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Editorial: FDA Guidance Under 503a
This week we will look at a summary of the recently issued (December 2013) FDA Draft Guidance concerning Section 503A regarding traditional compounding. Only selected portions are presented here. Next week we will look at the Guidance for Section 503B.
For a full copy of the Guidance and how to respond, go to:
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/
guidances/ucm377052.pdf
I. INTRODUCTION
This guidance announces FDA's intention with regard to enforcement of section 503A to regulate entities that compound drugs, now that section 503A has been amended by Congress to remove the advertising and solicitation provisions that were struck down as unconstitutional by the U.S. Supreme Court in 2002. Several parts of section 503A require rulemaking and consultation with a Pharmacy Compounding Advisory Committee to implement. This guidance explains how those provisions will be applied pending those consultations and rulemaking. This guidance also describes some of the possible enforcement actions FDA may bring against individuals or firms that compound drugs in violation of the FD&C Act.
This guidance does not apply to registered outsourcing facilities under section 503B of the FD&C Act. Guidance for outsourcing facilities will be issued separately.
===THE LAW===
III. POLICY
A drug product intended for use in humans that is compounded in compliance with section 503A and its associated regulations is exempt from the requirements in sections 501(a)(2)(B), 502(f)(1), and 505 of the FD&C Act. All other applicable provisions of the FD&C Act remain in effect for compounded drugs, however, even if the conditions of section 503A are met.
FDA expects State boards of pharmacy to continue their oversight and regulation of the practice of pharmacy, including traditional pharmacy compounding. FDA also intends to continue to cooperate with State authorities to address pharmacy activities that may be violative of the FD&C Act, including section 503A. FDA's enforcement approach with respect to such violations is described below.
A. Conditions of Section 503A
Under section 503A of the FD&C Act, a compounded drug product is exempt if it meets the conditions of section 503A of the FD&C Act. Specifically, the compounded drug product qualifies for the exemptions if:
1. The drug product is 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.
2. The compounding of the drug product is performed:
• By a licensed pharmacist in a State licensed pharmacy or a Federal facility, or by a licensed physician on the prescription order for an individual patient made by a licensed physician or other licensed practitioner authorized by State law to prescribe drugs; or
• By a licensed pharmacist or licensed physician in limited quantities before the receipt of a valid prescription order for such individual patient when:
- the licensed pharmacist or licensed physician has historically received valid prescription orders for the compounding of the human drug product and
- the orders have been generated solely within an established relationship between the licensed pharmacist or licensed physician and either the patient for whom the prescription order will be provided or the physician or other licensed practitioner who will write such prescription order.
3. The drug product is compounded in compliance with the United States Pharmacopoeia (USP) chapters on pharmacy compounding using bulk drug substances that comply with the standards of an applicable USP or National Formulary (NF) monograph, if one exists.
If such a monograph does not exist, the drug substance(s) must be a component of an FDA-approved human drug product. If a monograph does not exist and the drug substance is not a component of an FDA-approved human drug product, it must appear on a list of bulk drug substances for use in compounding developed by FDA through regulation.
4. The drug product is compounded using bulk drug substances that are manufactured by an establishment that is registered (including a foreign establishment).
5. The drug product is compounded using bulk drug substances that are accompanied by valid certificates of analysis for each bulk drug substance.
6. The drug product is compounded using ingredients (other than bulk drug substances) that comply with the standards of an applicable USP or NF monograph, if one exists, and the USP chapters on pharmacy compounding.
7. The drug product does not appear on the list that includes 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.
8. The licensed pharmacist or licensed physician does not compound regularly or in inordinate amounts any drug products that are essentially copies of commercially available drug products.
9. The drug product is not a drug product identified by FDA 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.
10. The drug product is compounded in a State that has entered into a memorandum of understanding (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 State; or in States that have not entered into such an MOU with FDA, the licensed pharmacist, licensed pharmacy, or licensed physician does not distribute, or cause to be distributed, compounded drug products out of the State in which they are compounded, more than 5% of the total prescription orders dispensed or distributed by such pharmacy or physician.
====ACTIONS====
B. Provisions of Section 503A That Require Regulations or Other FDA Actions
Specific sections of 503A of the FD&C Act require rulemaking or other action by FDA. FDA's policy related to these specific sections is described below.
1. Withdrawn or Removed List
FDA promulgated a final rule 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 have been found to be unsafe or not effective. FDA intends to update this list periodically, and expects compounders to comply with the list as it currently exists and with any updates.
2. Bulk Drug Substances List
Section 503A provides that a drug product may be compounded using bulk drug substances that do not have an applicable USP or NF monograph and are not components of FDA-approved drugs if the bulk drug substances appear on a list developed by FDA and issued through regulation.
Until a bulk drug substances list is published in the Federal Register as a final rule, human drug products should be compounded only using bulk drug substances that are components of drugs approved under section 505 of the FD&C Act, or are the subject of USP or NF monographs.
3. "Demonstrable Difficulties" for Compounding
A compounded drug product would not qualify for the exemptions if it is identified by FDA through regulation as a drug product that presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of the drug product. This provision is not enforceable until FDA promulgates an implementing regulation.
4. Memorandum of Understanding Between FDA and the States
Section 503A states that FDA, in consultation with the National Association of Boards of Pharmacy (NABP), will develop a standard MOU for use between FDA and the States that will address the interstate distribution of inordinate amounts of compounded drug products and provide for appropriate investigation by a State agency of complaints relating to compounded drug products distributed outside that State. On January 21, 1999, FDA published a notice in the Federal Register announcing the availability of a draft standard MOU, developed in consultation with the NABP. This draft MOU was not finalized. FDA intends to publish a new draft MOU for comment that will replace the January 1999 draft.
An individual or firm in a State that does not enter into an MOU with FDA that distributes, or causes to be distributed, compounded drug products out of the State in which they are compounded, can compound for interstate distribution outside the state only 5% of the total prescription orders dispensed or distributed by the individual or firm. 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.
====PENALTIES====
B. Enforcement Action When a Drug Does Not Meet the Conditions of Section 503A
If FDA determines that an individual or firm compounds a drug product that does not meet the conditions of section 503A, then in addition to the violations listed in section IV.A., the individual or firm that compounds the drug product may also be subject to a warning letter, seizure of product, injunction, and/or criminal prosecution for violations of sections 501(a)(2)(B), 502(f)(1), and 505 of the FD&C Act.
Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition
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