APA Files FOIA Request With FDA Seeking Resolution to Clozapine REMS Problems

APA has filed a Freedom of Information Act (FOIA) request to the Food and Drug Administration (FDA) seeking information pertaining to the revised Clozapine Risk Evaluation and Mitigation Strategy (REMS) that the FDA instituted on November 15, 2021.

The FOIA request is seeking information about lost patient data; how contracts are structured with the Clozapine Product Manufacturers Group (CPMG), which administers the clozapine REMS; whether the FDA or CPMG has authority to fix problems; whether the FDA has authority to oversee the contractor who administers the REMS website; and how the FDA is assessing whether the REMS is even still necessary.

The request was filed by APA alone but complements a number of actions it has taken in concert with six other advocacy organizations regarding widespread problems experienced by prescribers and pharmacies as a result of the REMS. The six other groups are the American Association for Community Psychiatry, American Psychiatric Nurses Association, College of Psychiatric and Neurologic Pharmacists, National Alliance on Mental Illness, National Association of State Mental Health Program Directors, and National Council for Mental Wellbeing.

The Clozapine REMS is a safety program required by the FDA to manage the risk of severe neutropenia associated with clozapine treatment and was originally instituted in September 2015. The REMS applies to all clozapine medicines on the market and requires the use of a centralized system to monitor Patients and prevent or manage clozapine-induced neutropenia. Prior to 2015, individual manufacturers operated their own clozapine patient registries.

On November 19, the FDA temporarily suspended some of the revised REMS requirements because of problems experienced by clinicians and pharmacies. In February, in response to a letter to the FDA from APA and the six organizations, the agency extended the suspension indefinitely. The suspension allows pharmacists to dispense clozapine without a REMS Dispense Authorization (RDA) and wholesalers to continue to ship clozapine to pharmacies and health care settings without confirming enrollment in the REMS.

The February letter also requested at least 60 days’ notice before the suspension is ended and the RDA requirement reinstated.

Additionally, in letters to the chairs and ranking members of the House Energy and Commerce Committee and the Senate Health, Education, Labor, and Pensions Committee dated February 14, APA and its partners requested a wholesale reconsideration of REMS.

Robert Cotes, MD, believes the FDA should reassess whether the Clozapine Risk Evaluation and Mitigation Strategy is necessary since it is another barrier to increasing the use of this effective medication.

“We recommended to the FDA that the REMS be suspended immediately and undergo thorough reviews,” the letters to Congress stated. “These reviews should be designed to inform the FDA and manufacturers of the problems the REMS present and potential strategies to remedy these issues. More importantly, these reviews should weigh the potential harm of the elements of the REMS and the REMS themselves against the potential benefits that the REMS may bring. Congress should also hold hearings to understand the problems with the REMS planning, rollout, and implementation and develop recommendations to improve future REMS programs.

The immediate aftermath of the introduction of the new REMS last November resulted in considerable chaos and confusion, causing some patients to discontinue treatment for a period. Prescribers experienced increased administrative time navigating the REMS website, seeking authorization for prescriptions, and trying to get questions answered. Pharmacies had problems with the enrollment process and delays and difficulties getting authorization for individual prescriptions prior to the suspension of that requirement.

Five months later, uncertainty about the REMS requirements remains, as well as concern about when the suspension of regulations on pharmacies and wholesalers will end and the RDA will be reinstated.

“Extending the temporary suspension of the REMS dispense authorization requirement was a positive step, but I have continued to hear about examples of clozapine treatment interruptions,” Robert Cotes, MD, told Psychiatric News. “Even just a few missed doses of clozapine can put a patient at risk for symptom exacerbation or hospitalization. After a patient misses a few doses of clozapine, the medication needs to be gradually restarted, and prescribers must delicately balance a number of factors to ensure the titration is not too fast to cause side effects and not too slow to risk a relapse.”

Cotes is an associate professor of psychiatry at Emory University School of Medicine and a physician expert with APA’s SMI Adviser. SMI Adviser is APA’s Clinical Support System for Serious Mental Illness.

Cotes said also it is “frustrating” that historical Clozapine REMS data from 2015-2021 are no longer available. “There are certain clinical situations where that information can be extremely valuable,” he said. “It would be really helpful to have that functionality back.

Many prescribers and advocacy groups believe the REMS requirements are unnecessary, that the risk of neutropenia is overstated, and that the requirements contribute to underutilization of a drug that has proven enormously effective in the treatment of schizophrenia.

“I would like the FDA to reevaluate the need for the Clozapine REMS and the system of routine hematologic monitoring that we have,” Cotes said. “It is really a barrier to wider access to clozapine.” ■

A copy of the FOIA request is posted here.


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