FDA is Issuing Proposed Regulations on CGMP Requirements for 503B Facilities and Publishing Revised Draft Guidance in the Interim Describing a New Flexible Risk-Based Approach to CGMP

FDA will issue proposed regulations on CGMP requirements for outsourcing facilities. In the short term, FDA is revising the draft guidance to describe a new flexible risk-based approach to CGMP requirements for 503B facilities. The draft revised guidance will:

• Consider how CGMP requirements are applied based on the operations of an outsourcing facility’s size and scope; and
• Describe the circumstances in which FDA does not intend to enforce certain CGMP requirements applicable to conventional drug manufacturers against 503B facilities.

FDA Issued Two Final Guidance Documents Restricting Compounding Drugs that are Essentially Copies of FDA-Approved Drugs

A component of the Federal Food, Drug and Cosmetic Act (FD&C Act) is the restrictions it places on compounding drugs that are essentially copies of FDA-approved or commercially available products. On January 19, 2018, FDA issued two final guidance documents regarding the copies provisions for 503A and 503B facilities. These documents define what FDA considers an essential copy of a FDA-approved or commercially available product.

These final guidances set out different criteria, as Section 503A and Section 503B have differing requirements regarding what are essentially copies of commercial available drugs. Drafts of both of these guidances were issued in July 2016 and submitted for public comment. The final guidances do reflect some revision and, therefore, pharmacies subject to this regulation should carefully review FDA’s current thinking on these issues.

As FDA moves toward implementation and enforcement of the restrictions in the FD&C Act on compounding copies, FDA intends to focus its efforts on education and outreach to practitioners, including prescribers of compounded drugs. FDA further intends to prioritize the review of situations that could adversely impact the public health and premarket approval process.

Regulating Compounding from Bulk Substances for 503A and 503B

As a temporary step, FDA issued interim policy guidelines to address compounding from bulk drug substances by 503A and 503B facilities while it developed the bulks lists. In December 2016, the agency proposed regulations to address 10 of these substances and establish the criteria FDA would use to evaluate the substances for inclusion on the list. After considering public comments, FDA intends to issue a final regulation in 2018. FDA will also continue to evaluate additional bulk drug substances that were nominated.

In March 2018, FDA plans to issue a draft guidance document that proposes criteria for making clinical need determination for purposes of establishing the 503B bulks list. FDA intends to address concerns about compounding from bulk drug substances when the drug can be compounded from FDA-approved drugs in this guidance. This draft guidance will provide health care clinicians, practitioners and compounding companies an opportunity to submit comments.

FDA Will Clarify Relationship with State Regulatory Authorities by Issuing a Revised Draft MOU Regarding Compounding Under 503A

After receiving more than 3,000 comments as well as congressional interest, FDA intends to issue a significantly revised draft MOU between FDA and states regarding compounding under section 503A. The former draft:

• Stated that if a pharmacy distributed an “inordinate amount” of compounded drugs interstate, the state would agree to take action.
• Defined an “inordinate amount” as “an amount of compounded drugs distributed interstate in a given month that is equal or greater to 30 percent of all drug products dispensed or distributed by the pharmacist, pharmacy, or physician.”

FDA anticipates that the revised MOU will state:

• That a compounder has distributed an inordinate amount of drugs interstate if the number of prescriptions of compounded drugs distributed interstate during any calendar month is greater than 50 percent; and
• The state boards are not required to act if a compounder distributes an “inordinate amount,” but instead, distribution of an “inordinate amount” would require state boards to report the activity to FDA and trigger certain reporting requirements.

The stated issuance of revised draft guidance would provide compounders an additional opportunity to comment on the proposed guidance.

FDA Publishes Final Guidance on Biological Products

On January 19, 2018, FDA finalized its guidance on “Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application.” The final guidance describes a way for outsourcing facilities to assign beyond use dates (BUDs) to repackaged biological products that exceed the “default” BUDs of 24 hours, based on data.

In future months, FDA will further clarify policies applicable to 503B facilities by issuing the following:

• Guidance on the “definition of a facility” in section 503B – This will address the issue of whether an outsourcing facility can be co-located with a 503A pharmacy, and whether an outsourcing facility can also manufacture FDA-approved drugs within the same facility.
• Revised draft guidance describing examples of conditions that FDA considers to be insanitary and in violation of the FD&C Act.
• Final guidance on compounding and repackaging of radiopharmaceuticals by state-licensed nuclear pharmacies, federal facilities and certain other entities, as well as compounding and repackaging of radiopharmaceuticals by outsourcing facilities.
• Revised draft guidance describing examples of conditions that FDA considers to be insanitary and in violation of the FD&C Act.
• Final rules regarding the additions and modifications to the list of drug products that cannot be compounded because the products or their components have been withdrawn or removed from the market for reasons of safety or effectiveness.

The issuance of three final guidances and FDA’s 2018 priorities plan are further evidence that FDA intends to actively oversee the regulation of drug compounding and is looking to work more closely with state boards of pharmacy to coordinate its various enforcement initiatives. As such, drug compounders should continue to closely monitor their compliance with all applicable state and federal regulation and guidance.

Client Alert 2018-026