Rosa's Approach

FDA Perspective on M&S

2004

"... computer-based predictive models [are] urgently needed to improve predictability and efficiency [of drug development] "

2005

"[models] provide a more rational basis for dose selection…, reduce the number of cycles involved in a NDA review, and improve the efficiency of drug development."

2005

"FDA ... supports ... [M&S] as a fundamental way to improve communication between the FDA and sponsors, beginning as early as the pre-IND phase."

2009

The Division of Pharmacometrics at the FDA was established "to enhance the use of quantitative methods in drug development and in the review of INDs and NDAs".

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Supporting Regulatory Submissions

Rosa’s services support our client’s discussions with and submissions to regulatory agencies.  Rosa clients often request modeling documentation developed specifically for regulatory discussions.

Since 2004, the FDA’s “Critical Path Initiative” has encouraged the use of modeling and simulation (M&S) to enhance sponsor development programs, facilitate communications between sponsors and the agency, and improve the agency’s ability to review IND, NDA, and other submissions throughout development. See our cases for examples.

M&S involvement in FDA reviews increased in 2007, and is expected to double or triple by 2011.

The FDA has made many regulatory decisions based on drug-disease modeling, for example:
  • Gabapentin for post-herpetic neuralgia: Multiple doses approved without further studies
  • Pediatric indication for trileptal: Monotherapy indication and dosing without an efficacy trial
  • Zoledronic acid subgroup inclusion: Approved dosing for renally impaired with clinical study
  • Risk management of busulfan in pediatrics: recommended label TDM without clinical study
  • Approvable calcium channel blocker: Approval of more optimal dosing with new trials

 

References:
Gobburu J and Marroum P 2001 Clin Pharmacokin 40:883-892
FDA 2004: Stagnation or Innovation: Challenge & Opportunity on the Critical Path to New Medical...
Korn D, Stanski D 2005: Drug Development Science-Obstacles and Opportunities...
Bhattaram VA et al. 2005 AAPS J 7:E503-E512
Bhattaram VA et al. 2007 Clin Pharmacol Ther 81:213-221
Lalonde RL et al. 2007 Clin Pharmacol Ther 82:1
Lesko L 2007 Clinical Trial Simulations in the Critical Path Initiative and Regulatory Decision-Making
Gobburu J and Powell B 2007 (Powerpoint slides) Pharmacometrics Impact on FDA Decision-Making...