FDA Proposal On 'Inordinate' Interstate Compounding Sparks State Oversight Debate

The US FDA’s revised draft MOU on interstate compounding, which stipulates new controls to ensure that pharmacies do not ship an “inordinate” amount of drugs across state lines, needs strong state oversight and robust information collection to work, say some groups commenting on the agreement. Yet two members of Congress are challenging the MOU on the grounds that some states and state boards of pharmacy lack the regulatory authority to implement the agreement.

A revised US Food and Drug Administration proposal to let more compounded drug products cross state lines has prompted new hand-wringing over how states will make sure compounding pharmacies do not engage in an "inordinate" amount of interstate activity.

US pharmaceutical industry and compounding pharmacy groups weighed in on FDA’s revised memorandum of understanding on interstate compounding. Respondents said that stronger state oversight is needed to ensure that compounding pharmacies do not exceed the interstate distribution of “inordinate” amounts of compounded drugs. Yet two members of Congress are challenging the MOU on the grounds that some states and state boards of pharmacy may lack the regulatory authority to implement the agreement.

The agency’s revised draft “Memorandum of Understanding (MOU) Addressing Certain Distributions of Compounded Drug Products Between the States and the U.S. Food and Drug Administration” was issued on 10 September, 2018. The deadline for comment was 10 December, 2018. FDA plans to issue a final MOU later this year.

The November 2013 Drug Quality and Security Act prompted new controls on and oversight of pharmaceutical compounding in response to the New England Compounding Center tragedy of 2012. Injectable drugs made at the NECC facility in Framingham, Massachusetts, killed 64 people and sickened at least 700 more in 20 states. Among the DQSA provisions that came out of this tragedy was a requirement for the FDA to implement new restrictions on the shipping of compounded drug products across state lines.

Section 503A of the Federal Food, Drug and Cosmetic Act (FDCA) was amended by DQSA; it requires FDA to develop a MOU to prevent the interstate distribution of “inordinate” amounts of compounded drug products and provides for appropriate investigation by a state agency of complaints relating to compounded drug products distributed interstate. The law did not specify the threshold amount, leaving it up to the agency to decide.

The law says if the state does not enter into the MOU, then the compounders are limited to a ceiling of distributing or dispensing 5% of their compounded medications interstate.

Threshold Changes

The definition of what constitutes an inordinate amount was changed from the 2015 proposed MOU. Under the 2015 draft MOU, an inordinate amount was defined as an amount of compounded drug product distributed interstate by a compounders in a given month that is equal or greater to 30% of all drug products dispensed or distributed by the compounder. The MOU did not specify how to meet this threshold.

The latest draft proposes a 50% limit. FDA changed the threshold to accommodate stakeholder concerns that the threshold could impede patient access to compounded drugs for which there is a medical need. Stakeholders said that some compounding pharmacies that specialize in drugs to treat certain medical conditions and distribute these drugs to patients nationwide would be particularly affected.

In exchange for the higher limit, the revision adds language specifying the information needed to determine whether the number of drugs shipped by compounders is under the threshold limit.

The revised MOU says that at least annually, states "will identify using surveys, reviews of records during inspections, or other mechanisms available to the state, compounding pharmacies that distribute inordinate amounts of compounded drug products interstate by collecting information regarding the total number of prescription orders for compounded drug products distributed or dispensed intrastate and the total number of prescription orders for compounded drug products distributed interstate.”

Pew Welcomes More Information

In its comments, the Pew Charitable Trusts expressed guarded support for changing the threshold limit in that it “trades limitations on the volume of compounded drugs shipped interstate for better information about those shipments.”

The group cautions, however, that strong state oversight is needed to ensure that compounders stay within threshold limits. The group said that “while this trade-off could facilitate oversight by encouraging states to better understand compounding activity within their borders and providing the FDA with information necessary to prioritize inspections, the prospect of unlimited volumes of compounded drugs crossing state lines makes robust oversight critical.”

Relaxed State Role

Yet the revision actually relaxes states’ oversight role in enforcing the MOU’s threshold requirement; FDA said this change was necessary to accommodate stakeholder concerns that states lack the regulatory authority to take a strong oversight role.

The 2015 draft MOU said that states can “take action regarding any pharmacy, pharmacists, or pharmacies that distributes inordinate amounts of compounded human dug products interstate.” It specified that state action could include a warning letter, enforcement action, suspending or revocation of license, or other action consistent with state law.

The latest revision deletes this "take action" provision and waters down the states’ role to coordinating complaints that compounders are exceeding these threshold limits.

The revised MOU says that if the state becomes aware of any physicians who are distributing compounded drug products interstate, it can “coordinate with the appropriate regulators of physicians compounding within the state to determine, using survey reviews of records during inspections or other means available to the state that physicians distribute inordinate amounts of compounded drug products by collecting information regarding the total number of prescription orders for compounded drug products distributed to dispense intrastate and the total number of prescription orders of compounded drug products interstate.”

AAM Want More Active State Role

The Association for Accessible Medicines complained about this diluted state role.

The group said that "the 2018 revised draft MOU merely requires the state to notify by email within 30 days of identifying a compounder that has distributed inordinate amounts and include certain information in the email about the compounding. AAM is concerned about the public health of patients, quicker response times and reporting would allow for quicker action to secure the safety of patients."

Robust Mechanism Needed To Collect Information

Pew said that in order for this MOU to be effective and to ensure that compounders are not exceeding limits, states should have a robust mechanism in place for collecting information.

The group said that “successful implementation of the proposed MOU will require robust state mechanisms for collecting information on compounding pharmacies. In order to provide the FDA with the information required under the proposed MOU, states will need robust mechanisms in place to collect annual information on the amount of drugs dispensed or distributed by pharmacies in their jurisdiction. Without these data, states will not be able to accurately identify compounders distributing inordinate amounts of compounded drugs or provide the FDA with the information necessary to inform inspectional priorities.”

Do States Have Regulatory Authority To Implement MOU?

The revised draft MOU recently came under fire from two members of Congress who question whether states have the regulatory authority to implement it.

In a 17 May letter to FDA Commissioner Norman Sharpless, Sen. Tammy Baldwin (D-WI) and Sen. Bill Cassidy (R-LA) said that “the newly reissued draft MOU is a meaningful step in the right direction.”

Yet they question whether some states and state boards of pharmacy have the “regulatory authority and resources to implement the MOU” which may result in their inability to sign it.

“Should states not sign the MOU, the FDA would enforce a 5% limit on interstate compounding. Many residents in our states depend on compounding pharmacies in other states to meet their unique medical needs. … A 5% limit on sending compounded drugs to other states could restrict access to vulnerable patient who depend on pharmacies that specialize in these medications, particularly for those who live in contiguous states.”

Another problem with the MOU, say the senators, is that it incorrectly commingles the terms “distribution” and “dispensing.”

The letter said that “dispensing and distributing are typically treated as distinct and separate activities but the proposed definition of distribution includes dispensing such that all compounded medications, with or without a prescription, would be considered subject to the oversight requirements.”

The Arizona State Board of Pharmacy and the New Hampshire Board of Pharmacy voiced similar concerns in their comments.