1. Critical Path Initiative: Challenges and Opportunities Ajaz S. Hussain, Ph.D. Deputy Director, Office of Pharmaceutical Science, CDER, FDA 19 October 2004 ACPS Meeting

2. CDER Goals: 2005 State of CDER 2004; Steven Galson & Doug Throckmorton October 6, 2004

4. March 2004: www.fda.gov/oc/initiatives/criticalpath/whitepaper.pdf Translational Research Critical Path Initiative

6. R&D Spending

7. But, New Product Submissions Have Remained Flat * for NMEs submitted prior to 1992, type A and type B applications are counted as Priority review and type C applications are counted as Standard review.

14. Applied Science Needed to Better Evaluate and Predict on 3 Key Dimensions on 'Critical Path' of Development

32. X(2.1) = Design Variables for the P2 section (2.1) Y(1.1)(2.1) = Linking variable that are evaluated in section (1.1) and required in section (2.1) as the input f(2.1) = Objective function addressed by section (2.1) g(2.1) = Constraints in section (2.1)  f = Mean of objective function f  f = Standard deviation of objective function f  X= Deviation range of design solution (a design space boundary) 2.1.1 Drug Substance 2.2.1 Formulation Development X(1.1) f(1.1) g(1.1) Y(1.1)(2.1) X(2.1) f(2.1) g(2.1) Y(1.1.)(*.*) Y(*.*.)(1.1.) Y(2.1)(1.1) Y(*.*)(2.1) Y(2.1.)(*.*) API Manufacturing Process or Quality control unit