[Federal Register Volume 83, Number 175 (Monday, September 10, 2018)]
[Notices]
[Pages 45631-45640]
[FR Doc No: 2018-19461]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-3065]

Memorandum of Understanding Addressing Certain Distributions of
Compounded Drug Products Between the States and the Food and Drug
Administration; Revised Draft; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability; withdrawal.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
announcing the availability for public comment of a revised draft
standard memorandum of understanding (MOU) entitled ``Memorandum of
Understanding Addressing Certain Distributions of Compounded Drug
Products Between the State of [insert State] and the U.S. Food and Drug
Administration'' (revised draft standard MOU). The revised draft
standard MOU describes the responsibilities of a State that chooses to
sign the MOU in investigating and responding to complaints related to
compounded drug products compounded in the State and distributed
outside the State and in addressing the interstate distribution of
inordinate amounts of compounded drug products.
    FDA is also announcing the withdrawal of an earlier draft standard
MOU entitled ``Memorandum of Understanding Addressing Certain
Distributions of Compounded Human Drug Products Between the State of
[insert State] and the U.S. Food and Drug Administration,'' which was
issued in February 2015 (2015 draft standard MOU). The 2015 draft
standard MOU is superseded by the revised draft standard MOU.

DATES: FDA is withdrawing its draft standard MOU that published on
February 19, 2015 (80 FR 8874), as of September 10, 2018. Submit either
electronic or written comments on the revised draft standard MOU by
December 10, 2018, to ensure that the Agency considers your comment on
this draft MOU before it begins work on the final version of the MOU.
Submit either electronic or written comments on information collection
issues under the Paperwork Reduction Act of 1995 by December 10, 2018
(see the ``Paperwork Reduction Act of 1995'' section of this document).

ADDRESSES: You may submit comments on the MOU at any time as follows:

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 the Docket No.
FDA-2018-N-3065 for ``Memorandum of Understanding Addressing Certain
Distributions of Compounded Drug Products Between the States and the
Food and Drug Administration; Revised Draft; Availability.'' Received
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 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 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.
    Submit written requests for single copies of the draft MOU to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-
addressed adhesive label to assist that office in processing your
requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft document.

FOR FURTHER INFORMATION CONTACT: Sara Rothman, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 5197, Silver Spring, MD 20993-0002, 301-
796-3110.

SUPPLEMENTARY INFORMATION:

I. Background

    Section 503A of the Federal Food, Drug, and Cosmetic Act (the FD&C
Act) (21 U.S.C. 353a) describes the conditions that must be satisfied
for drug products compounded by a licensed pharmacist or licensed
physician to be exempt from the following 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 (CGMP) requirements), (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 drugs under new drug applications or abbreviated new
drug applications).
    One of the conditions to qualify for the exemptions listed in
section 503A of the FD&C Act is that: (1) The drug product is
compounded in a State that has entered into an MOU with FDA that
addresses the distribution of inordinate amounts of compounded drug
products interstate and provides for appropriate investigation by a
State agency of complaints relating to drug products distributed
outside such State or (2) if the drug product is compounded in a State
that has not entered into such an MOU, the licensed pharmacist,
pharmacy, or physician does not distribute, or cause to be distributed,
compounded drug products out of the State in which they are compounded
in quantities that exceed 5 percent of the total prescription orders
dispensed or distributed by such pharmacy or physician (5 percent
limit) (see section 503A(b)(3)(B)(i) and (ii) of the FD&C Act).
    Section 503A(b)(3)(B) of the FD&C Act directs FDA to develop, in
consultation with the National Association of Boards of Pharmacy
(NABP), a standard MOU for use by the States in complying with section
503A(b)(3)(B)(i).

II. Previous Efforts To Develop a Standard MOU

    In the Federal Register of January 21, 1999 (64 FR 3301), FDA
announced the availability for public comment of a draft standard MOU,
developed in consultation with NABP (1999 draft standard MOU). Over
6,000 commenters submitted comments on the 1999 draft standard MOU.
Because of litigation over the constitutionality of the advertising,
promotion, and solicitation provision in section 503A of the FD&C
Act,\1\ the draft standard MOU was not completed. In 2013, section 503A
of the FD&C Act was amended by the Drug Quality and Security Act (DQSA)
(Pub. L. 113-54) to remove the advertising, promotion, and solicitation
provisions that were held unconstitutional, and FDA took steps to
implement section 503A, including the provisions on the MOU. In the
Federal Register of February 19, 2015 (80 FR 8874), FDA withdrew the
1999 draft standard MOU and issued the 2015 draft standard MOU for
public comment. FDA received more than 3,000 comments on the 2015 draft
standard MOU. By this notice, FDA is withdrawing the 2015 draft
standard MOU, and the revised draft standard MOU made available today
supersedes the 2015 draft standard MOU.
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    \1\ The conditions of section 503A of the FD&C Act originally
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 challenged in court and held unconstitutional by the
U.S. Supreme Court in 2002. See Thompson v. Western States Med.
Ctr., 535 U.S. 357 (2002).
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III. 503A Guidance

    Immediately after the enactment of the DQSA, in December 2013, the
Agency published a draft guidance on section 503A of the FD&C Act
entitled ``Pharmacy Compounding of Human Drug Products Under Section
503A of the Federal Food, Drug, and Cosmetic Act'' (2013 draft 503A
guidance) (see 78 FR 72901, December 4, 2013) announcing the
availability of the draft guidance). The 2013 draft 503A guidance
described FDA's proposed policy with regard to specific provisions of
section 503A of the FD&C Act that require rulemaking or other action by
FDA, such as the MOU provisions. Several commenters on the 2013 draft
503A guidance offered FDA their views on the MOU provisions of section
503A of the FD&C Act. FDA considered these comments in developing the
2015 draft standard MOU and the revised draft standard MOU it is
issuing today. The final 503A guidance (available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm469119.pdf), published July 2, 2014 (see 79 FR 37742
announcing the availability of the final 503A guidance), states that
FDA does not intend to enforce the 5 percent limit on distribution of
compounded drug products out of the State in which they are compounded
until after FDA has finalized an MOU and made it available to the
States for their consideration and signature. After considering any
comments on the revised draft standard MOU submitted to this docket,
FDA intends to finalize the MOU and make it available for signature by
individual States. FDA will determine at the time of publication of the
final MOU how long it will allow States to consider whether to sign the
MOU before FDA begins to enforce the 5 percent limit in those States
that have not signed an MOU. As discussed below, FDA is proposing a
180-day period.

IV. Revised Draft Standard MOU

    FDA has now developed a revised draft standard MOU on which it is
soliciting public comment. FDA has consulted with NABP in developing
this revised draft standard MOU. FDA also considered the comments
submitted on the 2015 draft standard MOU, as well as comments on the
MOU provisions it received in connection with the 2013 draft 503A
guidance. Below, FDA has summarized and discussed key provisions of the
revised draft standard MOU and, where appropriate, summarized changes
that the Agency made in the revised draft standard MOU. Drug products
intended for veterinary use, repackaged drug products, biological
products subject to licensure through a biologics license application
under section 351 of the Public Health Service Act (42 U.S.C. 262), and
drug products compounded by outsourcing facilities are not the subject
of the revised draft standard MOU.

A. Investigation of Complaints

    The revised draft standard MOU provides that States that enter into
the MOU will agree to:
     Investigate complaints relating to drug products
compounded by a pharmacist in the State and distributed outside the
State by a pharmacy, including complaints about adverse drug
experiences or product quality issues to, among other things, take
steps to assess whether there is a public health risk and whether such
risk is adequately contained;
     Take action, in accordance with and as permitted by State
law, to ensure that the relevant compounding pharmacy investigates the
root cause of the problem and addresses any public health risk
identified in relation to the complaint;
     Notify FDA as soon as possible, but no later than 3
business days, after receiving any complaints relating to a drug
product compounded by a pharmacist in the State and distributed outside
the State involving a serious adverse drug experience or serious

product quality issue, and provide FDA with certain information about
the complaint, including the following:
    [cir] Name and contact information of the complainant;
    [cir] Name and address of the pharmacy/physician that is the
subject of the complaint;
    [cir] Description of the complaint, including a description of any
compounded drug product that is the subject of the complaint; and
    [cir] State's initial assessment of the validity of the complaint
relating to a compounded drug product distributed outside the State, if
available;
     Subsequent to this notification, provide FDA with the
results (description and date of any State actions) of its
investigation;
     Notify the appropriate regulator of physician compounding
within the State of any complaints about adverse drug experiences or
product quality issues related to drug products compounded by a
physician in the State and distributed outside the State; and
     Maintain records of the complaints it receives, the
investigation of each complaint, and any response to or action taken as
a result of a complaint, beginning when the State receives notice of
the complaint. The revised draft standard MOU says that the State
agrees to maintain these records for at least 3 years, beginning on the
date of final action or the date of a decision that the complaint
requires no action.
    The types of complaints of compounded drug products that should be
investigated include any adverse drug experience and product quality
issues. Even non-serious adverse drug experiences and product quality
issues can be indicative of problems at a compounding facility that
could result in product quality defects leading to serious adverse drug
experiences if not corrected. For example, inflammation around the site
of an injection can indicate drug product contamination from inadequate
sterile practices at the compounding pharmacy. If the pharmacy has
inadequate sterile practices, other more serious contamination could
result in serious adverse events.
    The revised draft standard MOU does not include specific directions
to the States relating to how to conduct their investigation of
complaints. Rather, as recommended by comments submitted to FDA
previously, the details of such investigations are left to the States'
discretion. For example, a State may review an incoming complaint
describing an adverse drug experience and determine that such a
complaint does not warrant further investigation. In other cases, a
State may determine that an incoming complaint contains insufficient
information and investigate further to determine appropriate action.
    States signing the revised draft standard MOU would agree to notify
FDA about certain complaints and provide FDA with certain information
about the complaints so FDA could investigate the complaints itself, or
take other appropriate action.\2\ FDA received comments that it was not
feasible for States to notify FDA of certain complaints within a 72-
hour timeframe, as described in the 2015 draft standard MOU. Comments
noted that gathering the information requested for submissions within
just 72 hours might be difficult for States, particularly given that
this period might overlap with a weekend or holiday. Some comments
requested up to 7 days to provide the notification, but several others
suggested that FDA revise the notification period to 3 business days.
FDA has now revised the MOU to reflect the latter approach. The revise
draft standard MOU provides that notification will occur as soon as
possible, but no later than 3 business days after the State receives
the complaint. This period will continue to facilitate early Federal/
State collaboration on serious adverse drug experiences and serious
product quality issues that have the potential to affect patients in
multiple States, while providing for notification in a time frame that
is more feasible for the States. We note that FDA has staff on call 24
hours a day to receive information in emergency situations.
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    \2\ FDA is currently considering whether to propose regulations
or issue guidance documents to further its implementation of section
503A(b)(3)(B) of the FD&C Act. Notice of any such action will be
provided in the Federal Register.
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    Comments also expressed concern that certain provisions regarding
complaint investigation that States entering into the MOU would agree
to may require States to take action not permitted by State law and may
imply that, after taking action, the State has made a legal
determination that the complaint has been resolved. The revised draft
standard MOU clarifies that the State should investigate and take
action that the State considers to be appropriate with respect to the
complaint in accordance with and as permitted by State law. FDA has
also clarified that, by signing the MOU, the State agrees to assess the
existence of a public health risk associated with the complaint and
whether such risk is adequately contained rather than make definitive
determinations of risk or confirm containment.

B. Inordinate Amounts

    The revised draft standard MOU provides that States that enter into
the MOU will agree to:
     On an annual basis (at minimum), identify, using surveys,
reviews of compounding records during inspections of compounding
pharmacies, or other mechanisms available to the State, compounding
pharmacies that distribute inordinate amounts of compounded drug
products interstate by collecting information regarding the following:
    [cir] Total number of prescription orders for compounded drug
products distributed or dispensed intrastate, and
    [cir] Total number of prescription orders for compounded drug
products distributed interstate;
     If the State becomes aware of a physician who is
distributing compounded drug products interstate, coordinate with the
appropriate regulator of physician compounding within the State to
determine, using surveys, reviews of records during inspections, or
other mechanisms available to the State, whether the physician
distributes inordinate amounts of compounded drug products interstate
by collecting information regarding the following:
    [cir] Total number of prescription orders for compounded drug
products distributed or dispensed intrastate, and
    [cir] Total number of prescription orders for compounded drug
products distributed interstate;
     For pharmacies or physicians that have been identified as
distributing inordinate amounts of compounded drug products interstate,
collect information regarding the following:
    [cir] Total number of prescription orders for sterile compounded
drugs distributed interstate;
    [cir] Number of States in which the compounding pharmacy or
physician is licensed or into which the compounding pharmacy or
physician distributes compounded drug products; and
    [cir] Whether the State inspected for and found during its most
recent inspection that the compounding pharmacy or physician
distributed compounded drug products without valid prescriptions for
individually identified patients;
     Notify FDA if the State identifies any pharmacy or
physician within its jurisdiction that has distributed inordinate
amounts of compounded drug products interstate; and
     Provide FDA with the following information regarding
pharmacies or physicians that distributed inordinate amounts of
compounded drug products interstate:

    [cir] Name and address of the pharmacy/physician;
    [cir] Total number of prescription orders for compounded drug
products distributed or dispensed intrastate;
    [cir] Total number of prescription orders for compounded drug
products distributed interstate;
    [cir] Total number of prescription orders for sterile compounded
drugs distributed interstate,
    [cir] Number of States in which the compounding pharmacy or
physician is licensed or into which it distributes compounded drug
products, and
    [cir] Whether the State inspected for and found during its most
recent inspection that the compounding pharmacy or physician
distributed compounded drug products without valid prescriptions for
individually identified patients.
    In the revised draft standard MOU, a pharmacy or physician is
considered to have distributed an inordinate amount of compounded drug
products interstate if the number of prescription orders for compounded
drug products distributed interstate during any calendar month is
greater than 50 percent of the number of prescription orders for
compounded drug products dispensed or distributed both intrastate and
interstate by such pharmacy or physician during that calendar month.
This concept would be called the 50 percent threshold.
    Section 503A of the FD&C Act reflects Congress' recognition that
compounding may be appropriate when it is based on receiving a valid
prescription or notation from a prescribing practitioner for an
identified individual patient. However, drug products compounded under
section 503A are not required to demonstrate that they are safe or
effective, bear adequate directions for use, or conform to CGMP.
Congress, therefore, imposed strict limits on the distribution of drug
products compounded under section 503A to protect the public health and
the integrity of the drug approval process.
    In particular, Congress did not intend for compounders operating
under these statutory provisions to grow into conventional
manufacturing operations making unapproved drugs, operating a
substantial proportion of their business interstate, without adequate
oversight. Although other provisions of the FD&C Act apply to State-
licensed pharmacies and physicians that may qualify for the exemptions
under section 503A of the FD&C Act (e.g., the adulteration provisions
for making drugs under insanitary conditions), and although FDA may
take action in appropriate cases against compounders that violate these
provisions or that operate outside of the conditions in section 503A,
Congress recognized that these compounders are primarily overseen by
the States. If a substantial proportion of a compounder's drugs are
distributed outside a State's borders, adequate regulation of those
drugs poses significant challenges to State regulators. States face
logistical, regulatory, and financial challenges inspecting compounders
located outside of their jurisdiction. In addition, if a compounder
distributes drugs to multiple States, it can be very difficult to
gather the scattered information about possible adverse events
associated with those drugs, connect them to the compounder, and
undertake coordinated action to address a potentially serious public
health problem.
    Therefore, as a baseline measure, section 503A(b)(3)(B) of the FD&C
Act limits the distribution of compounded drug products outside of the
State in which they are compounded to 5 percent of the total
prescription orders dispensed or distributed by a licensed pharmacist,
pharmacy or physician. It then directs FDA, in consultation with NABP,
to develop a standard MOU that addresses the distribution of inordinate
amounts of compounded drug products interstate and provides for
appropriate investigation by a State agency of complaints relating to
drug products compounded in and distributed outside such State.
Implementation of this provision involves FDA describing what
inordinate amounts means and providing a mechanism for addressing
interstate distribution of inordinate amounts of compounded drug
products, as long as the States agree to appropriately investigate
complaints relating to drug products compounded in and distributed out
of the State.
    In the 2015 draft standard MOU, FDA proposed that distribution
interstate up to a 30 percent limit would not be inordinate, and that
States entering into the MOU would agree to take action regarding
pharmacists, pharmacies, or physicians that distribute inordinate
amounts of compounded drugs interstate. FDA received a number of
comments indicating that certain pharmacies, such as pharmacies located
near state borders and home infusion pharmacies, distribute more than
30 percent of their compounded drugs to patients interstate because,
for example, the patients are located in another nearby State, or
because few pharmacies compound a particular drug to treat an uncommon
condition for patients dispersed throughout the country. The comments
noted that the proposed definition of inordinate amounts and the
proposed provision in which States agree to take action could prevent
such pharmacies from fulfilling patients' medical needs for the drugs
that they supply. Other comments expressed concern about instances in
which pharmacies are located near a State border and distribute
compounded drugs to the other side of that border. FDA also received
general comments questioning the Agency's basis for the 30 percent
limit and indicating that it was too low. Some comments suggested that
FDA increase the limit, including a suggestion to increase it to 50
percent.
    The revised draft standard MOU addresses these comments in two
respects. First, it would remove the provision in the 2015 draft
standard MOU that States agree to take action with respect to the
distribution of inordinate amounts of compounded drug products
interstate. Second, it would change what is considered ``inordinate
amounts'' from a 30 percent limit to a 50 percent threshold.
    With respect to State action, the revised draft standard MOU
instead provides that States entering into the MOU would agree to
inform FDA of compounders that have distributed an inordinate amount of
compounded drug products interstate. The Agency does not intend to take
action against a compounder located in a State that has entered into
the MOU solely because the compounder has exceeded the threshold for
inordinate amounts. Rather, FDA proposes that States collect further
information on compounders that have distributed inordinate amounts
interstate and provide this information to FDA to help inform
inspectional priorities.
    States generally have day-to-day oversight responsibilities over
State-licensed pharmacies, pharmacists, and physicians. In general, FDA
considers a pharmacy or physician that distributes the majority of its
compounded drugs intrastate to be primarily overseen by the State,
which is responsible both for regulation of the compounder and
protection of its citizens who receive the compounded drugs. However,
as discussed above, if a substantial proportion of a compounder's drugs
is distributed outside a State's borders, adequate regulation of those
drugs poses significant challenges to State regulators. In such cases,
although State oversight continues to be critical, additional oversight
by FDA may afford an important public health benefit.
    As stated above, in the revised draft standard MOU, FDA proposes
eliminating the 30 percent limit and instead establishing 50 percent as
the threshold beyond which the amount of compounded drugs distributed

interstate would be considered inordinate. Under this proposal, the
threshold triggers an information collection and reporting obligation
once it is reached. The Agency believes that more than 50 percent is an
appropriate measure of ``inordinate amounts'' because it marks the
point at which pharmacies and physicians are distributing the majority
of their compounded drug products interstate, and the regulatory
challenges associated with interstate distributors discussed above
become more pronounced. At this tipping point, the risk posed by the
distribution practices of the compounder may weigh in favor of
additional Federal oversight in addition to State oversight.
    FDA recognizes that in some cases, compounders may distribute more
than 50 percent of a small quantity of compounded drug products to
contiguous States. Although such compounders have exceeded the
inordinate amounts threshold proposed in the revised draft standard
MOU, FDA would consider other information, such as the number of
patients that will receive the compounded drugs, if available, when
assessing the compounders' priority for risk-based inspection.
Accordingly, when a State identifies a pharmacy or physician that
distributes an inordinate amount of compounded drug products
interstate, the draft standard MOU provides that the State would supply
the Agency with: (1) Information about the total number of prescription
orders for compounded drug products that it distributed or dispensed
intrastate; (2) the total number of prescription orders for compounded
drug products that it distributed interstate; (3) the total number of
prescription orders for sterile compounded drug products that it
distributed interstate; (4) the number of States in which the
compounder is licensed; and (5) whether the State inspected for and
found during its most recent inspection that the compounding pharmacy
or physician distributed compounded drug products without valid
prescriptions for individually identified patients. FDA intends to use
this information to prioritize its inspections of compounders based on
risk, focusing on those that appear likely to distribute large volumes
of compounded drug products, particularly when the distribution is to
multiple States, the drug products are intended to be sterile, and
there is information about a lack of valid prescriptions for
individually identified patients.
    FDA has further revised the calculation of inordinate amounts as
follows. The 2015 draft standard MOU provided that a compounder is
considered to have distributed an inordinate amount of compounded drug
products interstate if the number of units of compounded drug products
distributed interstate during any calendar month is equal to or greater
than 30 percent of the number of units of compounded and non-compounded
drug products distributed or dispensed both intrastate and interstate
by such compounder during that calendar month. FDA received comments
noting that because the calculation includes both compounded and non-
compounded drug products, in many cases, a substantial factor in
whether a compounder has distributed an inordinate amount of compounded
drug products interstate is whether the compounder offers non-
compounded drug products. For example, under that policy, many
specialty compounding pharmacies that engage in interstate distribution
and only distribute compounded drug products would be able to
distribute fewer compounded drug products interstate before reaching an
inordinate amount than a pharmacy that also fills prescriptions for
non-compounded drug products, even if both pharmacies produced the same
amount of compounded drug products. After considering the public
comments, FDA does not believe that including non-compounded drug
products within the calculation of inordinate amounts would help
address the public health concerns associated with sending compounded
drug products out of State that Congress sought to address in section
503A(b)(3)(B) of the FD&C Act. Accordingly, for purposes of the revised
draft standard MOU, FDA is proposing to exclude consideration of non-
compounded drug products from the calculation of inordinate amounts so
that the denominator is determined by solely referencing compounded
drug products.\3\
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    \3\ FDA also intends to exclude non-compounded drugs from the
calculation of the 5 percent limit in section 503A(b)(3)(B)(ii).
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C. Definitions

    Appendix A in the revised draft standard MOU defines key terms used
in the MOU. FDA is retaining the definitions of ``adverse drug
experience,'' ``serious adverse drug experience,'' ``product quality
issue,'' and ``serious product quality issue'' from the 2015 draft
standard MOU.
    The revised draft standard MOU also defines ``distribution.'' With
respect to that definition, for purposes of the revised draft standard
MOU, FDA proposes that distribution means that a compounder has sent a
compounded drug product out of the facility in which the drug was
compounded. Such distribution may include, but is not limited to,
delivery or shipment to a physician's office, hospital, or other health
care setting for administration, and dispensing the drug product by
sending it to a patient for the patient's own use. This definition is
revised from the 2015 draft standard MOU and is intended to address
stakeholder comments and to better effectuate the purposes of section
503A of the FD&C Act.
    In the 2015 draft standard MOU, FDA proposed to define the term
``distribution'' to include, among other things, dispensing of a
compounded drug product to a patient for the patient's own use. We
received a number of comments on the 2015 draft standard MOU stating
that distributing and dispensing are mutually exclusive activities,
such that if a drug product is distributed, it is not also dispensed,
and vice versa. Some comments asserted, in particular, that a
compounded drug product should not be considered to be ``distributed''
when it is provided pursuant to a prescription. Other stakeholders,
however, agreed with the inclusion of drug products provided pursuant
to a prescription within the definition of ``distribution'' and
maintained that this interpretation was important to protect the public
health.
    After considering these comments and the public health objectives
of section 503A(b)(3)(B) of the FD&C Act, we have proposed to revise
the definition of distribution to exclude dispensing that occurs at the
facility in which the drug was compounded. We intend to consider that
when a drug is picked up in this way, dispensing, but not distribution,
occurs for purposes of calculating ``inordinate amounts'' under the MOU
or applying the 5 percent limit in section 503A(b)(3)(B)(ii) of the
FD&C Act.
    FDA proposes that in-person dispensing, where the transaction
between the compounder and the patient is completed without the
compounded drug leaving the facility in which it was compounded, is
appropriately overseen, primarily, by the State outside the context of
the MOU, regardless of whether the compounded drug product subsequently
leaves the State. Such an intrastate, local transaction generally
indicates a close connection among the patient, compounder, and
prescriber. By contrast, transactions by mail often have a less direct
nexus among the patient, compounder, and prescriber than in-

person pickups and would be considered ``distributions.''
    Under this revised proposed definition, drugs dispensed in-person
that are later taken out of State would not contribute to reaching the
threshold for inordinate amounts that would need to be reported to FDA
under the MOU. Nor would complaints associated with compounded drug
products dispensed this way and subsequently taken out of State be
subject to the complaint investigation provisions of the MOU. FDA
expects that, in practice, the State in which the initial transaction
occurred would handle such complaints. The State may, in its
discretion, notify FDA of the complaint. We recognize that including
in-person dispensing in the definition of ``distribution'' would result
in complex tracking issues in instances when a patient subsequently
crosses State lines. Under the proposed revised definition, the
compounder would not need to track where the patient takes the
compounded drug product after it is in the patient's possession.
    FDA is not persuaded by comments on the 2015 draft standard MOU
urging the Agency to interpret ``distribution'' and ``dispensing'' to
be entirely separate activities for purposes of section 503A(b)(3)(B)
of the FD&C Act. These comments recommend using definitions for these
terms used elsewhere in the FD&C Act and FDA regulations, and generally
conclude that distribution does not include the transfer of a drug
pursuant to a prescription.
    The conditions in section 503A, including section 503A(b)(3)(B),
must be interpreted consistent with the prescription requirement in
section 503A(a) of the FD&C Act. If we were to interpret the word
``distribution'' to apply only if a drug is provided without a
prescription, it would mean that drug products compounded under section
503A of the FD&C Act are excluded from regulation under the MOU and the
5 percent limit, because to qualify for the exemptions under section
503A, a compounder must obtain a valid prescription order for an
individually identified patient. For the reasons stated previously in
section IV.B, we believe this would achieve the opposite of what
Congress intended. 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.''
    Nor is there anything to suggest that Congress understood
distributed and dispensed to be mutually exclusive categories rather
than overlapping categories for purposes of section 503A of the FD&C
Act. Section 503A(b)(3)(B) of the FD&C Act does not define
``distribution'' to exclude dispensing, which Congress has done
elsewhere when that was its intention.\4\ The definition proposed by
comments would write an exclusion for dispensing, in its entirety, into
the statute where Congress did not. Indeed, with respect to comments
suggesting that drugs dispensed pursuant to prescriptions could not
also be ``distributed,'' we note that, in section 503A(b)(3)(B) of the
FD&C Act, Congress specifically contemplated that prescription orders
could be ``distributed'' when it directed the Agency to count the
number of prescription orders that pharmacists and prescribers
distributed.
---------------------------------------------------------------------------

    \4\ In other (non-compounding) contexts, where it would further
a regulatory purpose, Congress and the Agency have specifically
defined ``distribute'' to exclude dispensing. See, for example,
section 581(5) of the FD&C Act (21 U.S.C. 360eee(5)), which applies
to Title II of the DQSA, and 21 CFR 208.3. Section 503A of the FD&C
Act does not contain a similar definition or a similar specific
direction to exclude dispensing from the meaning of distribution. We
also note that these definitions were adopted for provisions that
focus on conventionally manufactured drug products, which assign
different obligations to dispensers than to wholesalers, packagers,
or other intermediaries in light of the different role that
dispensers play with respect to product labeling and the drug
distribution chain. In contrast, section 503A of the FD&C Act
focuses on compounded drugs, and the reasons for defining
``distribution'' to exclude dispensing in Title II of the DQSA or
part 208 do not apply.
---------------------------------------------------------------------------

V. Other Issues

A. Development of a Standard MOU

    A number of comments on the 1999 draft standard MOU, the 2013 draft
503A guidance, and the 2015 draft standard MOU suggested that FDA
negotiate MOUs with individual States, rather than develop a standard
MOU. Section 503A of the FD&C Act requires the Agency to develop a
standard MOU for use by the States. Furthermore, it would be
impractical to develop an individualized MOU with every State, and
creating individualized MOUs would create a patchwork of regulation of
interstate distribution by compounders seeking to qualify for the
exemptions under section 503A of the FD&C Act. This would be confusing
to the health care community, as well as regulators.

B. Exemptions From the Interstate Distribution Provisions

    Some comments on the 2013 draft 503A guidance and the 2015 draft
standard MOU requested that we consider exempting certain drug products
or types of compounding entities from the threshold in the MOU and the
5 percent limit. For example, some comments recommended that we exempt
nonsterile products.
    American consumers rely on the FDA drug approval process to ensure
that medications have been evaluated for safety and effectiveness
before they are marketed in the United States. Drugs made by
compounders, including those made at outsourcing facilities, are not
FDA-approved. This means that they have not undergone premarket review
of safety, effectiveness, or manufacturing quality. Therefore, when an
FDA-approved drug is commercially available, FDA recommends that
practitioners prescribe the FDA-approved drug rather than a compounded
drug unless the prescribing practitioner has determined that a
compounded product is necessary for the particular patient and would
provide a significant difference for the patient as compared to the
FDA-approved commercially available drug product.
    In section 503A of the FD&C Act, Congress enacted several
conditions to differentiate compounders from conventional manufacturers
and provided that only if the compounders meet those conditions can
they qualify for the exemptions from the drug approval requirements in
section 505 of the FD&C Act. One of those conditions relates to
limitations on the interstate distribution of compounded drug products,
and FDA intends to enforce those provisions to differentiate
compounding that qualifies for the exemptions from conventional
manufacturing in the guise of compounding that does not, and will apply
the conditions to all types of drugs and all categories of compounding.

C. Information Sharing Between States and FDA

    The revised draft standard MOU provides that States will agree to
notify FDA of any complaint relating to a compounded drug product
distributed outside the State involving a serious adverse drug
experience or serious product quality issue, and provide information
about those events and issues. The revised draft standard MOU also
provides that States will notify FDA if they identify a pharmacy or
physician

within their jurisdiction that has distributed inordinate amounts of
compounded drug products interstate.
    FDA regularly posts on its compounding website information about
enforcement and other actions related to compounders that violate the
FD&C Act, and it is obligated to share certain information with States
under section 105 of the DQSA. In addition to these measures, FDA is
taking steps to proactively share information with States about
complaints that it receives, consistent with Federal laws governing
information disclosure.

D. Enforcement of the 5 Percent Limit on Distribution of Compounded
Drug Products Out of the State in Which They Are Compounded

    In the 503A guidance, FDA stated that it does not intend to enforce
the 5 percent limit on distribution of compounded drug products outside
of the State in which they are compounded until 90 days after FDA has
finalized a standard MOU and made it available to the States for their
consideration and signature. Most comments on the 2013 draft 503A
guidance said this period was too short, but did not recommend a
specific alternative. A few comments recommended a different timeframe,
one recommending 120 days and another recommending 365 days. The 1997
Senate Committee Report for the Food and Drug Administration
Modernization Act suggests that a 180-day period for States to decide
whether to sign might be appropriate.\5\ Consistent with the 2015 draft
standard MOU, the Agency proposes a 180-day period after the final
standard MOU is made available for signature before FDA will enforce
the 5 percent limit in States that have not signed the MOU, and invites
public comment on whether this is an appropriate timeframe. FDA will
announce at the time it publishes the final standard MOU and makes it
available for signature when it intends to begin enforcing the 5
percent limit in States that do not sign.
---------------------------------------------------------------------------

    \5\ ``[U]ntil the State . . . enters into a memorandum of
understanding (MOU) with the Secretary or 180 days after the
development of the standard MOU, whichever comes first, the [section
503A] exemption shall not apply if inordinate quantities of
compounded products are distributed outside of the State in which
the compounding pharmacy or physician is located.'' (U.S. Senate
Committee Report)
---------------------------------------------------------------------------

E. Physician Compounding

    Several comments advised that State boards of pharmacy do not
oversee physician compounding and would not be able to agree to perform
the obligations under the 2015 draft standard MOU with respect to
oversight of physician compounding.
    FDA recognizes that physicians often do not indicate, as part of
their State licensure, that they compound drug products, and that there
may not be routine mechanisms, such as inspections, to determine the
extent to which such physicians distribute compounded drugs interstate.
It is also FDA's understanding that physicians who compound drugs
generally do so for their own patients, within their own professional
practice, and they distribute or dispense them intrastate. However,
there is still the potential for widespread harm if physicians ship
large percentages of compounded drugs interstate without State
investigation of complaints associated with those compounded drugs.
Accordingly, under the revised draft standard MOU, States would agree
to: (1) Notify FDA and the appropriate State agency if they receive
information about serious adverse drug experiences or serious product
quality issues associated with drugs compounded by physicians and (2)
if they become aware of a physician distributing compounded drugs
interstate, coordinate with the regulator of physician compounding
within the State to determine whether the physician distributes
inordinate amounts of compounded drug products interstate and notify
FDA of physicians that do so.

F. Prescription Orders

    Commenters expressed that the meaning of the term ``units,'' which
is used in the 2015 draft standard MOU to calculate the 30 percent
limit, was unclear to them.
    In the revised draft standard MOU, FDA has replaced the term
``unit'' with ``prescription order'' (i.e., the inordinate amounts
calculation uses numbers of prescription orders for compounded drug
products). ``Prescription orders'' includes chart orders for patients
made in a healthcare setting. For purposes of this MOU, each refill is
considered to be a new prescription order.

VI. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C.
3501-3520), Federal Agencies must obtain approval from the Office of
Management and Budget (OMB) for each collection of information they
conduct or sponsor. ``Collection of information'' is defined in 44
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or
requirements that members of the public submit reports, keep records,
or provide information to a third party. Section 3506(c)(2)(A) of the
PRA (44 U.S.C. 3506(c)(2)(A)), requires Federal Agencies to provide a
60-day notice in the Federal Register for each proposed collection of
information before submitting the collection to OMB for approval. To
comply with this requirement, FDA is publishing notice of the proposed
collection of information set forth in this document.
    With respect to the following collection of information, FDA
invites comments on these topics: (1) Whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information collected; and (4) ways to
minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
    Section 503A of the FD&C Act describes, among other things, the
circumstances under which certain drug products compounded by a
licensed pharmacist or licensed physician are exempt from certain
sections of the FD&C Act. One of the conditions to qualify for the
exemptions listed in section 503A of the FD&C Act is that: (1) The drug
product is compounded in a State that has entered into an MOU with FDA
that addresses the distribution of inordinate amounts of compounded
drug products interstate and provides for appropriate investigation by
a State agency of complaints relating to compounded drug products
distributed outside such a State or (2) if the drug product is
compounded in a State that has not entered into such an MOU, the
licensed pharmacist, pharmacy, or physician does not distribute, or
cause to be distributed, compounded drug products out of the State in
which they are compounded, more than 5 percent of the total
prescription orders dispensed or distributed by such pharmacy or
physician (see section 503A(b)(3)(B)(i) and (ii).
    Section 503A(b)(3) directs FDA, in consultation with the NABP, to
develop a standard MOU for use by States in complying with the
provisions concerning the interstate distribution of inordinate amounts
of compounded drug products interstate and appropriate investigation by
a State agency of complaints relating to drug products compounded in
the State and distributed outside such State.

    The revised draft standard MOU contains the information collections
that must be approved by OMB under the PRA. These information
collections are described in this section of the document. For purposes
of this analysis, FDA assumes that 45 States will sign the standard MOU
with FDA.
    Under section III.a. of the revised draft standard MOU, the State
will notify FDA by email at [email protected] as soon as possible,
but no later than 3 business days, after receiving any complaint
relating to a compounded drug product distributed outside the State
involving a serious adverse drug experience or serious product quality
issue. The notification will include the following information: (1) The
name and contact information of the complainant; (2) the name and
address of the pharmacy or physician that is the subject of the
complaint; (3) a description of the complaint, including a description
of any compounded drug product that is the subject of the complaint;
and (4) the State's initial assessment of the validity of the complaint
relating to a compounded drug product distributed outside the State, if
available. In addition, the States will maintain records of the
complaints they receive, the investigation of each complaint, and any
response to or action taken as a result of a complaint, beginning when
the State receives notice of the complaint. The States will maintain
these records for at least 3 years, beginning on the date of final
action or the date of a decision that the complaint requires no action.
    Based on our knowledge of State regulation of compounding practices
and related complaints, we estimate that annually a total of
approximately 45 States (``no. of respondents'' in table 1, row 2) will
notify FDA within 3 business days of receiving any complaint relating
to a compounded drug product distributed outside the State involving a
serious adverse drug experience or serious product quality issue. We
estimate that each State will notify FDA annually of approximately 3
complaints it receives (``no. of responses per respondent'' in table 1,
row 2), for a total of 135 notifications of complaints sent to FDA
(``total annual responses'' in table 1, row 2). We estimate that
preparing and submitting this information to us as described in the MOU
will take approximately 0.5 hours per response (``average burden per
response'' in table 1, row 1), for a total of 67.5 hours (``total
hours'' in table 1, row 2).
    We also estimate that a total of approximately 45 States (``no. of
recordkeepers'' in table 2) will prepare and maintain records for 3
years of the complaints they receive, investigations of complaints, and
any State action taken or response to complaints. We estimate that each
State will receive approximately 3 complaints annually and will prepare
and maintain approximately 5 records per each complaint the State
receives, for a total of 15 records per State (``no. of records per
recordkeeper'' in table 2), and a total of 675 records annually across
all States (``total annual records'' in table 2). We further estimate
that preparing and maintaining these records will take approximately 1
hour per record (``average burden per recordkeeping (in hours)'' in
table 2), for a total of 675 hours (``total hours'' in table 2).
    Under section III.b of the revised draft standard MOU, on an annual
basis (at minimum), the State will identify, using surveys, reviews of
records during inspections, or other mechanisms available to the State,
compounding pharmacies that distribute inordinate amounts of compounded
drug products interstate by collecting information regarding the total
number of prescription orders for compounded drug products distributed
or dispensed intrastate and the total number of prescription orders for
compounded drug products distributed interstate. Similarly, the State
will engage in the same efforts to collect this information if it
becomes aware of a physician who is distributing compounded drug
products interstate. If a pharmacy or physician has been identified as
distributing inordinate amounts of compounded drug products interstate,
the State will also collect information regarding: (1) The total number
of prescription orders for sterile compounded drug products distributed
out of State; (2) the number of States in which the compounding
pharmacy or physician is licensed or number of States into which the
compounding pharmacy or physician distributes compounded drug products;
and (3) whether the State inspected for and found during its most
recent inspection that the compounding pharmacy or physician
distributed compounded drug products without valid prescriptions for
individually identified patients.
    The States will notify FDA by email at [email protected] within
30 days of identifying a pharmacy/physician within their jurisdiction
that has distributed inordinate amounts of compounded drug products
interstate, as described in the revised draft standard MOU. The
notification should include the name and address of the pharmacy/
physician and the information that the States collected, described in
the previous paragraph.
    We estimate that annually a total of approximately 45 States (``no.
of respondents'' in table 1, row 3) will identify compounding
pharmacies or physicians that distribute inordinate amounts of
compounded drug products interstate. We estimate that each State will
perform surveys or inspections of 150 pharmacies or physicians to
identify this information (``no. of responses per respondent'' in table
1, row 3). We estimate that this will take approximately 1 hour per
response (``average burden per response'' in table 1, row 3), for a
total of 6,750 hours (``total hours'' in table 1, row 3). We estimate
that annually a total of 40 States (``no. of respondents'' in table 1,
row 4) will notify FDA of their finding that a pharmacy or physician
has distributed inordinate amounts of compounded drug products
interstate. We estimate that each State will notify FDA annually of
approximately 50 findings it makes (``no. of responses per respondent''
in table 1, row 4), for a total of 200 notifications (``total annual
responses'' in table 1, row 4). We estimate that preparing and
submitting this information to FDA as described in the MOU will take
approximately 0.5 hours per response (``average burden per response''
in table 1, row 4), for a total of 100 hours (``total hours'' in table
1, row 4).
    Under section V of the revised draft standard MOU, a State may
designate a new liaison to the MOU by notifying FDA's administrative
liaison in writing. If a State's liaison becomes unavailable to fulfill
its functions under the MOU, the State will name a new liaison within 2
weeks and notify FDA.
    We estimate that annually a total of approximately 13 States (``no.
of respondents'' in table 1, row 5) will notify FDA of a new liaison to
the MOU. We estimate that each State will submit to FDA annually
approximately 1 notification of a new liaison (``no. of responses per
respondent'' in table 1, row 5), for a total of 13 notifications of a
new liaison (``total annual responses'' in table 1, row 5). We estimate
that preparing and submitting each notification as described in the MOU
will take approximately 0.2 hours per response (``average burden per
response'' in table 1, row 5), for a total of 2.6 hours (``total
hours'' in table 1, row 5).
    Under section VI of the revised draft standard MOU, a State may
terminate its participation in the MOU by submitting to FDA a 30-day
notice of termination.
    We estimate that annually a total of approximately 1 State (``no.
of

respondents'' in table 1, row 6) will notify FDA that it intends to
terminate its participation in the MOU. We estimate that this State
will submit to FDA annually approximately 1 notification of termination
(``no. of responses per respondent'' in table 1, row 6), for a total of
1 notification (``total annual responses'' in table 1, row 6). We
estimate that preparing and submitting the notification as described in
the MOU will take approximately 0.2 hours per notification (``average
burden per response'' in table 1, row 6), for a total of 0.2 hours
(``total hours'' in table 1, row 6).
    Under section VI of the revised draft standard MOU, if a State does
not adhere to the provisions of the MOU, FDA may post a 30-day notice
of termination on its website. As a result of this action by FDA, the
State will notify all licensed pharmacists, pharmacies and physicians
within the State of the termination and advise them that compounded
drug products may be distributed (or caused to be distributed) out of
the State only in quantities that do not exceed 5 percent of the total
prescription orders dispensed or distributed by such pharmacy or
physician.
    We estimate that annually a total of approximately 1 State (``no.
of respondents'' in table 3) will submit to the pharmacists,
pharmacies, and physicians in its State 1 notification of termination
as described in the MOU (``no. of disclosures per respondent'' in table
3), for a total of 1 notification of termination (``total annual
disclosures'' in table 3). We estimate that preparing and submitting
each notification will take approximately 1 hour per notification
(``average burden per disclosure (in hours)'' in table 3), for a total
of 1 hour (``total hours'' in table 3).
    FDA estimates the burden of this collection of information as
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                            Number of
 Compounding MOU between FDA and States     Number of     responses per   Total annual             Average burden per response              Total hours
                                           respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
State notifies FDA of compounding                    45               3             135  0.5 (30 minutes)...............................            67.5
 complaints it receives.
State identifies pharmacies or                       45             150           6,750  1..............................................           6,750
 physicians that distribute inordinate
 amounts of compounded drugs interstate
 using surveys or inspections.
State notifies FDA of the distribution               40              50             200  0.5 (30 minutes)...............................             100
 of inordinate amounts of compounded
 drug products.
State notifies FDA of a new liaison to               13               1              13  0.2 (12 minutes)...............................             2.6
 the MOU.
State notifies FDA of its intent to                   1               1               1  0.2 (12 minutes)...............................             0.2
 terminate participation in the MOU.
                                        ----------------------------------------------------------------------------------------------------------------
    Total..............................  ..............  ..............  ..............  ...............................................         6,920.3
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

                               Table 2--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                                                Average burden
 Compounding MOU between FDA and     Number of       Number of     Total annual         per
             States                recordkeepers    Records per       records      recordkeeping    Total hours
                                                   recordkeeper                     (in hours)
----------------------------------------------------------------------------------------------------------------
State recordkeeping for 3 years               45              15             675               1             675
 of compounding complaints......
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............             675
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

                           Table 3--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                    Average burden
 Compounding MOU between FDA and     Number of      disclosures    Total annual   per disclosure    Total hours
             States                 respondents   per respondent    disclosures     (in hours)
----------------------------------------------------------------------------------------------------------------
State notification to                          1               1               1               1               1
 pharmacists, pharmacies, and
 physicians that its
 participation in the MOU has
 been terminated by FDA.........
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............               1
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

III. Electronic Access

    Persons with access to the internet may obtain the draft MOU at
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or
https://www.regulations.gov.

    Dated: August 31, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-19461 Filed 9-7-18; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register Volume 78, Number 103 (Wednesday, May 29, 2013)]
[Proposed Rules]
[Pages 32213-32214]
[FR Doc No: 2013-12707]

-----------------------------------------------------------------------

DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 71

[Docket No. FAA-2013-0359; Airspace Docket No. 13-AEA-7]

Proposed Amendment of Class E Airspace; Bedford, PA

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Notice of proposed rulemaking (NPRM).

-----------------------------------------------------------------------

SUMMARY: This action proposes to amend Class E Airspace at Bedford, PA,
as the St. Thomas VORTAC has been decommissioned, requiring airspace
redesign at Bedford County Airport. This action would enhance the
safety and airspace management of Instrument Flight Rules (IFR)
operations at the airport. This action also would update the geographic
coordinates of the airport.

DATES: Comments must be received on or before July 15, 2013.

ADDRESSES: Send comments on this rule to: U.S. Department of
Transportation, Docket Operations, West Building Ground Floor, Room
W12-140, 1200 New Jersey SE., Washington, DC 20590-0001; Telephone: 1-
800-647-5527; Fax:<PHONE_NUMBER>. You must identify the Docket Number
FAA-2013-0359; Airspace Docket No. 13-AEA-7, at the beginning of your
comments. You may also submit and review received comments through the
Internet at http:[sol][sol]www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: John Fornito, Operations Support
Group, Eastern Service Center, Federal Aviation Administration, P.O.
Box 20636, Atlanta, Georgia 30320; telephone<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Comments Invited

    Interested persons are invited to comment on this rule by
submitting such written data, views, or arguments, as they may desire.
Comments that provide the factual basis supporting the views and
suggestions presented are particularly helpful in developing reasoned
regulatory decisions on the proposal. Comments are specifically invited
on the overall regulatory, aeronautical, economic, environmental, and
energy-related aspects of the proposal.
    Communications should identify both docket numbers (FAA Docket No.
FAA-2013-0359; Airspace Docket No. 13-AEA-7) and be submitted in
triplicate to the Docket Management System (see ADDRESSES section for
address and phone number). You may also submit comments through the
Internet at http:[sol][sol]www.regulations.gov.
    Persons wishing the FAA to acknowledge receipt of their comments on
this action must submit with those comments a self-addressed stamped
postcard on which the following statement is made: ``Comments to Docket
No. FAA-2013-0359; Airspace Docket No. 13-AEA-7.'' The postcard will be
date/time stamped and returned to the commenter.
    All communications received before the specified closing date for
comments will be considered before taking action on the proposed rule.
The proposal contained in this notice may be changed in light of the
comments received. A report summarizing each substantive public contact
with FAA personnel concerned with this rulemaking will be filed in the
docket.

Availability of NPRMs

    An electronic copy of this document may be downloaded from and
comments submitted through http:[sol][sol]www.regulations.gov. Recently
published rulemaking documents can also be accessed through the FAA's
Web page at http:[sol][sol]www.faa.gov/airports--airtraffic/air--
traffic/publications/airspace--amendments/.
    You may review the public docket containing the proposal, any
comments received, and any final disposition in person in the Dockets
Office (see the ADDRESSES section for address and phone number) between
9:00 a.m. and 5:00 p.m., Monday through Friday, except Federal
Holidays. An informal docket may also be examined between 8:00 a.m. and
4:30 p.m., Monday through Friday, except Federal Holidays at the office
of the Eastern Service Center, Federal Aviation Administration, Room
350, 1701 Columbia Avenue, College Park, Georgia 30337.
    Persons interested in being placed on a mailing list for future
NPRM's should contact the FAA's Office of Rulemaking,<PHONE_NUMBER>,
to request a copy of Advisory circular No. 11-2A, Notice of Proposed
Rulemaking distribution System, which describes the application
procedure.

The Proposal

    The FAA is considering an amendment to Title 14, Code of Federal
Regulations (14 CFR) part 71 to amend Class E airspace extending upward
from 700 feet above the surface at Bedford County Airport, Bedford, PA.
Airspace reconfiguration to within a 12.5-mile radius of the airport is
necessary due to the decommissioning of the St. Thomas VORTAC, and for
continued safety and management of IFR operations at the airport. The
geographic coordinates of the airport would be adjusted to coincide
with the FAAs aeronautical database.
    Class E airspace designations are published in Paragraph 6005 of
FAA Order 7400.9W, dated August 8, 2012, and effective September 15,
2012, which is incorporated by reference in 14 CFR 71.1. The Class E
airspace designation listed in this document will be published
subsequently in the Order.
    The FAA has determined that this proposed regulation only involves
an established body of technical regulations for which frequent and
routine amendments are necessary to keep them operationally current.
It, therefore, (1) is not a ``significant

regulatory action'' under Executive Order 12866; (2) is not a
``significant rule'' under DOT Regulatory Policies and Procedures (44
FR 11034; February 26, 1979); and (3) does not warrant preparation of a
Regulatory Evaluation as the anticipated impact is so minimal. Since
this is a routine matter that only affects air traffic procedures and
air navigation, it is certified that this proposed rule, when
promulgated, does not have a significant economic impact on a
substantial number of small entities under the criteria of the
Regulatory Flexibility Act.
    The FAA's authority to issue rules regarding aviation safety is
found in Title 49 of the United States Code. Subtitle I, Section 106
describes the authority of the FAA Administrator. Subtitle VII,
Aviation Programs, describes in more detail the scope of the agency's
authority. This proposed rulemaking is promulgated under the authority
described in Subtitle VII, Part, A, Subpart I, Section 40103. Under
that section, the FAA is charged with prescribing regulations to assign
the use of airspace necessary to ensure the safety of aircraft and the
efficient use of airspace. This proposed regulation is within the scope
of that authority as it would amend Class E airspace at Bedford County
Airport, Bedford, PA.
    This proposal would be subject to an environmental analysis in
accordance with FAA Order 1050.1E, ``Environmental Impacts: Policies
and Procedures'' prior to any FAA final regulatory action.

Lists of Subjects in 14 CFR Part 71

    Airspace, Incorporation by reference, Navigation (air).

The Proposed Amendment

    In consideration of the foregoing, the Federal Aviation
Administration proposes to amend 14 CFR part 71 as follows:

PART 71--DESIGNATION OF CLASS A, B, C, D, AND E AIRSPACE AREAS; AIR
TRAFFIC SERVICE ROUTES; AND REPORTING POINTS

0
1. The authority citation for part 71 continues to read as follows:

    Authority:  49 U.S.C. 106(g); 40103, 40113, 40120; E.O. 10854,
24 FR 9565, 3 CFR, 1959-1963 Comp., p. 389.

Sec.  71.1  [Amended]

0
2. The incorporation by reference in 14 CFR 71.1 of Federal Aviation
Administration Order 7400.9W, Airspace Designations and Reporting
Points, dated August 8, 2012, effective September 15, 2012, is amended
as follows:

Paragraph 6005. Class E Airspace Areas Extending Upward from 700
feet or More Above the Surface of the Earth.

* * * * *

AEA PA E5 Bedford, PA [Amended]

Bedford County Airport, PA
    (Lat. 40[deg]05'10'' N., long. 78[deg]30'49''W.)
    That airspace extending upward from 700 feet above the surface
within a 12.5-mile radius of Bedford County Airport.

    Issued in College Park, Georgia, on May 21, 2013.
Jackson Allen,
Acting Manager, Operations Support Group, Eastern Service Center, Air
Traffic Organization.
[FR Doc. 2013-12707 Filed 5-28-13; 8:45 am]
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[Federal Register Volume 81, Number 131 (Friday, July 8, 2016)]
[Notices]
[Pages 44628-44629]
[FR Doc No: 2016-16152]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-N-0001]

Regional Public Workshop on the International Council for
Harmonization of Technical Requirements for Pharmaceuticals for Human
Use Q3D Implementation of Guideline for Elemental Impurities; Public
Workshop

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a public
workshop entitled: Regional Public Workshop on ICH Q3D Implementation
of Guideline for Elemental Impurities. The purpose of the public
workshop is to elaborate key aspects of the ICH Guideline Q3D:
Guideline on Elemental Impurities in order facilitate a harmonized
interpretation and implementation by industry and regulators. It is not
intended to provide additional guidance beyond the scope of Q3D. The
meeting will take place on the FDA campus and also be broadcast on the
Web allowing participants to join in person or via the Web.

DATES: The public workshop will be held on August 22 and 23, from 9
a.m. to 5 p.m., EST. See the SUPPLEMENTARY INFORMATION section for
information on how to register.

ADDRESSES: The public workshop will be held at 10903 New Hampshire
Ave., Bldg. 31, Rm. 1503B/C, Silver Spring, MD 20993. The entrance for
the public workshop participants (non-FDA employees) is through
Building 1 where routine security check procedures will be performed.
For parking and security information, please refer to http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.

FOR FURTHER INFORMATION CONTACT: Amanda Roache, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 1176, Silver
Spring, MD 20993,<PHONE_NUMBER>, email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: The ICH brings together regulatory
authorities and pharmaceutical industry to discuss scientific and
technical aspects of drug registration. The ICH's mission is to achieve
greater harmonization worldwide to ensure that safe, effective, and
high quality medicines are developed and registered in the most
resource-efficient manner. The ICH Q3D Guideline was developed by the
ICH to provide a global policy for limiting elemental impurities
qualitatively and quantitatively in drug products and ingredients.
Following finalization of this Guideline, an Implementation Working
Group was established to develop a comprehensive training program and
supporting documents sponsored by ICH to ensure the proper
interpretation and effective utilization

by industry and regulators alike to enable a harmonized and smooth
implementation of Q3D on a global basis.
    The U.S. regional workshop is intended to clarify key aspects of
ICH Q3D: Guideline on Elemental Impurities by elaborating on those key
topics. It will include: (1) A discussion of how to apply Q3D concepts
to routes of administration, not addressed in Q3D, (2) justification
for elemental impurity levels higher than an established permissible
daily exposure (PDE) (3) application of Q3D concepts to determine safe
levels of elements not included in Q3D, (4) discussion of the rationale
for limits on large volume parenterals, (5) elaboration of the concepts
outlined in the Q3D Sections on Risk Assessment and Control of
Elemental Impurities and (6) options for converting between PDEs and
concentrations.
    In addition, case studies may be presented to illustrate the
concepts described previously, and frequently asked questions will be
discussed. The presentation of the material will follow the modules
that are available on the ICH Web site, www.ich.org, and will include
time for questions and discussion. Breakout sessions will be provided
to discuss key topics and provide feedback to participants. Material
will be presented by members of the ICH Q3D Implementation Working
Group. The agenda for the workshop will be made available on the
internet at http://www.fda.gov/Drugs/NewsEvents/ucm498553.htm.
    Registration: If you wish to attend this meeting, visit the
following Web site to register: https://www.eventbrite.com/e/regional-public-workshop-on-ich-q3d-implementation-of-guideline-for-elemental-impurities-tickets-25492458630. Please register by August 15, 2016. If
you are unable to attend the meeting in person, you can register to
view a live Webcast on the meeting. You will be asked to indicate in
your registration if you plan to attend in person or via the Webcast.
Your registration must also contain your complete contact information,
including name, title, affiliation, address, email address, and phone
number. Registrations may be limited, so early registration is
recommended. Registration is free and will be on a first-come, first-
served basis. However, the number of participants from each
organization may be limited based on space limitations. Registrants
will receive confirmation once they have been accepted. Onsite
registration on the day of the meeting will be based on space
availability. If you need special accommodations because of a
disability, please contact Amanda Roache (see FOR FURTHER INFORMATION
CONTACT) at least 7 days before the meeting.

    Dated: July 1, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-16152 Filed 7-7-16; 8:45 am]
 BILLING CODE 4164-01-P