FDA Stands Firm on Deadline for Clozapine REMS Recertification

Kerry Dooley Young

November 12, 2021

Despite objections from the American Psychiatric Association (APA) and other national groups, federal regulators are sticking to the November 15 deadline for the modified clozapine risk evaluation and mitigation strategy (REMS) program.

The modifications will require all those who prescribe and dispense clozapine to be recertified. Prescribers and pharmacies who fail to be certified by this date will no longer be able to prescribe/dispense the drug. In addition, clinicians must re-enroll all patients who are currently taking the medication.

Clozapine is used to treat schizophrenia that is not well controlled with standard antipsychotics. It is also prescribed to patients with recurrent suicidal behavior associated with schizophrenia or schizoaffective disorder.

Although it is highly effective in some patients, it also carries serious risks. Specifically, it can decrease the neutrophil count, which can lead to severe neutropenia, serious infections, and death. As a result, those taking the drug must undergo regular absolute neutrophil count (ANC) monitoring. Clozapine REMS is intended to maximize the benefits of the drug and minimize risk.

The US Food and Drug Administration (FDA) first announced modifications to the program in July. Under the new rules, pharmacies will no longer be permitted to use telecommunication verification, also known as the switch system, to verify safe use conditions. Instead, the authorization to dispense will be obtained either through the contact center or online via the REMS website.

Furthermore, a new patient status form (PSF) will be used to document absolute ANC monitoring for all outpatients and the form must be submitted monthly.

In addition to the APA, opponents of the new recertification rules include the College of Psychiatric and Neurologic Pharmacists (CPNP), the National Council for Mental Wellbeing, the National Association of State Mental Health Program Directors, the National Alliance on Mental Illness, the American Psychiatric Nurses Association, and the American Pharmacists Association.

No More Access to Patient Data

Among other concerns, the coalition argues the new requirements will make it more difficult for clinicians to access data on patients' previous clozapine history. Many clinicians depend on these data, which were maintained in the earlier REMS and in previous manufacturer-maintained clozapine monitoring systems.

The FDA told Medscape Medical News in a statement that the Clozapine Products Manufacturers' Group (CPMG) "was not able to incorporate this data into the modified REMS database due to technical reasons. The new REMS contact center will have access to the historical data should a healthcare provider need the information," the FDA said.

The FDA could not immediately provide Medscape Medical News with more detail on the nature of the "technical reasons" cited as a cause for the new hurdle that prevents clinicians from accessing these previously available data.

In a September letter to the FDA, the coalition pushed back, writing that it is "unreasonable to deny prescribers of this data that they entered. Furthermore, the lack of historical data could result in harm to patients in some circumstances."

The coalition asked the FDA to intervene and ask the drug's manufacturers to reinstate prescriber access to the information.

In a response to questions on this issue from Medscape Medical News, the FDA said in a written response the historical data had not been lost, but would be maintained "for record-keeping purposes."

The FDA also said agency officials met on October 10 with members of the professional organizations who authored the letter to hear their concerns about the clozapine REMS program. The CPMG, which has the responsibility for implementing the REMS, was also represented at the meeting, the FDA said.  

"Based on concerns raised by stakeholders, the CPMG has recently begun to address some of the concerns raised in the letter including updating the prescriber/prescriber designee relationship and enrollment process to allow for a designee to be affiliated with multiple prescribers," the FDA told Medscape Medical News.

"The recent updates also enable prescriber designees to self-enroll/create credentials, send affiliation requests to prescribers, and attest/perform functions on behalf of prescribers. It is our understanding that the CPMG is disseminating this information to stakeholders," the agency added.

Bigger Burden, Bad Timing

In an interview with Medscape Medical News, Robert Cotes, MD, who serves as a member of the clinical expert team for SMI Adviser, a joint initiative of the APA and the Substance Abuse and Mental Health Services Administration (SAMHSA), said the changes to the clozapine REMS will likely increase the administrative burden on clinicians, Cotes said.

In the letter to the FDA, the APA and other groups in the coalition expressed concern about patient status forms, which are five pages long. The coalition has requested that the FDA develop a form where clinicians can submit monitoring results on multiple patients at one time, with PDF forms presented in a fillable format.

"The concern is that if the workflows become more laborious for people, it could result in treatment interruptions for individuals on clozapine or potentially it may steer prescribers away from using clozapine for people who may need it," said Cotes.

Also commenting for Medscape Medical News, Raymond C. Love, PharmD, professor and vice chair at the University of Maryland School of Pharmacy, emphasized the poor timing of the switch to a new clozapine REMS.

"Pharmacies are overloaded right now due to COVID tests and influenza and COVID boosters and COVID vaccinations for kids," making it a tough time to manage the demands of the clozapine REMS re-enrollment, he said.

Kerry Dooley Young is a freelance journalist based in Washington, DC. She is the core topic leader on patient safety issues for the Association of Health Care Journalists. Young earlier covered health policy and the federal budget for Congressional Quarterly/CQ Roll Call and the pharmaceutical industry and the FDA for Bloomberg. Follow her on Twitter: @kdooleyyoung

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