TABLE 2.
Clinical Evidence Supporting NDA Approval of Prescription Drugs After Facing UDI Regulatory Action or Receiving Voluntary Approval (N = 19)a
| Drug | Efficacy Evidence | Safety Evidence |
|---|---|---|
| Atropine sulfate ophthalmic solution | Literature review of 57 studies from 1931-2013; 8 studies summarized in application (3 randomized, 2 double-blind, average 173 subjects) | Literature review and statement of long history and frequent use |
| Carbinoxamine | 2 bioequivalence studies; reviewed 4 studies from 1954-1956 (2 placebo-controlled, average 105 subjects) involved in DESI review of initial carbinoxamine product | Safety events from 2 bioequivalence studies; reviewed side effects in 4 studies from 1954-1956 from DESI review |
| Codeine phosphate combinations | 2 bioequivalence studies | 2 bioequivalence studies; summary of data from 2 clinical pharmacology studies, postmarketing spontaneous adverse events report, and a literature survey |
| Codeine sulfate tablet | 5 bioequivalence studies, literature review of 159 studies; 6 studies from 1970-1978 used to support approval (all randomized, double-blind, placebo-controlled, average 127 subjects) |
Based on safety reported in labeling of reference product (codeine in Tylenol #3) |
| Colchicine tablet | Conducted clinical trial (randomized, double-blind, placebo-controlled, 1-week-long, 185 subjects); referenced 1 clinical trial from 1987 in published literature (randomized, doubleblind, placebo-controlled, 43 subjects) | Conducted clinical trial; data from 14 pharmacokinetic studies (total 314 subjects); literature review (3 randomized controlled studies and 21 uncontrolled studies); review of FDA and World Health Organization postmarketing adverse event report databases |
| Epinephrine injection/syringe | Recommended dosing based on published literature and established clinical practice; based on previous findings for epinephrine in treatment of allergic reactions and anaphylaxis | Based on previous findings for epinephrine in treatment of allergic reactions and anaphylaxis |
| Hydrocodone | 1 bioequivalence study; literature review | 1 bioequivalence study; literature review (5 studies); review of adverse events reporting system database |
| Hydromorphone injection | None based on prior approval of hydromorphone products | None; based on prior approval of hydromorphone products |
| Levothyroxine injection | Literature review of 45 studies from 1953-2007 (1 open-label trial involving 14 subjects) | Literature review of 40 studies from 1964-2004 (1 open-label trial involving 14 subjects) |
| Morphine sulfate immediate-release tablet | 3 bioequivalence studies | 3 bioequivalence studies |
| Morphine sulfate injection | Previous findings for reference product but no bioequivalence studies; literature review of 59 studies involving randomized controlled trials | Previous findings for reference product but no bioequivalence studies; literature review of 59 studies involving randomized controlled trials |
| Morphine sulfate solution | 1 bioequivalence study | Previous findings from reference product |
| Oxycodone immediate-release tablet | 2 bioequivalence studies; literature review of 10 studies | 2 bioequivalence studies; literature review of 10 studies |
| Oxycodone solution | 1 bioequivalence study | 1 bioequivalence study |
| Pancrelipase | 1 clinical trial (randomized, double-blind, placebo-controlled, length of 2 weeks, 32 subjects); literature review of 15 randomized, double-blind, placebo-controlled studies (average 40 subjects, 23 days in length) | 1 clinical trial (randomized, double-blind, placebo-controlled, length of 2 weeks, 32 subjects) |
| Phenylephrine hydrochloride (IV solution) | Literature review only; no review of protocols, study reports, datasets, case reports, or site visit; however, approved based on generally consistent conclusions overall | Literature review; review of pharmacovigilance database; review of spontaneous reporting system and adverse event reporting system databases |
| Phenylephrine hydrochloride (ophthalmic solution) | Literature review of 5 studies from 1967-2004 (average 24 subjects) | Literature review of 25 studies from 1939-2010 (8 clinical trials, average 52 subjects) |
| Potassium chloride oral solution | Previous findings for reference product, but no bioequivalence studies; literature review | Previous findings for reference product but no bioequivalence studies; literature review |
| Vasopressin | Literature review of 19 studies from 1997-2012 (11 randomized, 8 double-blind, average 62 patients) | Literature review of 19 studies from 1997-2012 (average 42 subjects) |
aClinical evidence was reviewed for the first NDA-approved drug product after 2006 through either voluntary compliance or after issuance of UDI warning letters.
DESI = Drug Efficacy Study Implementation; FDA = U.S. Food and Drug Administration; IV = intravenous; NDA = New Drug Application; UDI = Unapproved Drugs Initiative.