75 years of excellence Combination Products NEMA’s Comments for the Office of Combination Products Public Hearing Terry Sweeney, Philips Medical Systems

75 years of excellence Question 2 Safety and Effectiveness should be considered on a component basis  Imaging Contrast Agent  Imaging Device (Magnetic Resonance, Ultrasound, etc.) Effectiveness should be delegated to the component with the Primary Function  Imaging system creates the image, Imaging system has the primary function.

75 years of excellence Question 2 - cont. Center with appropriate expertise in the primary function should lead the review of effectiveness  CDRH should be lead reviewer for effectiveness of imaging systems using contrast agents that have been approved for safety by CDER.

75 years of excellence Question 3 Use review process appropriate to the component  Contrast Agent: Drug safety: CDER New drug Revised dosing  Imaging Device: Imaging Efficacy: CDRH New indication Expanded indication

75 years of excellence Question 4 Use Application appropriate for the component  Contrast Agent: Drug Application processes NDA, aNDA  Imaging Device: Device application processes 510(k), PMA

75 years of excellence Question 5 Use Quality System appropriate for the component  Contrast Agent: cGMP  Imaging Device: QSR

75 years of excellence Question 6 Use adverse event reporting system appropriate for the cited component  Contrast Agent: Adverse Experience Reports  Imaging Device: Medical Device Reports (MDR)

75 years of excellence Question 7 Separate cross labeling requirements:  Use Least Burdensome provisions to set appropriate regulatory controls  Intended Use statements may be distinct based upon safety risk: Contra-indications may be applied to only one OR both components Cross-reference high-risk issues De-couple component-specific issues (i.e. effectiveness)

75 years of excellence Question 7 - cont.  Allow manufacturers of each component of a combination product to modify labeling in line with a high degree of patient protection Pharmacology: Agent manufacturer Imaging effectiveness: Device manufacturer  Allow Center with expertise in each component to review labeling for that component Contrast Agent: CDER Imaging Device: CDRH