• Reminder systems, processes, or forms to foster reduced-risk prescribing and use.

  • Performance-linked access systems that guide prescribing, dispensing, and use to target the population and conditions of use most likely to confer benefits and to minimize particular risks.

NDAs for NMEs are required to include RiskMAPs, but at the time of approval most non-NMEs will not need RiskMAPs. Known risks can be addressed through standard industry and CDER activities. Information about possible risks can be sufficiently uncertain that appropriate minimization strategies are not obvious.

RiskMAPs can also be developed or modified after marketing. Every RiskMAP should be viewed as a “living document” that evolves throughout the lifecycle of a drug. One of the best examples is the case of isotretinoin, a teratogenic drug indicated for severe cystic acne. The risk minimization activities for this drug have increased in complexity. The Pregnancy Prevention Program (PPP) was established in 1988 in an attempt to prevent exposure of pregnant women to isotretinoin. The PPP asked female users of isotretinoin to enroll voluntarily in a survey administered by Boston University’s Sloane Epidemiology Unit and enrolled 45 percent of women of reproductive age who were using the drug. Of these women, 36 percent did not have any type of pregnancy test before beginning treatment, and about 900 pregnancies occurred among enrollees during 1989–1998 (No Author, 2000). A new program, SMART (System to Manage Accutane Related Teratogenicity), was implemented in 2002 (Levine A, 2002; Honein et al., 2004). SMART retained the voluntary registration of PPP and

  • Added a requirement for two negative pregnancy tests before the first prescription with the second pregnancy test occurring during menses.

  • Added qualification stickers on each prescription to confirm that the patient had agreed to use contraception and had signed an informed consent about the teratogenic risks posed by isotretinoin and to verify that the physician had confirmed the negative pregnancy tests and had counseled the patient about participation in the voluntary followup survey.

  • Added a requirement that prescriptions not be filled without a qualification sticker.

  • Added a requirement that prescriptions not be filled more than 7 days later than the qualification date on the sticker.

  • Added a restriction that limited all prescriptions to a 30-day supply.

  • Disallowed automatic refills and telephoned-in prescriptions.



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