How long has it taken for a Final Standard Memorandum of Understanding (MOU) for States regarding Compounding Pharmacies to be issued? Are States or appropriate agencies (referred to as States below) ready to sign, acquire infrastructure, hire the necessary human resources, develop the enabling documentation, execute the requirements of the provisions, create the necessary records, and communicate data and information with the FDA in the times required of this MOU? And how long will this take, and will the FDA continue to use enforcement discretion?
This week, the FDA announced the availability of a final standard, “Memorandum of Understanding Addressing Certain Distributions of Compounded Human Drug Products Between the [insert State Board of Pharmacy or Other Appropriate State Agency] and the U.S. Food and Drug Administration,” that describes the responsibilities of a State Board of Pharmacy or other appropriate State agency that chooses to sign the MOU in investigating and responding to complaints related to human drug products compounded in such State and distributed outside such State, and in addressing the interstate distribution of inordinate amounts of compounded human drug products.
The final MOU was developed in consultation with the National Association of Boards of Pharmacy (NABP) and requires investigation and response to complaints for human drug products compounded and distributed outside of the state signing the MOU, and address the interstate distribution of inordinate amounts of compounded human drug products.
Work on a draft MOU began well in advance of January 1999 when the FDA, working with the NABP, announced the availability of the draft MOU (64 FR 3301) for public comment. Based on over 6,000 comments and litigation over the constitutionality of the advertising, promotion, and solicitation provisions in Section 503A of the FD&C Act, the MOU was never finalized.
In 2013, Section 503A was amended by the Drug Quality and Security Act (DQSA, enacted November 2013). The DQSA addresses the conditions that must be satisfied for human drug products compounded by a licensed pharmacist or physician to be exempt from GMPs, labeling of drugs with adequate direction for use, and approval of drugs under a New Drug Application or an Abbreviated New Drug Application. One condition to qualify for these exemptions is that the state where the drug product is compounded has signed a MOU with the FDA that addresses inordinate amounts of interstate distribution or, for states that do not sign a MOU, that compounding pharmacies will not distribute in excess of 5% of their total prescription orders interstate. Another condition that must be met is that all compounded human drug products must be identified for an individual patient and based on a valid prescription.
After the 2013 DQSA, the FDA made a draft MOU available in 2015 and received over 3,000 comments. Based on these comments and consultation with the NABP, the FDA reissued a draft MOU in September 2018 and received just 38 comments on this draft.
In consultation with the NABP, the FDA considered all comments from the 2015 and 2018 drafts and developed the final MOU.
Drug products compounded for veterinary use, repackaged drug products, biological products subject to licensure through a biologics license application under section 351 of the Public Health Service Act (42 U.S.C. 262), and drug products compounded by outsourcing facilities under section 503B (FD&C Act) are not the subject of this MOU.
Key provisions that the states must follow are:
- They must follow their policies and procedures (enabling documentation) and conduct investigations for any received adverse drug experiences and product quality issues for human drug products compounded within the state and distributed outside the state.
- If the complaint is substantiated, they must take action.
- Maintain records of complaints received, investigations, responses to complainants, and other data and information.
- Notify the FDA by submission to an Information Sharing Network or by email to the FDA at StateMOU@fda.hhs.gov no later than five business days after receiving a serious adverse event report or a serious product quality complaint, and provide the name and contact information of the complainant, name and address of the pharmacy involved, and a description of the complaint and compounded drug product.
- Share the results of their investigation and actions with the FDA.
- Notify the appropriate state agency regulating physicians if the complaint is for a human drug product compounded by a physician.
States will need to have personnel, infrastructure, standard operating procedures, protocols, and processes for conducting the requirements of the provisions.
For purposes of the final MOU, for states signing the MOU, a pharmacy will have distributed an inordinate amount of compounded human drug products if the number of interstate-distributed prescriptions exceeds 50% (30% in the 2018 draft MOU) of their total compounded prescriptions sent out in the same calendar year.
States that sign the MOU agree to, on an annual basis, identify (from inspections, surveys, or other means) pharmacies that distribute greater than 50% of total compounded human drug products interstate with the information broken down by the number of sterile and nonsterile compounded products, names of the states in which the pharmacy is licensed, names of states where distributed, and whether the State inspected the pharmacy and found that the pharmacy distributed compounded human drug products without valid prescriptions. The States are also required to notify the FDA within thirty days of identifying any pharmacy distributing inordinate amounts of compounded products via the Information Sharing Network or by email. The notification is to include: the name and address of the pharmacy; the number of prescriptions sent out of state; the number compounded per year and picked up at the pharmacy; the number distributed interstate; the number of sterile compounded products, and the number of states where distributed.
The final MOU lays out changes from previous draft MOUs, contains definitions and discussions of the provisions, and includes statements that all requirements of the DQSA must be followed.
For states that do not sign the MOU, pharmacies are restricted to distributing no more than 5% of their total compounded products interstate.
The FDA continues to recognize that these compounders are primarily overseen by the States but will still act or use its enforcement discretion for violations of Section 503A.
Happy Halloween and watch for flying witches.