FDA’s orphan drug regulations provide three independent bases under which orphan drug designation can be revoked – if FDA finds that:(1) The request for designation contained an untrue statement of material fact; or(2) The request for designation omitted material information required by [21 C.F.R. Part 316]; or(3) FDA subsequently finds that the drug in fact had not been eligible for orphan drug designation at the time of submission of the request therefor. [(21 C.F.R. § 316.29(a))]FDA rarely rescinds orphan drug designation. We are aware of only three instances:(1) Papaverine – On February 6, 1992, OOPD designated Pharmedic Co.’s papaverine topical gel for the “treatment of sexual dysfunction in spinal cord injured patients.”

– Received orphan drug designation 10/14/2015 for “treatment of hypertension in pediatric patients 0 through 16 years of age”Enalapril Maleate Powder for Oral Solution (Silvergate Pharmaceuticals, Inc.) – Received orphan drug designation 1/30/2013 for “treatment of hypertension in pediatric patients)Per the Orphan Drug Regulations (21 C.F.R. § 316.29(a)), the Agency can revoke an orphan drug designation for three reasons:The request for designation contained an untrue statement of material fact;The request for designation omitted material information required by the Orphan Drug Regulations]; orFDA subsequently finds that the drug in fact had not been eligible for orphan drug designation at the time request was submitted .FDA revocation of an orphan drug designation is not unheard of, but it doesn’t happen that often. So it is significant that the Agency recently reviewed and decided to revoke four individual designations.

Interestingly, FDA notes in its designation recommendation that the sponsor should present certain information to the Agency post-approval to support the cost recovery designation. FDA states that “[t]his information should be presented . . . after a certain period of postmarketing experience is available . . . . At each of these time points, [FDA] will need to determine if the designation and/or marketing exclusivity should remain in place or whether the designation and/or exclusivity should be revoked as permitted under 21 CFR 316.29.”