On April 15, 2016, the U.S. Food and Drug Administration (FDA) announced the release of three new draft guidance documents on drug compounding under Sections 503A and 503B of the Food, Drug, and Cosmetic Act (FDCA).[1] These draft guidance documents cover:

Through these topics, the documents provide further insight into FDA’s current position on certain areas of drug compounding.

Prescription Requirement Under Section 503A

In its draft guidance on Section 503A’s prescription requirement, FDA provided insight into its approach to enforcement of Section 503A’s requirement that compounding eligible for certain FDCA exemptions under 503A may occur only pursuant to a valid prescription or under very limited circumstances prior to receipt of such a prescription. While FDA acknowledged the need for some physicians to maintain office supplies of compounded drugs, it established a relatively strict approach to anticipatory compounding, including compounding for office use. FDA noted that under Section 503A(a)(2) of the FDCA, licensed pharmacists and physicians may compound prior to receipt of a patient-specific prescription only if such compounding is in limited quantity and based on a history of receiving valid prescription orders for the compounded drug within the context of an established relationship with the prescribing practitioner.

FDA declared that it would not “consider a compounder to have exceeded the limited quantity condition” as long as it holds no more than a 30-day supply of a particular compounded drug in order to fill valid prescriptions it receives later. The compounder must determine what constitutes a 30-day supply based on the maximum amount of a given product for which it received patient-specific prescriptions in a 30-day period during the previous year. If these requirements are met, FDA will not try to determine whether the compounder actually expected to receive a prescription for a particular patient or prescriber prior to compounding the drug product. However, FDA stated that if a hospital, clinic or other medical office wishes to store compounded products in excess of the limited quantities described above, it must obtain such compounded drugs from a registered outsourcing facility compliant with Section 503B.

Hospital and Health System Compounding

In its draft guidance on hospital and health system compounding, FDA recognized the need of hospitals to maintain supplies of certain compounded drugs in anticipation of immediate patient needs, but reiterated that compounding under Section 503A requires a patient-specific prescription. Nonetheless, FDA stated that it does not intend to take enforcement actions against hospital pharmacies that distribute compounded drugs without a patient-specific prescription, provided that all of the following conditions are met:

  1. The hospital pharmacy distributes the compounded products only to facilities under common ownership and control and that are located within one mile of the compounding pharmacy;
  2. The drugs will be administered only within the health facility, pursuant to a patient-specific prescription; and
  3. The pharmacy otherwise complies with all of the requirements of Section 503A in compounding the drug.

If a hospital system wishes to have one pharmacy distribute compounded drugs without a patient prescription to affiliated hospitals and practices beyond the one-mile radius, the pharmacy must register with FDA as an outsourcing facility. Thus, FDA’s new draft guidance tightly limits the ability of large hospital systems to centralize their compounding activities without being required to register with FDA and comply with the requirements of 503B.

Facility Definition Under Section 503B of the FDCA

Section 503B of the FDCA created a new category of compounding facilities called outsourcing facilities. Registered outsourcing facilities, defined in part as “a facility at one geographic location or address,” may compound drugs without patient prescriptions while also qualifying for exemptions from the FDCA’s new drug approval and adequate directions for use labeling requirements. Such facilities must, however, comply with certain current Good Manufacturing Practice (cGMP) requirements.[2] The recently released draft guidance clarifies FDA’s understanding of “facility” under Section 503B and its position on whether a registered 503B outsourcing facility may also conduct other types of compounding activities in separate areas of the same premises.

As discussed in an earlier Duane Morris Alert, FDA has previously explained that a facility should register as an outsourcing facility only if all of its compounded drugs will be compounded in compliance with Section 503B. In the new draft guidance, FDA explains that it “considers all activities, equipment, appurtenances, and materials part of a [facility at one geographic location or address] if they are related to human drug compounding under the supervision of the facility’s management at the same street address, or in the same building, or in buildings located in close proximity to one another.” Thus, although an outsourcing facility can compound pursuant to a patient prescription, it cannot also compound drugs under Section 503A of the FDCA[3]even if the areas devoted to the two standards for compounding are segregated from one another. Among FDA’s concerns are that housing 503A and 503B compounding activities in the same building or facility could lead to the appearance that all drugs compounding at the facility comply with the purportedly higher standards of Section 503B, that comingling of products and activities could lead to confusion as to which standards apply and that it may be impossible to distinguish between the drugs compounded under 503A and those compounded under 503B.

In contrast, FDA will allow compounding under Section 503B to occur at a facility that also engages in “conventional” drug manufacturing because all activities at such facilities would be required to comply with cGMPs. Further, it is much easier to distinguish between compounded and manufactured drugs because of differing approval and labeling requirements, such as the requirement that compounded drug labels include the statement: “This is a compounded drug.”

Conclusion

FDA is accepting public comments on the three draft guidance documents through July 18, 2016.[4] Comments may be submitted electronically at http://www.regulations.gov or in writing to the FDA Division of Dockets Management. Further details on the procedure for submitting comments on the respective draft guidance documents are provided in the Federal Register as part of FDA’s notice for each document.[5] Stakeholders with concerns about FDA’s newly asserted positions should consider submitting comments to FDA.