The United States Food and Drug Administration (FDA) required the companies marketing the drug in the US, which at the time that iPLEDGE was launched were Roche, Mylan, Barr, and Ranbaxy, to put this website in place as a risk evaluation and mitigation strategy. These companies formed a group called the Isotretinoin Products Manufacturing Group, and it hired Covance to run the website. Prescribers, pharmacists, and all people to whom the drug is prescribed need to register on the site and log information into it. Women with child-bearing potential must commit to using two forms of effective contraception simultaneously for the duration of isotretinoin therapy and for a month immediately preceding and a month immediately following therapy. Additionally, they must have two negative pregnancy tests 30 days apart and have negative pregnancy tests before each prescription is written. Adverse effects
Increasingly higher dosages will result in higher toxicity, resembling vitamin A toxicity. Adverse effects include:

Possible permanent effects
Isotretinoin may stop long bone growth in young people who are still growing. Premature epiphyseal closure can occur in people with acne receiving recommended doses of Accutane.Generally, though, premature epiphyseal closure seems to be primarily related to:

high doses of isotretinoin beyond the recommended dose of 1 mg/kg/day
long-duration beyond the usual course of what is required for an acne patient for treatment (usually 5–7 months)
early onset of treatment (young teenage age 12–14 or younger)Isotretinoin is known to cause meibomian gland dysfunction which causes persistent keratoconjunctivitis sicca (dry eye).
Roche implemented those measures, and offered to pay for contraception counseling and pregnancy testing for women prescribed the drug; the program was called the "Pregnancy Prevention Program". A CDC report published in 2000 showed problems with the Pregnancy Prevention Program and showed that the increase in prescriptions was from off-label use, and prompted Roche to revamp its program, renaming it the "Targeted Pregnancy Prevention Program" and adding label changes like requirements for two pregnancy tests, two kinds of contraception, and for doctors to provide pharmacists with prescriptions directly; providing additional educational materials, and providing free pregnancy tests. The FDA had another advisory meeting in late 2000 that again debated how to prevent pregnant women from being exposed to the drug; dermatologists testified about the remarkable efficacy of the drug, the psychological impact of acne, and demanded autonomy to prescribe the drug; others argued that the drug be withdrawn or much stricter measures be taken.