[Federal Register Volume 83, Number 237 (Tuesday, December 11, 2018)]
[Notices]
[Pages 63648-63651]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-26725]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-4087]


The Food and Drug Administration's Proposed Current Good 
Manufacturing Practice Policies for Outsourcing Facilities: 
Considerations Regarding Access to Office Stock; Public Meeting; 
Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public meeting; request for comments.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is 
announcing a public meeting entitled ``FDA's Proposed Current Good 
Manufacturing Practice Policies for Outsourcing Facilities: 
Considerations Regarding Access to Office Stock.'' Stakeholders, 
including healthcare providers (HCPs) and medical specialty groups, 
have expressed concerns regarding the availability of certain 
compounded drug products from outsourcing facilities that they would 
like to have on-hand as in-office supplies of non-patient-specific 
compounded drugs (``office stock''). The purpose of the public meeting 
is to provide HCPs, outsourcing facilities, entities considering 
becoming outsourcing facilities, and other interested parties with an 
opportunity to present to FDA their perspectives concerning access to 
office stock from outsourcing facilities in light of FDA's enforcement 
policies as proposed in the revised draft guidance on current good 
manufacturing practice (CGMP) for human drug compounding outsourcing 
facilities.

DATES: The public meeting will be held on May 21, 2019, from 9 a.m. to 
5 p.m. Submit either electronic or written comments on this public 
meeting by June 21, 2019. See the SUPPLEMENTARY INFORMATION section for 
registration date and information.

ADDRESSES: The public meeting will be held at FDA's White Oak Campus, 
10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great Room 
(Rm. 1503), Silver Spring, MD 20993-0002. Entrance for the public 
meeting participants (non-FDA employees) is through Building 1 where 
routine security check procedures will be performed. For parking and 
security information, please refer to https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    You may submit comments as follows. Please note that late, untimely 
filed comments will not be considered. Electronic comments must be 
submitted on or before June 21, 2019. The https://www.regulations.gov 
electronic filing system will accept comments until 11:59 p.m. Eastern 
Time at the end of June 21, 2019. Comments received by mail/hand 
delivery/courier (for written/paper submissions) will be considered 
timely if they are postmarked or the delivery service acceptance 
receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your 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 comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the 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): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your 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 Docket No. FDA-
2018-N-4087 for ``FDA's Proposed Current Good Manufacturing Practice 
Policies for Outsourcing Facilities: Considerations Regarding Access to 
Office Stock.'' Received comments, those filed in a timely manner (see 
ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' are publicly viewable at 
https://www.regulations.gov or at the Dockets Management Staff between 
9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two

[[Page 63649]]

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 
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 
Dockets Management Staff. 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 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 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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Bronwen Blass, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Silver Spring, MD 20993-0002, 301-796-5092.

SUPPLEMENTARY INFORMATION: 

I. Background

A. Drug Compounding

    Drug compounding is often regarded as the process of combining, 
mixing, or altering ingredients to create a medication tailored to the 
needs of an individual patient. Compounded drug products serve an 
important role for patients whose clinical needs cannot be met by an 
FDA-approved drug product, such as for a patient who has an allergy to 
a certain dye contained in an FDA-approved drug product and needs a 
medication compounded without that dye, or an elderly patient or a 
child who cannot swallow a pill and needs a medicine in a liquid form 
that is not available in an approved product. Drug products can be 
compounded consistent with section 503A of the Federal Food, Drug, and 
Cosmetic Act (FD&C Act) (21 U.S.C. 353a) by licensed pharmacists in 
State-licensed pharmacies and Federal facilities, or by licensed 
physicians, or consistent with section 503B of the FD&C Act (21 U.S.C. 
353b) by compounders known as outsourcing facilities.
    Sometimes, it is necessary for HCPs in hospitals, clinics, offices, 
or other settings to have a certain compounded drug product on hand, so 
they can administer it to a patient who presents with an immediate need 
for the compounded drug product. Such drug products are often known as 
``office stock,'' and outsourcing facilities are uniquely permitted to 
supply these compounded products in accordance with the law.
    For example, if a patient presents at an ophthalmologist's office 
with a fungal eye infection, timely administration of a compounded 
antifungal medication may be critical to preventing vision loss. In 
such a case, the ophthalmologist may need to inject the patient with a 
compounded drug product immediately, rather than writing a prescription 
and waiting for the drug product to be compounded and shipped to the 
prescriber. In other cases, compounded drug products may need to be 
administered by a healthcare practitioner in his or her office because 
it would not be safe for the patient to take the drug home for self-
administration, and it would be preferable for the physician to have 
the drug in his or her office to administer immediately upon diagnosis, 
rather than asking the physician to order the drug and have the patient 
return to the healthcare practitioner for administration.
    Although compounded drugs can serve an important role for certain 
patients in cases such as these, they also can pose a higher risk to 
patients than FDA-approved drugs. Compounded drug products are not FDA-
approved, which means they have not undergone FDA premarket review for 
safety, effectiveness, and quality. Because compounded drug products 
are subject to a lower regulatory standard than FDA-approved drug 
products, they present a greater risk to patients and should not be 
administered to patients unless their medical needs cannot be met by 
FDA-approved drug products.

B. Compounding Under the FD&C Act

    Sections 503A and 503B of the FD&C Act address human drug 
compounding. Section 503A, added to the FD&C Act by the Food and Drug 
Administration Modernization Act of 1997 (Pub. L. 105-115), describes 
the conditions that must be satisfied for human drug products 
compounded by a licensed pharmacist in a State-licensed pharmacy or 
Federal facility, or by a licensed physician, to be exempt from the 
following three sections of the FD&C Act:
     Section 501(a)(2)(B) (21 U.S.C. 351(a)(2)(B)) (concerning 
CGMP requirements);
     section 502(f)(1) (21 U.S.C. 352(f)(1)) (concerning the 
labeling of drugs with adequate directions for use); and
     section 505 (21 U.S.C. 355) (concerning the approval of 
drugs under new drug applications or abbreviated new drug 
applications).
    A compounded drug product may be eligible for the exemptions under 
section 503A of the FD&C Act only if it is, among other things, 
compounded for an identified individual patient based on the receipt of 
a valid prescription order or a notation, approved by the prescribing 
practitioner, on the prescription order that a compounded product is 
necessary for the identified patient. Among other conditions, to 
qualify for the exemptions under section 503A, the drug product must be 
compounded by a licensed pharmacist in a State-licensed pharmacy or a 
Federal facility, or by a licensed physician (section 503A(a)).
    New section 503B, added to the FD&C Act by the Drug Quality and 
Security Act in 2013, created a new category of compounders called 
outsourcing facilities. Section 503B defines outsourcing facility, in 
part, as a facility that is engaged in the compounding of sterile drugs 
(section 503B(d)(4)(A)(i)). An outsourcing facility may engage in 
nonsterile compounding provided that it also engages in the compounding 
of sterile drugs, and provided that it compounds all of its drugs (both 
sterile and nonsterile) in accordance with the conditions of section 
503B.
    Section 503B of the FD&C Act describes the conditions that must be 
satisfied for human drug products 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:
     Section 502(f)(1);
     section 505; and
     section 582 (21 U.S.C. 360eee-1) (concerning drug supply 
chain security requirements).
    In contrast to compounders compounding in accordance with section 
503A of the FD&C Act, outsourcing facilities may, but need not, obtain 
prescriptions for identified individual patients for their

[[Page 63650]]

compounded drug products (section 503B(d)(4)(C)). Outsourcing 
facilities are subject to CGMP requirements in section 501(a)(2)(B). 
They must also be inspected by FDA according to a risk-based schedule 
and are subject to specific adverse event reporting requirements and 
other conditions that help to mitigate the risks of the drug products 
they compound.

C. CGMP Requirements for Outsourcing Facilities

    Elsewhere in this issue of the Federal Register, FDA announced the 
availability of a revised draft guidance for industry entitled 
``Current Good Manufacturing Practice--Guidance for Human Drug 
Compounding Outsourcing Facilities Under Section 503B of the FD&C 
Act.'' (revised draft guidance). FDA previously issued a draft guidance 
for industry on this subject in July 2014 (79 FR 37743). This guidance, 
once final, will provide for conditions under which FDA generally does 
not intend to take regulatory action against an outsourcing facility 
regarding certain CGMP requirements in 21 CFR parts 210 and 211 during 
the interim period before FDA issues regulations specific to 
outsourcing facilities. In developing policies pertaining to CGMP 
requirements for outsourcing facilities, FDA seeks to recognize the 
differences between outsourcing facilities and conventional drug 
manufacturers and to develop policies that reflect the specific 
compounding operations conducted by outsourcing facilities. The revised 
draft guidance proposes a risk-based approach to enforcement of CGMP 
requirements, tailored to the size and scope of outsourcing facilities' 
operations. The policies are aimed at making it more feasible for 
entities to register as outsourcing facilities to compound drugs for 
office stock in accordance with CGMP requirements, while maintaining 
the minimum standards necessary to protect patients from the risks of 
contaminated or otherwise substandard drug products.
    In the revised draft guidance, FDA made a number of revisions to 
address comments submitted on the 2014 draft. For example, the revised 
draft guidance differentiates between CGMP requirements applicable to 
sterile drug products and nonsterile drug products where appropriate. 
Among other changes, FDA made revisions to address comments on (1) 
stability testing, including the assignment of a beyond use date (BUD) 
as an expiration date; (2) a clear definition of ``in-use time,'' 
distinguishing it from ``BUD'' and ``expiration date''; (3) testing 
batches before release for distribution; and (4) collection and use of 
samples retained from distributed batches, known as reserve samples. 
For a more comprehensive discussion of the policies proposed in the 
revised draft guidance, please see the revised draft guidance 
(available at: https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov) and associated notice of availability, 
which FDA is publishing elsewhere in this issue of the Federal 
Register. In the docket for the revised draft guidance, FDA is seeking 
comment on whether the conditions outlined appropriately balance the 
risks and needs associated with compounded drugs produced for office 
stock.

II. Topics for Discussion at the Public Meeting

    FDA is seeking public input regarding outsourcing facilities 
supplying compounded drugs for office stock in light of the CGMP 
policies described in the revised draft guidance, if finalized as 
written. FDA has developed a list of topics to facilitate a productive 
discussion at the public meeting. This list is not intended to be 
exhaustive, and FDA encourages comments on the potential implications 
of the policies pertaining to compliance with CGMP requirements 
described in the revised draft CGMP guidance, if finalized as written, 
for outsourcing facilities supplying drugs compounded for office stock. 
Policies include, but are not limited to, those related to stability 
studies, beyond use dating, and release testing. Issues that are of 
specific interest to the Agency include the following:
     Perspectives related to demand and supply of office stock, 
including:
    [cir] Ways in which HCPs seek to identify outsourcing facilities 
that compound the drugs they want for office stock, as well as issues, 
if any, with this process.
    [cir] Communications between HCPs and outsourcing facilities to 
address potential issues related to requested formulations, timing, and 
order size.
    [cir] Coordination or consolidation of orders among providers for 
same or similar compounded drug products.
    [cir] HCPs' experiences with the availability of office stock 
products from outsourcing facilities.
     Perspectives related to orders for drug products that an 
outsourcing facility has not made or does not routinely make.
    [cir] Factors outsourcing facilities consider before deciding 
whether to fill an order for a requested compounded drug product that 
it has not previously made or does not routinely make.
    [cir] The impact that FDA's policies proposed in the revised draft 
guidance would have on outsourcing facilities filling orders for 
requested products not previously or routinely made.
     Perspectives related to small volume orders of office 
stock products, including:
    [cir] HCPs' experiences seeking small volume orders from 
outsourcing facilities.
    [cir] Factors outsourcing facilities consider before determining 
whether to produce small batches of compounded drug products for office 
stock.
    [cir] The impact that FDA's policies proposed in the revised draft 
guidance would have on outsourcing facilities' decisions regarding 
filling small volume orders and/or producing small batches of 
compounded drug products for office stock.
    [cir] Whether/how the revisions proposed in the revised draft 
guidance would affect registration of compounders engaged in smaller-
scale production as outsourcing facilities.
     Perspectives related to beyond use dating for office stock 
products, including:
    [cir] How long HCPs seek to keep office stock drug products before 
use.
    [cir] The impact that FDA's policies proposed in the revised draft 
guidance would have on outsourcing facilities' production of compounded 
drug products for office stock with beyond use dating desired by HCPs.
    FDA will post the agenda and other meeting materials at least 5 
days before the meeting on the public meeting website. More information 
regarding the meeting, including the public meeting website address, 
will be posted at: https://www.fda.gov/Drugs/NewsEvents/ucm132703.htm.

III. Participating in the Public Meeting

    Registration: Persons interested in attending this public meeting 
must register online by May 7, 2019. Please provide complete contact 
information for each attendee, including name, title, affiliation, 
address, email, and telephone. More information regarding the meeting, 
including the public meeting website address and registration 
instructions, will be posted at: https://www.fda.gov/Drugs/NewsEvents/ucm132703.htm.
    Registration is free and in-person attendance is based on space 
availability, with priority given to early registrants. Early 
registration is recommended because seating is limited; therefore, FDA 
may limit the number of participants from each

[[Page 63651]]

organization. Registrants will receive confirmation when they have been 
accepted. If time and space permit, onsite registration on the day of 
the public meeting will be provided beginning at 8:30 a.m. We will post 
information at https://www.fda.gov/Drugs/NewsEvents/ucm132703.htm if 
registration closes before the day of the public meeting.
    If you need special accommodations due to a disability, please 
contact [email protected] no later than May 14, 
2019.
    Requests for Oral Presentations: During online registration you may 
indicate if you wish to present during a public comment session and 
which topic(s) you wish to address. All requests to make oral 
presentations must be received by March 1, 2019. You will also be asked 
to send [email protected] a brief summary your 
comments by March 1, 2019. Individuals and organizations with common 
interests are urged to consolidate or coordinate their presentations, 
and request time for a joint presentation, or submit requests for 
designated representatives to present. For more information on oral 
presentation requests, visit https://www.fda.gov/Drugs/NewsEvents/ucm132703.htm. Following the close of registration, we will determine 
the amount of time allotted to each presenter and the approximate time 
each oral presentation is to begin. We will do our best to accommodate 
all stakeholders who wish to speak; however, the duration of comments 
may be limited by time constraints, including time allowances for each 
topic. Presenters will be notified of their selection no later than May 
7, 2019. If selected for presentation, any presentation materials must 
be emailed to the [email protected] no later than 
May 14, 2019. No commercial or promotional material will be permitted 
to be presented or distributed at the public meeting.
    Streaming Webcast of the Public Meeting: This public meeting will 
also be webcast. Further information regarding the webcast, including 
the address for the webcast, will be made available at least 2 days in 
advance of the meeting on the public meeting website. More information 
regarding the meeting, including the public meeting website address, 
will be posted at: https://www.fda.gov/Drugs/NewsEvents/ucm132703.htm. 
FDA has verified the website addresses in this document, as of the date 
this document publishes in the Federal Register, but websites are 
subject to change over time.

    Dated: December 4, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-26725 Filed 12-10-18; 8:45 am]
 BILLING CODE 4164-01-P