REMS

Maria G. Tanzi, PharmD

After recent FDA-approved changes to the clozapine REMS program and the isotretinoin REMS program known as iPLEDGE, users of both programs are experiencing issues.

“We understand that this has caused frustration and has led to patient access issues for clozapine,” FDA said in a December 2, 2021, statement. “FDA takes these concerns seriously. Continuity of care, patient access to clozapine, and patient safety are our highest priorities.”

In a January 14, 2022, statement about the isotretinoin REMS issue, FDA expressed similar sentiments saying they “share the frustration and disappointment of many iPLEDGE users about the duration of this interruption and the impact these issues are having on access to treatment for many patients.”

Clozapine REMS requirements on temporary hold

On July 29, 2021, FDA approved modifications to the clozapine REMS program, which went into effect on November 15, 2021. These changes included the recertification of all prescribers and pharmacies, re-enrollment of all patients receiving clozapine, and a new patient status form with absolute neutrophil count submitted monthly. Additionally, pharmacies are no longer able to use the telecommunication verification (i.e., “switch system”) to verify safe use conditions. The authorization to dispense must now be obtained through the contact center or via the REMS website.

Since the changes went into effect, clinicians have reported issues with the clozapine REMS contact center such as high call volumes and long wait times. These issues are impacting access to clozapine, and abrupt discontinuation of the drug can result in significant complications for patients.

Because of these concerns with the clozapine REMS program, FDA is temporarily exercising enforcement discretion with respect to certain program requirements. Specifically, pharmacists can temporarily dispense clozapine without a REMS dispensation authorization and wholesalers can temporarily ship clozapine to pharmacies and health care settings without confirming their enrollment in the REMS program. However, FDA does encourage pharmacists and prescribers to continue to work with the clozapine REMS program to complete certification and patient enrollment.

Issues with iPLEDGE

On December 13, 2021, modifications to the iPLEDGE REMS program went into effect. This included a change in the REMS administrator and a removal of the “switch” pharmacy management system as a method to verify authorization to dispense isotretinoin.

Pharmacists can no longer use the switch system to obtain a predispense authorization known as a risk management authorization (RMA) and must now obtain an RMA prior to dispensing isotretinoin by accessing the iPLEDGE REMS website or by calling the iPLEDGE REMS contact center.

Additionally, patient risk categories in the iPLEDGE REMS were reduced from three options to two, with the two new risk category options being either 1) patients who can get pregnant or 2) patients who cannot get pregnant.

Health care providers must assign and confirm their currently enrolled patients’ risk category for each patient upon their first login into the iPLEDGE REMS website on or after December 13, 2021.

Unfortunately, since the December 13 implementation date, FDA became aware of issues with the iPLEDGE program such as problems merging data from the old system to the new system, the inability of many participants to log into the website or gain access to their accounts, and long call center wait times.

Prescribers, pharmacists, and patients have all reported problems with the new iPLEDGE system. In a press release from December 16, 2021, the Society of Dermatology Physician Assistants urged FDA to take immediate action to remedy the situation, which is negatively impacting patient care by causing disruptions in access to isotretinoin.

FDA noted on January 14, 2022, that they continue to communicate with the Isotretinoin Products Manufacturers Group (IPMG) about their progress to resolve user-access issues. The agency said that IPMG recently created a new tool within the system to help resolve account access issues via an emailed login link without having to use the call center.

“While we consider potential steps within the scope of FDA’s authorities, we will continue to meet with the IPMG for updates on the status of the problems with the iPLEDGE REMS and their progress toward having the system work as intended for all users,” FDA stated. ■

Tanzi is an employee of Incyte Corporation. The opinions expressed in this article are those of the author and do not represent the views of Incyte.