On January 3, 2023, FDA released an updated Risk Evaluation and Mitigation Strategy (REMS) for mifepristone. The updated REMS follows a December 2021 FDA announcement that it would eliminate the requirement that mifepristone be dispensed only to patients in person at a medical facility (hospital, clinic, medical office). Polsinelli’s FDA Practice Group examines the background of this drug and the updates to the REMS, which includes a new pharmacy certification requirement.
What is Mifepristone?
Mifeprex (mifepristone) and its generic Mifepristone Tablets (collectively mifepristone) are approved, in a drug regimen with misoprostol, to end pregnancy through ten weeks gestation (70 days or less since the first day of a patient’s last menstrual period).
In 2000, the FDA approved Mifeprex and imposed distribution restrictions on the drug. In 2011, these initial distribution restrictions became the basis of the REMS Mifepristone Program. In 2019, with the approval of the generic Mifepristone Tablet, the REMS Mifepristone Program became a single, shared system applied to both Mifeprex and the generic mifepristone.
What is a “REMS” Program?
The FDA holds the authority to require a Risk Evaluation and Mitigation Strategy (“REMS”) for the dispensing of a drug. FDA reviews the need for a REMS based on a drug’s safety profile and whether the medication’s benefits outweigh its risks. The FDA also has the authority to revise or remove a drug’s REMS based on an evaluation of safety data.
FDA’s decision to impose REMS on mifepristone has been controversial, leading to multiple lawsuits challenging the REMS. During the pandemic, FDA used enforcement discretion to “waive” the in-person requirement.1 The recent decision to require pharmacy certification is also controversial, as many physician groups and pro-choice advocates view the pharmacy certification requirement as unnecessary, while other groups view the availability of mifepristone by mail as circumventing state restrictions on abortion. Further litigation against FDA is likely.
Prior Requirements of the Mifepristone REMS Program?
From 2011 until December 16, 2021, the Mifepristone REMS Program had three elements:
(1) In-person dispensing requirement. Mifepristone could only be administered in a clinic, hospital, or under the direct supervision of a certified medical provider to the patient. This barred drug availability in retail pharmacies and/or delivery by a mail-order pharmacy.
(2) Clinician certification. A clinician was required to be certified to dispense the drug by submitting a Prescriber Agreement Form to the drug distributor before prescribing mifepristone.
(3) Patient Warning. Patients were required to sign an FDA-approved Patient Agreement Form before a clinician could dispense the drug.
On December 16, 2021, the FDA modified the REMS for mifepristone by:
(1) Removing the in-person dispensing requirement, which was not being enforced.
(2) Maintaining the prescriber certification and patient agreement processes.
(3) Adding the “certified pharmacy” dispensation option. This option signaled a willingness to allow patients to receive the drug by mail through certified prescribers or pharmacies.
What are the New Modifications to the Mifepristone REMS Program?
On January 3, 2023, FDA released its new Mifepristone REMS Program requirements. Any pharmacies, including a mail order pharmacy, that become certified under the Mifepristone REMS Program may dispense the drug directly to patients that have a prescription from a certified mifepristone prescriber, as long as all REMS Program requirements are met, including the requirement that a prescriber agreement is provided or on file with the certified pharmacy. These modifications are highlighted on FDA’s Mifepristone Information Page and in updates to the associated Questions and Answers page.
Effective January 3, 2023, any pharmacy wishing to dispense mifepristone must execute the required pharmacy agreement with either Danco Laboratories or GenBioPro, Inc. (available here). These agreements summarize FDA’s Mifepristone REMS Program requirements, which, in brief, require that the pharmacy:
(1) Be able to receive the FDA-approved Prescriber Agreement Forms by email and fax.
(2) Be able to ship mifepristone using a shipping service that provides tracking information and track and verify receipt of each shipment of Mifeprex or mifepristone.
(3) Designate an authorized representative to carry out the certification process on behalf of the pharmacy.
(4) Ensure the authorized representative oversees implementation and compliance with the Mifepristone REMS Program, which includes, among other requirements, the completion of a Pharmacy Agreement Form for each pharmacy location (a blanket Pharmacy Agreement for a chain of pharmacies is not compliant).
(5) Ensure that mifepristone is only dispensed pursuant to prescriptions that are written by certified prescribers.
(6) Verify that the prescription is issued by a certified prescriber by confirming their completed Prescriber Agreement form was received with the prescription or is on file with the pharmacy.
(7) Ensure mifepristone is dispensed to the patient in a timely manner – defined as delivered to the patient within four calendar days of receipt of the prescription (unless an exception applies).
Additional packaging, reporting, record keeping, confidentiality, training, and audit requirements apply. All requirements are listed in each Pharmacy Agreement Form.
As of November 23, 2022, there are twenty-four states and the District of Columbia where abortion is available, and no telehealth medication abortion restrictions exist.2 Polsinelli’s FDA Practice Group encourages pharmacies to review both federal and state guidelines as dispensing of mifepristone by mail remains subject to state-specific regulations. Many states have created a variety of policies addressing access to abortion services. Examples include establishing policies that require patients seeking abortion services to come in person to access such services, state specific policies regarding restrictions or bans applied to the dispensing of mifepristone, and direct bans against the use of telehealth in accessing abortion services. These restrictions arguably create a question of preemption. Some stakeholders argue that the Mifepristone REMS Program should preempt state law as the scope of FDA’s review in the modification of the Mifepristone REMS Program contemplated factors that some states are attempting to address in direct contradiction to FDA’s stated view. Others posit that the Mifepristone REMS Program would not preempt more stringent state laws. Ultimately, litigation around these questions is more than likely.
This modified FDA Mifepristone REMS Program may ease some dispensing restrictions, but questions remain regarding out-of-state providers providing telehealth abortion services across state lines or the limits of state action in prosecuting or protecting clinicians in the states where they reside. Additionally, distribution issues remain at the forefront as mail-order pharmacies delivery of medications across state laws still presents choice of law issues.
1 In April 2021, during the COVID-19 public health emergency, FDA announced it would exercise enforcement discretion on the in-person dispensing requirement. In a letter to the American College of Obstetricians and Gynecologists and the Society of Maternal-Fetal Medicine, acting commissioner Janet Woodstock stated that “the FDA would exercise discretion to permit the dispensing of mifepristone through the mail when done by or under the supervision of a certified prescriber; or through a mail order pharmacy under the supervision of a certified prescriber.”
2 See Kaiser Family Foundation: Women’s Health Policy, The Availability and Use of Medication Abortion: Table 3 Abortion-Related Policies That Affect Access to Medication Abortion as of November 23, 2022, KFF.org (January 4, 2023), available here.
