WASHINGTON, DC (November 29, 2004) – The Food & Drug Administration (FDA) last week strengthened its risk minimization action plan (RiskMap) for Accutane (isotretinoin) and its generic equivalents. Isotretinoin is a drug indicated for the treatment of severe recalcitrant nodular acne that is not responsive to other therapies.
The goal of the strengthened RiskMap is to reduce the risk of birth defects associated with fetal exposure to isotretinoin.
The strengthened RiskMap reflected agency and sponsor consideration of therecommendations from the February 2004 joint Advisory Committee of the DrugSafety & Risk Management and the Dermatologic & Ophthalmic Drug AdvisoryCommittees which examined the current isotretinoin risk management programknown as the System to Manage Accutane Related Teratogenicity, or Smart, program.
Smart was implemented in 2002 in response to agency recommendations at that time to further decrease fetal exposures to isotretinoin. The February 2004 joint advisory committee discussion focused on whether changes were necessary to Smart and its generic equivalents, based on FDA assessments of the program’s performance and its ongoing surveillance of pregnancy exposures to isotretinoin.
The committees agreed that changes were called for, especially because the Smart program, operated by Roche Pharmaceuticals, was only one of several similar programs that had been created with the introduction of generic isotretinoin to the market. The multiple programs created confusion and the concern that patients would not receive appropriate counseling and testing to prevent the possibility of birth defects.
Last week’s changes reflected a joint response by the agency and the sponsors ofisotretinoin drug products that the sponsors strengthen the isotretinoin RiskMap. Under the new program, sponsors will obtain registration of not only prescribers, but also pharmacies that dispense and patients who use isotretinoin.
The program also includes documentation of a negative pregnancy test before givingisotretinoin to women who are capable of becoming pregnant. The registration system will be built to incorporate physician and patient identification codes that will protect the privacy of patients.
The innovator and generic sponsors of isotretinoin have jointly contracted withCovance, Inc., to “design, build, implement, and operate a single strengthened isotretinoin riskMap incorporating these elements,” the FDA said. The agency said its goal was to eliminate fetal exposure to isotretinoin by ensuring that no woman start isotretinoin therapy if pregnant and no woman on isotretinoin therapy become pregnant.
The FDA, acknowledging that the program development is complex, emphasized the need to make it as unintrusive as possible for healthcare providers and patients.
The agency also asked the industry “to be mindful of the need for simplicity and minimal burden on the health care community and patients.” With that in mind, the new program will include, but will not be limited to, the following:
1) Registration of all prescribers, patients and dispensing pharmacieswill be registered in a single centralized “clearinghouse.”
2) Before a registered pharmacy first dispenses the medication for a particular patient, the following will occur:
·Completion of patient education by the prescriber;
·An appropriately timed and documented negative pregnancy test priorto dispensing the medication;
·Completion of the informed consent, education and risk managementcomponents by the patient;
·Electronic or other verification of the above actions.
3) For all subsequent prescriptions, the following will occur monthly:
·Ongoing patient education by the prescriber;
·Repeated negative pregnancy test within a specified window prior todispensing;
·Completion of the education and risk management components by thepatient;
·Electronic or other verification of the above actions.
The isotretinoin sponsors will play a large role in determining complianceand effectiveness of the strengthened RiskMap, the FDA said.
In addition to shipping the drug only to authorized distributors, the sponsors have agreed to perform the following tasks:
·Establish and maintain the clearinghouse;
·Monitor for sales of the drug outside of approved distribution channels, including via the Internet;
·Develop procedures to monitor and evaluate each component of the RiskMap to include clearinghouse compliance with specified responsibilities, prescriber and pharmacy registration and prescribing and dispensing by non-registered prescribers and pharmacies, respectively;
·Evaluate the effectiveness of the program in reducing and limiting pregnancy exposures.
In order to implement the new program, the innovator and generic sponsors of isotretinoin reached an agreement with Celgene Corp., which holds patents on a successful program for preventing pregnancy exposures to thalidomide.
The FDA said it will continue to monitor all adverse events reported with isotretinoin use in order to protect the public health.
