The FDA’s Enforcement of Section 503B of the Federal Food, Drug, and Cosmetic Act


  • December 16, 2015

By Paul Eichholz

The FDA publishes weekly enforcement reports highlighting drugs that have been recalled during the previous week. Over the past several months these reports have been littered with hundreds of recalls by Compounding Pharmacies, claiming that their products are lacking sterility. This is a direct result of the FDA’s on-going enforcement activities of registered outsourcing facilities per Section 503B of the Federal Food, Drug, and Cosmetic Act.

A Compounding Pharmacy voluntarily registers as a 503B facility. As such, why are so many being cited by the FDA with significant FDA 483 Observations and subsequent Warning Letters? Is there still a general lack of understanding of the FDA’s expectations? Perhaps, but given the information that is readily available on FDA’s website, there should not be any surprises.

What Constitutes a 503B Outsourced Facility?

The Drug Quality and Security Act (DQSA) was enacted on November 27, 2013. Title I of the DQSA, the Compounding Quality Act (CQA), added a new section 503B to the FDCA. Section 503B(b) of the act states that a compounder can register as an outsourcing facility with FDA. If a drug product is compounded by (or under the direct supervision of) a licensed pharmacist in an outsourcing facility, and it meets the conditions in section 503B, it may qualify for exemptions from certain approval requirements, including:

An outsourcing facility is a facility at one geographic location or address that — (i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other provisions of the FDCA, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding unsanitary conditions. Generally, cGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211. It is critical to note that in essence, with a few exceptions the FDA expects an outsourced facility to meet the same GMP requirements that any manufacturer of a sterile drug is expected to meet. Additionally, failure to do abide by these requirements will lead to the same type of enforcement activities that a manufacturer would receive.

Challenges in Meeting FDA Requirements for Outsourced Facilities

A review of the FDA’s website quickly reveals an extensive list of challenges facing outsourcing facilities. The overwhelming majority of FDA enforcement actions involve significant FDA 483 Observations, followed in most cases by a Warning Letter after the FDA receives what they consider an incomplete or inadequate response to the initial FDA 483. In addition, a recall of all sterile products compounded by the firm typically occurs as well.

The most common observations noted by the FDA when inspecting outsourcing facilities includes (but is not limited to):

  • The outsourced facility failed to establish an adequate system for maintaining equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).
  • The outsourced facility failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).
  • The outsourced facility failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).
  • The outsourced facility failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
  • The outsourced facility failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).
  • The outsourced facility did not have, for each batch of drug product purporting to be sterile and/or pyrogen-free, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product (21 CFR 211.167(a)).

Outsourcing facilities are also failing to meet specific requirements regarding labeling and product lists, which, according to section 503B, are to be provided to the FDA every six months. Labeling of products compounded in an outsourced facility must provide clear directions on use, include the statements, “This is a compounded drug” and it is “Not for Resale,” and provide information on how to report adverse events.

Preventing or Addressing FDA Enforcement Activity

To prevent the FDA from taking enforcement actions against your firm there are several steps that should be taken before registering as a 503B facility. We can help evaluate your facilities, processes, equipment, training, laboratory, quality systems, and quality control. After all deficiencies noted have been addressed, you should verify the effectiveness of those activities.

If you have already registered as a 503B facility, or have been subjected to FDA enforcement actions, all is not lost. We can still help. We have significant experience assisting in the development of responses to the FDA’s actions. We can work with you, taking swift and appropriate action for sterile compounded drugs already in distribution, correcting all deficiencies in a thorough and expeditious manner, and always verifying the effectiveness of those activities.

For information on how The Weinberg Group can assist your organization in addressing 503B compliance, contact us today.

Paul Eichholz, is Senior Vice President, Quality & Compliance at The Weinberg Group, the world’s leading food and drug consulting firm. If you have any questions or thoughts on this blog post or others, please do not hesitate to contact us.