produces for an individual patient a clinical difference, 
as determined by the prescribing practitioner, between the compounded 
drug and the comparable approved drug. If a prescription or order 
already documents the determination of clinical difference, there is no 
additional documentation burden for the compounder. If a prescription 
or order does not make clear that the determination of clinical 
difference required by the statute has been made, the compounder may 
contact the prescriber, and if the prescriber confirms it, make a 
notation on the prescription or order that the compounded product 
contains a change that makes a clinical difference for the patient. The 
date of the conversation with the health care facility or prescriber, 
and the name of the individual providing the determination, should be 
included on the prescription or order. FDA estimates this contact will 
take 3 minutes and should not present significant burden. Maintaining 
prescription records that may include such notations should not present 
any additional burden, as FDA understands that maintaining records of 
prescriptions or orders for compounded drug products is part of the 
usual course of the practice of compounding and selling drugs.
    FDA also notes that for non-patient specific orders, the guidance 
states that an outsourcing facility may obtain a statement from the 
prescribing practitioner or a person able to make a representation for 
the health care practitioner. For example, a pharmacy manager could 
order a compounded drug and document on the order that the compounded 
drug will only be administered to patients for whom the prescriber 
determines that this formulation will produce a clinical difference.
    Issue Two: At least two commenters raised concerns that 
documentation of the prescriber determination of clinical

[[Page 13288]]

difference could lead to liability concerns (e.g., for a pharmacy 
manager who makes representations to an outsourcing facility about how 
a drug will be used) and scope of practice concerns (if a doctor 
concludes he or she should not be bound by the representations).
    FDA Response to Issue Two: For certain drugs, one of the conditions 
to qualify for exemptions under section 503B is that there is a change 
that produces for an individual patient a clinical difference, as 
determined by the prescribing practitioner, between the compounded drug 
and the comparable approved drug. If a pharmacy manager does not wish 
to document on the order that such a drug will only be administered 
after an appropriate prescriber determination, the manager could ask 
the prescriber to provide documentation. If a prescriber, or person 
able to make a representation for a prescriber, refuses to confirm that 
a compounded drug produces a clinical difference for a patient, the 
compounded drug may be considered ``essentially a copy'' of the 
commercially-available product. The outsourcing facility may decide in 
this scenario to not compound the drug.
    Issue Three: At least one commenter recommended that the guidance 
requires practitioners to provide additional details regarding the 
patient population in need of a compounded drug as part of the 
prescriber determination of clinical difference, and that both a 
hospital and practitioner should produce statements of clinical 
difference.
    FDA Response to Issue Three: FDA's draft guidance states that when 
an outsourcing facility intends to rely on a prescriber determination 
to establish that a compounded drug is not essentially a copy of an 
approved drug, the outsourcing facility should ensure that the 
determination is documented on the prescription or order for the 
compounded drug. This means the determination is referenced in the 
statute at section 503B(d)(2), which FDA cannot change through 
guidance. FDA cannot give exhaustive guidance regarding what such 
documentation may contain, but we did provide appropriate examples. 
Under the guidance, both a prescribing practitioner and a person able 
to make a representation for the practitioner, such as, potentially, a 
hospital pharmacy manager, would be able to produce a statement of 
clinical difference.
    Issue Four: At least one commenter asked about the acceptability of 
specific means of applying a determination statement to a product 
order.
    FDA Response to Issue Four: FDA does not believe a particular 
format is needed for a prescriber determination of clinical difference, 
provided that the determination clearly identifies the relevant change 
made to the compounded product and the clinical difference that the 
change will produce for patient(s), as determined by the prescriber.
    As none of the comments suggested that we revise our estimated 
burden for the information collection, we have retained our original 
estimate as follows:

                                               Table 1--Estimated Annual Third-Party Disclosure Burden \1\
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                                                                  Number of
Type of reporting recommendations in guidance     Number of      disclosures    Total annual         Average burden per disclosure          Total hours
                                                 respondents   per respondent    disclosures
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Consultation between the outsourcing facility              40             100           4,000  0.05 (3 minutes).........................             200
 and prescriber or health care facility, and
 the notation on the prescription or order
 documenting the prescriber's determination
 of clinical difference.
Checking FDA's drug shortage list and                      30             100           3,000  0.03 (2 minutes).........................             100
 documenting on the prescription that the
 drug is in shortage.
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    We estimate that annually a total of approximately 40 outsourcing 
facilities (``number of respondents'' in table 1, line 1) will consult 
a prescriber to determine whether he or she has made a determination 
that the compounded drug has a change that produces a clinical 
difference for an individual patient as compared to the comparable 
approved drug and that outsourcing facilities will document this 
determination on approximately 4,000 prescriptions or orders for 
compounded drugs (``total annual disclosures'' in table 1, line 1). We 
estimate that the consultation between the outsourcing facility and the 
prescriber or health care facility contact adding a notation to each 
prescription or order that does not already document this determination 
will take approximately 3 minutes per prescription or order.
    We estimate that a total of approximately 30 outsourcing facilities 
(``number of respondents'' in table 1, line 2) will document this 
information on approximately 3,000 prescriptions or orders for 
compounded drugs (``total annual disclosures'' in table 1, line 2). We 
estimate that checking FDA's drug shortage list and documenting this 
information will take approximately 2 minutes per prescription or 
order.

    Dated: March 22, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-06169 Filed 3-27-18; 8:45 am]
 BILLING CODE 4164-01-P