FDA continues to issue guidance on how to enforce the Drug Quality and Security Act after the compounding law was enacted in late 2013.

The agency released four new draft guidance documents on February 13 related to the manufacture and distribution of compounded drugs. Two of them pertain to 503B outsourcing facilities. The other two, applicable to both 503A pharmacies and 503B outsourcing facilities, address repackaging both generally and for biologics. FDA told stakeholders they have 90 days—until May 13, 2015—to comment on the draft guidance.

FDA released these guidance documents along with a draft memorandum of understanding (MOU), which seeks to establish an agreement between states and FDA about interstate distribution of compounded drug products. Since MOU negotiations tend to be more timely and involved, FDA is giving stakeholders until June 13, 2015—120 days—to comment.

Jillanne Schulte, JD, APhA Director of Regulatory Affairs, said a few provisions in the MOU draft stick out. Of immediate concern is language that sets strict limits on the amount of drug product that can be distributed interstate. If pharmacies distribute an “inordinate amount” of compounded drug product interstate, they can lose 503A protection and are subject to state and FDA investigation.  FDA defines “inordinate amount” for states that have entered into the MOU as “an amount of compounded drug product distributed interstate in a given month that is equal or greater to 30% of all drug products dispensed or distributed by the pharmacist, pharmacy, or physician.” The draft MOU requires states to report distribution of “inordinate amounts” of compounded drug products to FDA.

The MOU also does not include an exemption for border states, such as New York and New Jersey, to distribute compounded drug products, nor does it include safeguards for drug shortages, further narrowing permissible interstate distribution.

Schulte said the MOU will not be effective until well after the end of the comment period, as the FDA will need to make any necessary changes and provide at least 180 days for states to determine whether to sign the MOU.

Following are hyperlinks to the four new draft guidance documents as well as the draft MOU:

• For Entities Considering Whether to Register As Outsourcing Facilities Under Section 503B of the FDCA
• Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the FDCA
• Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities
• Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application
• Memorandum of Understanding (MOU)

APhA members should e-mail Jillanne Schulte with any comments they would like to see included in the Association’s comments.

Compliant facilities

The Drug Quality and Security Act created a new section 503B of the Federal Food, Drug, and Cosmetic Act. Section 503B defines an outsourcing facility as an entity that engages in compounding of sterile drugs that has elected to register as an outsourcing facility.

In follow-up to previous guidance regarding registration as an outsourcing facility, the new guidance lays out considerations for pharmacies considering registration under 503B. FDA has repeatedly stated that it will not opine on whether specific pharmacies should register under 503B, so the guidance functions as a self-evaluation tool for pharmacies, according to Schulte. The guidance notes that all drugs, including sterile compounds, nonsterile compounds, and any patient-specific prescriptions compounded by a 503B facility, will be subject to FDA inspection and oversight. FDA states that an entity that compounds and distributes only nonsterile medications will not qualify as an outsourcing facility. The facility must compound some sterile human medications (purely veterinary compounders cannot register), although a qualifying amount is not specified. Additionally, the drugs prepared by the facility must follow current Good Manufacturing Practices and establish an adverse event reporting system process.

FDA included draft guidance specific to adverse event reporting for 503B facilities too. FDA states that all facilities must report all serious and unexpected adverse events to the agency within 15 days with the name of the drug and the suspected adverse event. In the report, FDA asks that labeling information be included and an attempt be made to find out certain information associated with the patients who reported the suspected adverse event.

Repackaging rules

FDA’s draft guidance on repackaging certain human drugs by pharmacies and outsourcing facilities explicitly states that it does not consider repackaging to be compounding—and the exemptions for both 503A or 503B do not apply. FDA said repackaging may be permitted when it occurs in a pharmacy, federal facility, or 503B outsourcing facility, and when it is done under the direct supervision of a pharmacist.

The other repackaging guidance from FDA concerns biologics, and also addresses mixing and diluting biologic products when they are not consistent with FDA-approved labeling. FDA said a pharmacy may repackage a biologic in advance of receiving a prescription, but can only dispense the product based upon receipt of either the individual patient prescription or the written order in the patient’s chart.