Food And Drug Administration Science Advisory Board Meeting - Nov Pharmaceutical Industry - where to? More real time process control More real time process control More real time non destructive product testing More real time non destructive product testing Parametric release Parametric release Expected Results Higher product quality and security Higher product quality and security Substantial cost reduction Substantial cost reduction Benefits to share holders Benefits to share holders Benefits to the public Benefits to the public

CAN WE LEARN FROM OTHER INDUSTRIES? Pharmaceutical Industry Aircraft Engines Industry Both “hold” people’s lives in their hands Both “hold” people’s lives in their hands Both are Federally regulated Both are Federally regulated Both are very competitive Both are very competitive Both drive their products to extreme performance limits Both drive their products to extreme performance limits Both are being “chased” by generic products Both are being “chased” by generic products Both are driven to lower prices by government and users Both are driven to lower prices by government and users Food And Drug Administration Science Advisory Board Meeting - Nov

Food And Drug Administration Science Advisory Board Meeting - Nov CAN WE LEARN FROM OTHER INDUSTRIES? Aircraft Engine Industry in the mid-1970’s Product testing - Major Quality thrust during production Product testing - Major Quality thrust during production P&W incoming/in-house testing lab people at East Hartford only P&W incoming/in-house testing lab people at East Hartford only Ratio inspectors/operators - about 2 to 3 Ratio inspectors/operators - about 2 to 3 Operators not responsible for quality - inspectors are Operators not responsible for quality - inspectors are Statistical Process Control - non existent Statistical Process Control - non existent Scrap factory - about 20 to 30% Scrap factory - about 20 to 30%

Food And Drug Administration Science Advisory Board Meeting - Nov CAN WE LEARN FROM OTHER INDUSTRIES? Aircraft Engine Industry since the early-1980’s Active and statistical process control - Major Quality thrust (TQM) Active and statistical process control - Major Quality thrust (TQM) P&W incoming/in-house testing people world wide P&W incoming/in-house testing people world wide Ratio inspectors/operators - about 1 to 8 Ratio inspectors/operators - about 1 to 8 Operators responsible for quality Operators responsible for quality Scrap factory - down to 5 to 8% Scrap factory - down to 5 to 8% Quality - dramatic increase, engine failures became rare Quality - dramatic increase, engine failures became rare Cost - dramatic reduction (typical cast blade down by factor of 3-4) Cost - dramatic reduction (typical cast blade down by factor of 3-4)

Food And Drug Administration Science Advisory Board Meeting - Nov CAN WE LEARN FROM OTHER INDUSTRIES? Pharmaceutical Industry Today Product testing - Major Quality thrust Product testing - Major Quality thrust On line active process control - minimal On line active process control - minimal Ratio QC /operators - about 1 to 2???? Ratio QC /operators - about 1 to 2???? Statistical Process Control - practically non existent Statistical Process Control - practically non existent Scrap factory - ???? Scrap factory - ???? Still too many recalls - about 200 per year. Still too many recalls - about 200 per year. Product uniformity - still an unresolved issue Product uniformity - still an unresolved issue

Food And Drug Administration Science Advisory Board Meeting - Nov CAN WE LEARN FROM OTHER INDUSTRIES? Engine Industry - Drivers for Change Government and customer pressure to reduce cost to own/operate Government and customer pressure to reduce cost to own/operate Competition for performance Competition for performance Pressure to maintain profitability/share owners Pressure to maintain profitability/share owners Sense of “dead end” in doing more of the same Sense of “dead end” in doing more of the same FAA provided strong support anticipating the benefits to the public FAA provided strong support anticipating the benefits to the public

Food And Drug Administration Science Advisory Board Meeting - Nov CONCLUSION THE PHARMA INDUSTRY WILL FOLLOW THE SAME PATH TAKEN BY THE AIRCRAFT ENGINE INDUSTRY IN ITS BID TO MORE COST EFFECTIVE AND ABOVE ALL : MORE PROFITABLE

Food And Drug Administration Science Advisory Board Meeting - Nov FACTS The Same drivers for change are thereThe Same drivers for change are there The FDA is providing increasing support realizing the benefits to the publicThe FDA is providing increasing support realizing the benefits to the public The industry is getting the sense of “dead end” doing more of the sameThe industry is getting the sense of “dead end” doing more of the same

Food And Drug Administration Science Advisory Board Meeting - Nov HOW? There is more than one tool, but NIR is probably the most significant of them There is more than one tool, but NIR is probably the most significant of them Success will create new and improved tools, soon we will not understand how it could be otherwise Success will create new and improved tools, soon we will not understand how it could be otherwise

Food And Drug Administration Science Advisory Board Meeting - Nov WHY IS NIR SO IMPORTANT? It is the only method that provides significant chemical and physical information of the bulk of the product, not just surface It is the only method that provides significant chemical and physical information of the bulk of the product, not just surface It is the only method to allow transmission through tablets and capsules for complete bulk characterization It is the only method to allow transmission through tablets and capsules for complete bulk characterization It provides information on all ingredients, not just the active It provides information on all ingredients, not just the active

Food And Drug Administration Science Advisory Board Meeting - Nov mm Depth of penetration and collection of reflected light depends on density and wavelengths. At NIR wavelengths, depth can easily reach 4 mm and more. “Sample” size is a combination of depth and illuminated area

Food And Drug Administration Science Advisory Board Meeting - Nov WHY IS BRIMROSE AOTF-NIR SO IMPORTANT? It is fast - 30 scans/sec (excellent wavelength repeatability) It is fast - 30 scans/sec (excellent wavelength repeatability) It is extremely rugged - can drop to the floor and still operate It is extremely rugged - can drop to the floor and still operate It is dual beam for real time ratio It is dual beam for real time ratio It is full scanning to provide information on all ingredients, not just active (and process all algorithms on board) It is full scanning to provide information on all ingredients, not just active (and process all algorithms on board) It is miniaturized to do blenders (battery operated) It is miniaturized to do blenders (battery operated) It is insensitive to ambient light variations It is insensitive to ambient light variations It is backed by 21CFR11 tested software from Brimrose It is backed by 21CFR11 tested software from Brimrose

Food And Drug Administration Science Advisory Board Meeting - Nov WHY IS BRIMROSE AOTF-NIR SO IMPORTANT? THE ONLY ANALYZER THAT CAN DO THEM ALL, FROM A TO Z Incoming raw materials Incoming raw materials Fluidized beds Fluidized beds Rotating blenders Rotating blenders Tablets and capsules Tablets and capsules Vials, lyophilizers Vials, lyophilizers Spray dryers Spray dryers Blister packs Blister packs Transdermal patches Transdermal patches

Food And Drug Administration Science Advisory Board Meeting - Nov

Food And Drug Administration Science Advisory Board Meeting - Nov

Food And Drug Administration Science Advisory Board Meeting - Nov ” (400) 18” (450)

Food And Drug Administration Science Advisory Board Meeting - Nov

Food And Drug Administration Science Advisory Board Meeting - Nov