An overview of FDA’s 503B outsourcing facility requirements

August 10, 2016

FDA has stated that it intends to continue inspections of compounding pharmacies, and it has taken aggressive action, including enforcement actions, as appropriate to protect the public health.

Ned MilenkovichThe 2013 Compounding Quality Act passed by Congress provides a pathway for a pharmacy acting as a Section 503B “outsourcing facility” to register as such with the FDA. Once registered, an outsourcing facility must meet specific conditions to be exempt from the Food, Drug & Cosmetics Act’s (FDCA) approval requirements and product labeling requirements.

The law requires that drugs be compounded in compliance with CGMPs either by or under the direct supervision of a licensed pharmacist in a registered facility. Information on the products compounded at the facility must be reported, to include a list of all products compounded during the previous six months and details about the compounded products, such as source of ingredients used. Other conditions must also be met under the law including reporting adverse events and labeling products with prescribed information.

An outsourcing facility will not be considered registered until it has paid its annual registration fee. In addition, the law requires that outsourcing facilities register and report their products to FDA electronically.

Traditional pharmacy compounding

Drugs produced by pharmacy compounders that are not registered as outsourcing facilities must meet the conditions of section 503A to qualify for the specified exemptions. Except for the limited exemptions, all other applicable provisions of the FDCA remain in effect for compounded drugs, even if the conditions in section 503A are met.

FDA’s intention with regard to FDCA Section 503a is described in a draft guidance document issued by the agency. Also described in this draft guidance are the provisions of the law that can be applied to compounded drugs that do not qualify for exemptions, and the other provisions of the FDCA applicable to compounded drugs whether or not they qualify for the exemptions under Section 503A. FDA also withdrew CPG 460.200 Pharmacy Compounding, issued in 2002, and the guidance Enforcement Policy During Implementation of Section 503A of the Federal Food, Drug, and Cosmetic Act, published in November 1998.

   Board of Pharmacy Interface
 

The Compounding Quality Act requires FDA to obtain submissions from state boards of pharmacy concerning certain actions taken against compounding pharmacies or expressing concerns that a facility may be acting contrary to Section 503A. State boards of pharmacy also must be notified when FDA receives certain submissions from the state or makes a determination that a compounding pharmacy is acting contrary to section 503A.

 

 

Nominations for Lists

In sections 503A and 503B are included various requirements for FDA to develop lists of drugs that may or may not be compounded and lists of bulk drug substances that may be used in compounding. Section 503A specifies that to qualify for the exemptions under section 503A, a compounder may only use bulk drug substances to compound if:

The bulk drug substances comply with the standards of an applicable United States Pharmacopoeia or National Formulary monograph, if one exists;

If such a monograph does not exist, the drug substance(s) is a component of an FDA-approved human drug product; or

If such a monograph does not exist and the drug substance is not a component of an FDA-approved human drug product, it appears on a list of bulk drug substances for use in compounding developed by FDA.

Under section 503B, a registered outsourcing facility may only use for compounding a bulk drug substance that is included on an FDA-established list of bulk drug substances for which there is a clinical need or which are on FDA’s drug shortage list. Prohibited under sections 503A and 503B is the compounding of drugs that are on a list of drugs that present difficulties for compounding.

Inspections and Enforcement

FDA has stated that it intends to continue inspections of compounding pharmacies, and has taken aggressive action, including enforcement actions, as appropriate to protect the public health. In many cases, Form FDA-483’s were issued accompanied by recalls of sterile products.