The 505(b)(2) process is used to obtain approval of an isomer of an already approved racemate. An example is cetirizine. The original product approved (Zyrtec) is a racemate. In May 2007, UCB, Inc. obtained approval for levocetirizine dihydrochloride 5 mg tablets, using the 505(b)(2) process. That approval was based on replicate clinical studies. On 1/28/2008 UCB obtained approval of a oral solution (2.5mg/5mL) of levocetirizine dihydrochloride also using 505(b)(2). The latter NDA was approved based on a single BE study comparing the oral solution to the 5 mg tablet in normal healthy adults.
A couple of interesting learning points.
The oral solution also received approval for pediatric population, satisfying the PREA commitment made when the tablet was approved. Yet the BE study was done in adults. UCB found a pk study in the literature that showed the systemic exposure (as measured by AUC) is twice as high in children aged 6 to 11 than adults – UCB then didn’t need to do the study!
How did I learn all of this? If you go to the FDA website drugs@fda you will only see the approval letter and label. Where did I get the medical review? According to section 505B(h)(1) of the Pediatric Research Equity Act of 2007 (PREA), as amended in fall of 2007 by FDAAA, the FDA must publish the medical, clinical pharmacology and statistical reviews of all approved submissions conducted in response to a written request by FDA. In this case, the letter approving the UCB levocetirizine 5 mg tablet had specific pediatric requests under PREA. The full listing of submissions appears here .
Lesson learned: Don’t leave any stone unturned when seeking public information to support your 505(b)(2).