FDA Briefing Document Pharmacy Compounding Advisory Committee (PCAC)

224 Pages·2016·6.04 MB·English

FDA Briefing Document

Pharmacy Compounding Advisory Committee (PCAC)
Meeting

June 23, 2016

The attached package contains background information prepared by the Food and Drug
Administration (FDA) for the panel members of the Pharmacy Compounding Advisory
Committee (advisory committee). We are bringing certain compounding issues to this advisory
committee to obtain the committee’s advice. The background package may not include all issues
relevant to the final regulatory recommendation and instead is intended to focus on issues
identified by the Agency for discussion by the advisory committee. The FDA background
package often contains assessments and/or conclusions and recommendations written by
individual FDA reviewers. Such conclusions and recommendations do not necessarily represent
the final position of the individual reviewers, nor do they necessarily represent the final position
of the Review Division or Office. The FDA does not intend to issue a final determination on the
issues at hand until input from the advisory committee process has been considered, all reviews
have been finalized, consultation with the United States Pharmacopeia has occurred, and public
comment has been considered through notice and comment rulemaking. The final determination
may be affected by issues not discussed at the advisory committee meeting.
Table of Contents

I. Introduction ................................................................................................................... 3
A. Bulk Drug Substances That Can Be Used by Compounders under Section 503A
.............................................................................................................................. 3
B. Expanded Access to Investigational New Drugs ................................................. 4
II. Substances Nominated for Inclusion on the Section 503A Bulk Drug Substances List
(in order of discussion at the meeting) .......................................................................... 5
III. Draft Points to Consider................................................................................................ 7

FDA Briefing Document Page 2
June 23, 2016
I. Introduction

Section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) 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 505 (concerning
the approval of drugs under new drug applications or abbreviated new drug applications);
section 502(f)(1) (concerning the labeling of drugs with adequate directions for use); and
section 501(a)(2)(B) (concerning current good manufacturing practice requirements).

On November 27, 2013, President Obama signed the Drug Quality and Security Act,
legislation that contains important provisions relating to the oversight of compounding of
human drugs. Title I of this law, the Compounding Quality Act, created a new section
503B of the FD&C Act under which a compounder can elect to register as an outsourcing
facility. Registered outsourcing facilities can compound drugs without receiving patient
specific prescriptions or orders. If the conditions under section 503B of the FD&C Act
are satisfied, drugs compounded by or under the direct supervision of a licensed
pharmacist in a registered outsourcing facility may qualify for exemptions from the new
drug approval requirements (section 505 of the FD&C Act), the requirement to label
products with adequate directions for use (section 502(f)(1) of the FD&C Act) and the
Drug Supply Chain Security Act (section 582 of the FD&C Act). Outsourcing facilities
remain subject to current good manufacturing practice (CGMP) requirements.

A. Bulk Drug Substances That Can Be Used by Compounders
under Section 503A

One of the conditions that must be met for a drug product that is compounded using bulk
drug substances to qualify for the exemptions in Section 503A of the Act is that a
licensed pharmacist or licensed physician compounds the drug product using bulk drug
substances that:

(1) Comply with the standards of an applicable United States Pharmacopeia
(USP) or National Formulary (NF) monograph, if a monograph exists, and the
USP chapter on pharmacy compounding;
(2) If such a monograph does not exist, are drug substances that are components
of drugs approved by the Secretary; or
(3) If such a monograph does not exist and the drug substance is not a component
of a drug approved by the Secretary, appears on a list developed by the
Secretary through regulations issued by the Secretary under subsection (c) of
section 503A.

(See section 503A(b)(1)(A)(i) of the FD&C Act).

FDA Briefing Document Page 3
June 23, 2016
FDA is considering those substances nominated for inclusion on the list of bulk drug
substances that can be used to compound drug products under section 503A of the FD&C
Act. As discussed at the February 2015 PCAC meeting, in the July 2014 Federal
Register notice (79 FR 37747) (July 2, 2014) soliciting nominations for the section 503A
bulk drug substances list, FDA proposed the following criteria to evaluate the nominated
substances:

(1) The physical and chemical characterization of the substance;
(2) Any safety issues raised by the use of the substance in compounded drug
products;
(3) Historical use of the substance in compounded drug products, including
information about the medical condition(s) the substance has been used to
treat and any references in peer-reviewed medical literature; and
(4) The available evidence of effectiveness or lack of effectiveness of a drug
product compounded with the substance, if any such evidence exists.

The agency is considering each criterion in the context of the others and balancing them,
on a substance-by-substance basis, in deciding whether a particular substance is
appropriate for inclusion on the list.

B. Expanded Access to Investigational New Drugs

Expanded access, sometimes referred to as “compassionate use,” is the use of an
investigational drug outside of a clinical trial, including for emergency use, for the
purpose of treating a patient or patients with serious or life-threatening disease(s) or
condition(s) who have no acceptable medical options. The use of an investigational drug
under expanded access is subject to all applicable requirements regarding informed
consent and institutional review board (IRB) review.

At previous meetings, there have been discussions about the use of an IND as an option
for patients who seek to use drugs that are nominated for, but not placed on, the 503A
and 503B bulks lists. At this meeting, the Agency plans to describe additional details
about the expanded access program. Further information on the use of INDs is available
on the Agency’s website at:

http://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse
/default.htm

FDA Briefing Document Page 4
June 23, 2016
II. Substances Nominated for Inclusion on the Section 503A
Bulk Drug Substances List (in order of discussion at the
meeting)

A. Chrysin (Tab 1)

1. Nominations (Tab 1a)
(a) Fagron
(b) International Academy of Compounding Pharmacists
(c) National Community Pharmacists Association

2. FDA Review (Tab 1b)

B. Cesium Chloride (Tab 2)

1. Nominations (Tab 2a)
(a) American Association of Naturopathic Physicians
(b) Alliance for Natural Health USA
(c) Integrative Medical Consortium
(d) McGuff Compounding Pharmacy Services, Inc.

2. FDA Review (Tab 2b)

C. Sodium Dichloroacetate (Tab 3)

1. Nominations (Tab 3a)
(a) McGuff Compounding Pharmacy Services, Inc.
(b) Alliance for Natural Health USA
(c) Integrative Medical Consortium
(d) American Association of Naturopathic Physicians

2. FDA Review (Tab 3b)

D. Pyruvic Acid (Tab 4)

1. Nominations (Tab 4a)
(a) Fagron

2. FDA Review (Tab 4b)

FDA Briefing Document Page 5
June 23, 2016
E. Tea Tree Oil (Tab 5)

1. Nominations (Tab 5a)
(a) National Community Pharmacists Association
(b) International Academy of Compounding Pharmacists

2. FDA Review (Tab 5b)

F. 2,3-Dimercapto-1-propanesulfonic acid (DMPS) (Tab 6)

1. Nominations (Tab 6a)
(a) Alliance for Natural Health USA
(b) American Association of Naturopathic Physicians
(c) Integrative Medical Consortium
(d) McGuff Compounding Pharmacy Services, Inc.
(e) International Academy of Compounding Pharmacists

2. FDA Review (Tab 6b)

FDA Briefing Document Page 6
June 23, 2016
III. Draft Points to Consider

A. June 23, 2016, a.m. session

Draft points to consider for the PCAC Regarding Whether to Include
Certain Bulk Drug Substances on the 503A Bulk List

1. FDA is proposing that chrysin NOT be placed on the list of bulk drug substances
that can be used in pharmacy compounding in accordance with section 503A of
the FD&C Act (“the 503A bulk list”). Should chrysin be placed on the list?
2. FDA is proposing that cesium chloride NOT be placed on the 503A bulk list.
Should cesium chloride be placed on the list?
3. FDA is proposing that sodium dichloroacetate NOT be placed on the 503A bulk
list. Should sodium dichloroacetate be placed on the list?
________________________________________________________________________

B. June 23, 2016, p.m. session

Draft points to consider for the PCAC Regarding Whether to Include
Certain Bulk Drug Substances on the 503A Bulk List

1. FDA is proposing that pyruvic acid for topical use be INCLUDED on the 503A
bulk list. Should pyruvic acid for topical use be placed on the list?
2. FDA is proposing that tea tree oil NOT be placed on the 503A bulk list. Should
tea tree oil be placed on the list?
3. FDA is proposing that 2, 3-dimercapto-1-propanesulfonic acid (DMPS) NOT be
placed on the 503A bulk list. Should DMPS be placed on the list?

FDA Briefing Document Page 7
June 23, 2016
Tab 1

Chrysin
Tab 1a

Chrysin Nominations
Division of Dockets Management (HFA-305)
Food and Drug Administration
Department of Health and Human Services
5630 Fishers Lane
Rm. 1061
Rockville, MD 20852

Re: Docket FDA-2013-N-1525

“List of Bulk Drug Substances That May Be Used in Pharmacy Compounding; Bulk Drug Substances
That May Be Used To Compound Drug Products in Accordance With Section 503A of the Federal Food,
Drug, and Cosmetic Act”

Dear Sir or Madam,

Fagron appreciates the opportunity to address the FDA’s request for nominations of bulk drug substances that
may be used to compound drug products that are neither the subject of a United States Pharmacopeia (USP) or
National Formulary (NF) monograph nor components of FDA-approved drugs.

We hereby nominate the bulk drug substances in the attached spreadsheets for FDA’s consideration as bulk
drug substances that may be used in pharmacy compounding under Section 503A.

None of these items appear on an FDA-published list of drugs that present demonstrable difficulties for
compounding. In addition, none are a component of a drug product that has been withdrawn or removed from
the market because the drug or components of the drug have been found to be unsafe or not effective.

We include references in support of this nomination for your consideration.

Thank you for your consideration. If Fagron can answer any questions, please contact me ([email protected];
847-207-6100).

Respectfully submitted,

Julie Letwat, JD, MPH
Vice-President, Regulatory and Government Affairs

fa gron.us Fagron - 2400 Pilot Knob Road - St. Paul, MN 55120 - Tel. [phone] - Fax [phone]