Download IACP Comparison of 503A and 503B The Drug Quality and Security

IACP Comparison of 503A and 503B
The Drug Quality and Security Act of 2013
Exempt Sections
within the Food,
Drug, and
Cosmetic Act
Bulk Ingredients
Section 503A - Traditional Compounder
If a "traditional compounder", defined as a licensed pharmacist or
licensed physician, meets ALL conditions within Section 503A, the
compounder is exempt from THREE sections within the Food, Drug,
and Cosmetic Act; (1) Section 501(a)(2) (concerning current good
manufacturing practices); (2) Section 502(f)(1) (concerning labeling
or drugs with adequate directions for use); and (3) Section 505
(concerning the approval of drugs under new drug applications or
abbreviated new drug applications).
Section 503B - Outsourcing Facility
If a facility meets ALL conditions within Section 503B, the
outsourcing facility is exempt from TWO sections within the Food,
Drug, and Cosmetic Act: (1) Section 502(f)(1) (concerning
labeling of drugs with adequate directions for use): and (2) Section
505 (concerning the approval of human drug products under new
drug applications (NDAs) or (ANDAs).
Section 503A - Traditional Compounder
A drug product may be compounded if the licensed pharmacist or
licensed physician if they
(A) compounds the drug product using bulk drug substances, as
defined in regulations of the Secretary published at section
207.3(a)(4) of title 21 of the Code of Federal Regulations— (i) that
- comply with the standards of an applicable United States
Pharmacopoeia or National Formulary monograph, if a monograph
exists, and the United States Pharmacopoeia chapter on pharmacy
compounding; OR
- if such a monograph does not exist, are drug substances that are
components of drugs approved by the Secretary; OR
- if such a monograph does not exist and the drug substance is
not a component of a drug approved by the Secretary, that appear on
a list developed by the Secretary through regulations issued by the
Secretary under subsection (d) of this section; AND
- that are manufactured by an establishment that is registered
under section 360 of this title (including a foreign establishment that
is registered under section 360(i) of this title); AND
- that are accompanied by valid certificates of analysis for each
bulk drug substance.
Section 503B - Outsourcing Facility
If a facility chooses to register with the FDA , the facility must
comply with the following requirements regarding bulk drug
substances:
- The drug is compounded in an outsourcing facility that does not
compound using bulk drug substances unless: (1) the bulk drug
substance appears on a list established by the Secretary OR (2) the
drug compounded from bulk drug substances appears on the drug
shortage list; AND
- Where an applicable monograph exists under USP, the National
Formulary, or another compendium or pharmacopeia recognized
by FDA, the bulk drug substances each comply with the
monograph; AND
- The bulk drug substances are each manufactured by an
establishment recognized under section 510; AND
- The bulk drug substances are each accompanied by a valid
certificate of analysis.
**FDA is currently soliciting nominations for this list.
Nominations are due to the FDA no later than 4 March 2014.
**FDA previously published a proposed rule listing bulk drug
substances that may be used in pharmacy compounding. FDA
intends to reconsider the bulk drug substances that were
proposed for inclusion on the list and seek additional
nominations and propose. Nominations are due to the FDA no
later than 4 March 2014.
Ingredients other
than Bulk
Ingredients
Section 503A - Traditional Compounder
Section 503B - Outsourcing Facility
Compounds the drug product using ingredients (other than bulk drug Ingredients must comply with standards of USP or National
substances) that comply with the standards of an applicable United
formulary monograph if such monograph exists, or another
States Pharmacopoeia or National Formulary monograph, if a
compendium or pharmacopeia recognized by FDA.
monograph exists, and the United States Pharmacopoeia chapter on
pharmacy compounding; The Secretary, in consultation with the
United States Pharmacopoeia Convention, shall promulgate
regulations identifying drug substances that may be used in
compounding under subsection (b)(1)(A)(i)(III) of this section for
which a monograph does not exist or which are not components of
drug products approved by the Secretary. The Secretary shall
include in the regulation the criteria for such substances, which shall
include historical use, reports in peer reviewed medical literature, or
other criteria the Secretary may identify.
(c) 2014. International Academy of Compounding Pharmacists. All Rights Reserved.
Page 1 of 6
IACP Comparison of 503A and 503B
The Drug Quality and Security Act of 2013
Withdrawn or
Removed from
Market - Do Not
Compound List
Commercially
Available
Section 503A - Traditional Compounder
Shall not compound a drug product that appears on a list published
by the Secretary in the Federal Register of drug products that have
been withdrawn or removed from the "Shall not compound a drug
product that appears on a list published by the Secretary in the
Federal Register of drug products that have been withdrawn or
removed from the market because such drug products or components
of such drug products have been found to be unsafe or not effective.
**FDA promulgated a Final Rule codified at 21 CFR 216.24,
which lists drug products that may not be compounded because
they have been withdrawn or removed from the market because
the drug products or components of the drug products were
found to be unsafe. Until the previously published list is
updated, all traditional compounders are expected to follow the
list published in 2002.
Section 503B - Outsourcing Facility
The Secretary has authority to include drugs on a list that cannot
be compounded of drugs that have been withdrawn or removed
from the market because such drugs or components of such drugs
have been found to be unsafe or not effective.
Section 503A - Traditional Compounder
Shall not compound regularly or in inordinate amounts (as defined
by the Secretary) any drug products that are essentially copies of a
commercially available drug product.
For purposes of this Section, the term “essentially a copy of a
commercially available drug product” does not include a drug
product in which there is a change, made for an identified individual
patient, which produces for that patient a significant difference, as
determined by the prescribing practitioner, between the compounded
drug and the comparable commercially available drug product.
Section 503B - Outsourcing Facility
The drug shall not be essentially a copy of one or more approved
drugs.
For this Section, essentially a copy of an approved drug" means -‘‘(A) a drug that is identical or nearly identical to an approved
drug, or a marketed drug not subject to section 503B and not
subject to approval in an application submitted under section 505,
unless, in the case of an approved drug, the drug appears on the
drug shortage list in effect under section 506E at the time of
compounding, distribution, and dispensing; OR ‘‘(B) a drug, a
component of which is a bulk drug substance that is a component
of an approved drug or a marketed drug that is not subject to
section 503B and not subject to approval in an application
submitted under section 505, unless there is a change that produces
for an individual patient a clinical difference, as determined by the
prescribing practitioner, between the compounded drug and the
comparable approved drug.
For this Section, the term "approved drug" means -- a drug that is
approved under section 505 and does not appear on the list
described in subsection (a)(4) of drugs that have been withdrawn
or removed from the market because such drugs or components of
such drugs have been found to be unsafe or not effective.
(c) 2014. International Academy of Compounding Pharmacists. All Rights Reserved.
Page 2 of 6
IACP Comparison of 503A and 503B
The Drug Quality and Security Act of 2013
Demonstrable
Difficulties - Do
Not Compound
List
Risk Evaluation
and Mitigation
Strategy (REMS)
Prohibition on
Wholesaling
Section 503A - Traditional Compouner
A drug product may be compounded only if— such drug product is
not a drug product identified by the Secretary by regulation as a
drug product that presents demonstrable difficulties for
compounding that reasonably demonstrate an adverse effect on the
safety or effectiveness of that drug product.
**This provision is not enforceable until FDA promulgates an
implementing regulation. FDA is seeking nominations of
"demonstrably difficult" drugs or drug classes for review and
evaluation by the Pharmacy Compounding Advisory Committee.
Section 503B - Outsourcing Facility
The drug can be compounded if it's not identified on a do not
compound list by FDA through the regulatory process. The list
can include drugs or categories of drugs that present demonstrable
difficulties for compounding that are reasonably likely to lead to
an adverse effect on the safety or effectiveness of the drug or
category of drugs, taking into account the risks and benefits to the
patients; OR
Is compounded in accordance with all applicable conditions
identified on the list by FDA as conditions that are necessary to
prevent the drug or category of drugs from presenting
demonstrable difficulties. This list must be developed through the
regulatory process AND before issuing regulations, FDA must
convene and consult an advisory committee on compounding. The
advisory committee must include representatives from NABP,
USP, the US Pharmacopeia, pharmacists with current experience
and expertise in compounding, physicians with background and
knowledge in compounding, and patient and public health
advocacy organizations.
Section 503A - Traditional Compounder
No language addresses the compounding of drug products which are
currently subject to a REMS program.
Section 503B - Outsourcing Facility
In the case of a drug that is compounded from a drug that is
subject to a risk evaluation and mitigation strategy approved with
elements to assure safe use or from a bulk drug substance that is a
component of such drug, the outsourcing facility must demonstrate
to FDA prior to beginning compounding that such facility will
utilize controls comparable to the controls applicable under the
relevant REMS.
Section 503A - Traditional Compounder
No language addresses wholesaling within 503A - however, state
wholesaling language may be applicable.
Section 503B - Outsourcing Facility
The drug cannot be sold or transferred by an entity other than the
outsourcing facility that compounded such drug. This section does
not prohibit office use and the administration of a drug in a health
care setting or dispensing a drug pursuant to a prescription.
(c) 2014. International Academy of Compounding Pharmacists. All Rights Reserved.
Page 3 of 6
IACP Comparison of 503A and 503B
The Drug Quality and Security Act of 2013
Labeling
Registration
Requirements
Section 503A - Traditional Compounder
No label requirements within 503A.
Section 503B - Outsourcing Facility
Compounded medications must be labeled with the following:
-This is a compounded drug or a reasonable comparable
alternative statement;
- The name, address, and phone number of the applicable
outsourcing facility;
- With respect to the drug -- the lot or batch number, the
established name of drug, the dosage form and strength, the
statement of quantity or volume, the date that the drug was
compounded, the expiration date, the storage and handling
instructions, the National Drug Code number, the statement “not
for resale” or “office Use only” where applicable, and a list of
active and inactive ingredients identified by established name and
the quantity or proportion of each ingredient.
- With respect to the container – the container from which
individual units are removed for dispensing or for administration
shall include: a list of active and inactive ingredients, identified by
established name and quantity or proportion of each ingredient
where there is no space on the label, information to facilitate
adverse event reporting, and directions for use, including as
appropriate dosage and administration.
- In addition, any other information determined necessary by FDA
through a regulatory process must be included on the label.
Section 503A - Traditional Compounder
None within 503A.
Section 503B - Outsourcing Facility
When a facility chooses to register with the FDA, the registration
must occur on an annual basis between October 1 and December
31. The facility must register its name, place of business, and
unique facility identifier and a point of contact email address. The
facility shall indicate whether the outsourcing facility intends to
compound a drug that appears on the drug shortages list during the
subsequent calendar year. FDA must make this registration
information available to the public and post a list on the FDA’s
website of the name of each facility registered as an outsourcing
facility, the State in which each facility is located, whether the
facility compounds from bulk drug substances, and whether any
such compounding bulk drug substances is for sterile or non-sterile
drugs.
**FDA recently released proposed guidance regarding 503B
registration and is currently soliciting comments. In terms of
interim registration, FDA encouraged facilities to use FDA's
electronic registration system but since this is a new
requirement, FDA is proposing to allow outsourcing facilities
that register to register under an alternative interim
registration by submitting required information in an email to
[email protected]. FDA encourages OFs to begin using this
alternative method no later than September 30, 2014. *** An
OF can currently register without paying a fee until October 1,
2014.
(c) 2014. International Academy of Compounding Pharmacists. All Rights Reserved.
Page 4 of 6
IACP Comparison of 503A and 503B
The Drug Quality and Security Act of 2013
Reporting
Requirements
Section 503A - Traditional Compounder
None within 503A.
Section 503B - Outsourcing Facility
After voluntarily registering with the FDA, the outsourcing facility
during June and December of each year must submit a report to
FDA.
The report must:
- Identify the dugs compounded by such outsourcing facility
during the previous 6 months; and
- For each drug – provide the active ingredient, source of active
ingredient, the National Drug Code number of the source drug or
bulk active ingredient, if available, the strength of the active
ingredient per unit, the dosage form and route of administration,
the package description, the number of units produced, and the
National Drug Code number of the final product, if assigned.
** FDA recently released interim reporting guidance and is
soliciting comments. ***In order to encourage facilities to
register and report with FDA, if a facility register before June
2, 2014, FDA does NOT intend to immediately enforce the
requirement to report product information at the time of initial
registration, as long as the facility submits its report within 2
months after the date of that initial registration.
Section 503A - Traditional Compounder
Advisory
Committee
Fees
Before issuing regulations to implement subsections on BULK
DRUG SUBSTANCES, DO NOT COMPOUND LIST FOR
REMOVED OR WITHDRAWN FROM MARKET, or DO NOT
COMPOUND LIST FOR DEMONSTRABLY DIFFICULTY, the
Secretary shall convene and consult an advisory committee on
compounding unless the Secretary determines that the issuance of
such regulations before consultation is necessary to protect the
public health. The advisory committee shall include representatives
from the National Association of Boards of Pharmacy, the United
States Pharmacopoeia, pharmacy, physician, and consumer
organizations, and other experts selected by the Secretary.
Section 503A - Traditional Compounder
None within 503A.
Section 503B - Outsourcing Facility
The BULK DRUG SUBSTANCES and DEMONSTRABLY
DIFFICULT do not compound list must be developed through the
regulatory process AND before issuing regulations on
DEMONSTRABLY DIFFICULT, FDA must convene and
consult an advisory committee on compounding. The advisory
committee must include representatives from NABP, USP, the US
Pharmacopeia, pharmacists with current experience and expertise
in compounding, physicians with background and knowledge in
compounding, and patient and public health advocacy
organizations.
Section 503B - Outsourcing Facility
Beginning in 2015 and on an annual basis, outsourcing facilities
must pay annual establishment fees as well as reinspection fees. In
addition, if an outsourcing facility chooses to continue to practice
as a pharmacy, the outsourcing facility is also responsible for all
fees owed to the state Boards of Pharmacy.
Fee amounts will be published not later than 60 calendar days
before the start of each year.
Amount of the annual establishment fee will be $15,000
multiplied by the inflation adjustment factor. The amount of any
reinspection fee will be equal to $15,000 multiplied by the
inflation adjustment factor.
Reduced Fee for Small Businesses – Number of small business
that will pay a reduced amount for the establishment fee will be
determined by the Secretary. An outsourcing facility with gross
annual sales of $1 million or less in the 12 months ending April 1
of the fiscal year preceding the fiscal year in which fees are due,
shall pay 1/3 the amount of the establishment fee for a non-exempt
outsourcing facility.
(c) 2014. International Academy of Compounding Pharmacists. All Rights Reserved.
Page 5 of 6
IACP Comparison of 503A and 503B
The Drug Quality and Security Act of 2013
Shipping
Restrictions
Section 503A - Traditional Compounder
The drug product must be compounded in a State—
(i) that has entered into a memorandum of understanding with the
Secretary which 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 State; OR
(ii) that has not entered into the memorandum of understanding
described in clause (i) and the licensed pharmacist, licensed
pharmacy, or licensed physician distributes (or causes to be
distributed) compounded drug products out of the State in which
they are compounded in quantities that do not exceed 5 percent of
the total prescription orders dispensed or distributed by such
pharmacy or physician.
The Secretary shall, in consultation with the National Association of
Boards of Pharmacy, develop a standard memorandum of
understanding for use by the States.
Section 503B - Outsourcing Facility
None within 503B
**FDA is currently drafting the MOU and recently announced
that FDA does not intend to enforce the 5% limit on interstate
distribution until 90 days after FDA has finalized an MOU and
made it available to the States for their consideration and
signature.
For the
Administration in
a Health Facility Office Use
Section 503A - Traditional Compounder
Language within 503A states that a "drug product is compounded
for an identified individual patient." No reference to "office use"
compounding appears in 503A.
(c) 2014. International Academy of Compounding Pharmacists. All Rights Reserved.
Section 503B - Outsourcing Facility
An 503B may or may not obtain prescriptions for identified
individual patients. Thus, office-use is allowed.
Page 6 of 6