Chemical Development
Capabilities Presentation
Centrally Located on America’s North Coast

43-acre site near Cleveland, Ohio

                                    Three m...
Focused on Our Clients’ Needs

• Established in 1986
• Annual growth rate of 20% for last four years
• Completed projects ...
Our People – Experienced, Motivated, Collaborative


  • Total company staff of 300
  • >35% with Ricerca for >10 years
  ...
Primary Services

Drug Development Biology     Medicinal Chemistry
• Animal Models of Disease   Chemical Development
• Dru...
Chemical Development – Our People

              Motivated professionals working in
        interdisciplinary teams to exe...
Chemical Development – Our Strengths

• Organic Chemistry – expert in established reactions
  with the ability to rapidly ...
Chemical Development – Our Services

Process Chemistry
• Chemical route evaluation & selection
• Process research
• Proces...
Chemical Development – Our Services

Analytical Chemistry
• Methods development and validation – phase
  appropriate
• Ref...
Chemical Development – Our Services

API Preparations & Manufacturing
• API preparation for preclinical use
• API preparat...
Putting It All Together – Project Management

•   Multi-disciplinary team led by Project
    Leader
•   Project Leader is ...
Drug Development Program - Phase I
              Technology Input – Discovery Route
Preclinical to Phase I
   •   Chemical...
Drug Development Program - Phase II

Phase II - API Chemical Development and Supply
•   Applied process research and devel...
Drug Development Program – Phase III

Phase III – Validation and API Supply
•   Process Justification – critical process p...
Our Quality System

•   Full compliance with the ICH Q7A Harmonized
    Guidelines for current Good Manufacturing
    Prac...
Our Tools – Process Chemistry

Process Research Laboratories
   •   General purpose – mg to kg
   •   Processing scale - u...
Our Tools – Process Chemistry




   Radiochemistry




                            cGMP Kilo Lab
Our Tools – Analytical Chemistry

FDA-, cGMP-, GLP-, ICH-, EPA-, and OPECD- Compliant

•   Atomic spectroscopy   AA, ETAAS...
Our Tools – Analytical Chemistry




Automated XRD

                                     HPLC Systems




                ...
Our Tools – Plant Facility
        Three-story cGMP facility
        • Batch and continuous processing
        • Isolation...
Our Tools – Plant Reaction Systems
                    Multipurpose Pilot Plants

Reaction Systems
• 17 reactors
• Total c...
Our Tools – Processing Support Equipment

Support Equipment
• Separations (Liquid/Liquid)
  - Batch distillation – custom
...
Our Tools – Plant Facility

                                 400-Liter GLS Reaction System




Shelf Dryer in Finishing Su...
A Proven Track Record


First Pharma ceutical P roject               19 87
Pharma ceutical P rojects                    > ...
The Benefits We Bring

•   Chemistry – Engineering synergy results in
    development of robust practical process
•   Expe...
Project Profile - Background

•   Young biotech company
•   New indication for licensed-in compound
•   Small molecule
•  ...
Project Profile - Outcome

•   Original process benchmarked and used to
    prepare initial API supply
•   Process changes...
Project Profile – Outcome

•   Improved process successfully demonstrated at
    400- liter scale
•   Manufacturing cost r...
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Chemical Development \'09

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Overview of Ricerca chemical development capabilities.

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Transcript of "Chemical Development \'09"

  1. 1. Chemical Development Capabilities Presentation
  2. 2. Centrally Located on America’s North Coast 43-acre site near Cleveland, Ohio Three main buildings: • 260,000 square feet • 125 well-equipped labs • 4 cGMP kilo labs • 6 general-purpose kilo labs • Plant production facility • 8 isolation/finishing suites • 43 animal rooms - 7 BSL2 Rated • Cell culture suite • Advanced LC/MS/MS lab
  3. 3. Focused on Our Clients’ Needs • Established in 1986 • Annual growth rate of 20% for last four years • Completed projects for >450 clients ─ virtual biotech to global pharma • Contributed to 8% of all US INDs filed by biotechnology companies in 2007 • >100 APIs produced – KL and plant scale • >200 quality audits passed • Excellent process safety and environmental compliance record
  4. 4. Our People – Experienced, Motivated, Collaborative • Total company staff of 300 • >35% with Ricerca for >10 years • Chemical Development (CD) staff of 93 • Average industrial experience in CD is >13 years • >50% of technical staff hold advanced degrees
  5. 5. Primary Services Drug Development Biology Medicinal Chemistry • Animal Models of Disease Chemical Development • Drug Safety Assessment • Process Research & - Toxicology Development - Safety Pharmacology • Scale-up & Demonstration • Pharmacokinetics • Analytical Methods • Drug Metabolism Development & Compound Characterization - In vitro and In vivo • API Preparation • Bioanalytical Methods • Technology Transfer Development & Sample Processing • Regulatory Support • Regulatory Support • Project Management • Project Management
  6. 6. Chemical Development – Our People Motivated professionals working in interdisciplinary teams to execute your project Analytical Process Process Development Chemistry Chemistry and Engineering PhD 7 15 1 MS 21 7 3 BS 5 4 4 Technician 5 Operator 21 Total 33 31 29 Years of Industrial > 13 > 13 > 22 Experience
  7. 7. Chemical Development – Our Strengths • Organic Chemistry – expert in established reactions with the ability to rapidly master new innovative technologies • Analytical Chemistry – diversified analytical expertise applied to solve problems and support development programs • Process Development & Scale-up – rapid conversion of a discovery route into a commercially-viable process with demonstration in the pilot plant • Custom Processing – rapid production of products to support the development program
  8. 8. Chemical Development – Our Services Process Chemistry • Chemical route evaluation & selection • Process research • Process justification and robustness testing Process Development & Engineering • Process development • Scale-up & demonstration • Process optimization and cost analysis • Process validation • Technology transfer
  9. 9. Chemical Development – Our Services Analytical Chemistry • Methods development and validation – phase appropriate • Reference standard characterization • Impurity & metabolite ID and characterization • Forced degradation studies • Photostability studies • Storage stability studies • Salt screening and selection • Polymorph identification & characterization • API release testing for research & commercial use
  10. 10. Chemical Development – Our Services API Preparations & Manufacturing • API preparation for preclinical use • API preparation for clinical use using cGMP controls • Commercial API manufacturing – selective basis • Preparation of reference standards, impurities, & metabolites • Radiolabeled synthesis – using cGMP controls when needed Regulatory Support • CMC section preparation for IND filing • Regulatory consultation
  11. 11. Putting It All Together – Project Management • Multi-disciplinary team led by Project Leader • Project Leader is key client interface – your “Go To” person • Direct and frequent communication – “the good, the bad, and the ugly” • Direct access to team members • Rapid and flexible response to project scope changes
  12. 12. Drug Development Program - Phase I Technology Input – Discovery Route Preclinical to Phase I • Chemical route assessment • Chemical route modification • API method development – purity (stability-indicating), impurities, residual solvents, counter-ion, process residues • API preparation and characterization for use in toxicology studies • Phase I process research – safety, reliability, scale-ability • API preparation and characterization for Phase I clinical trials • API physical and chemical characterization • CMC documentation package preparation IND Granted – Phase I Trials Successful!
  13. 13. Drug Development Program - Phase II Phase II - API Chemical Development and Supply • Applied process research and development - Supported by economic modeling - Establish commercially-viable API production process • API process scale-up and demonstration • API methods refinement • API preparation and characterization for Phase II clinical trials • API production technology documentation • Program is customized to meet specific client requirements Phase II Trials Successful!
  14. 14. Drug Development Program – Phase III Phase III – Validation and API Supply • Process Justification – critical process parameters and critical quality attributes • Analytical Methods Validation for commercial use • Process Validation • NDA Lot Production – 3 Lots • NDA Lot Storage Stability Program – 3 Lots • Process Documentation for NDA submission Commercial Launch and Production
  15. 15. Our Quality System • Full compliance with the ICH Q7A Harmonized Guidelines for current Good Manufacturing Practices (GMPs) for Active Pharmaceutical Ingredients (APIs) • Excellent compliance record – passed audits by >200 clients and US FDA • Passed first US FDA PAI in late 2007 • System incorporates best practices developed by interaction with our diverse client base • Our challenge – balance compliance, cost, and timing
  16. 16. Our Tools – Process Chemistry Process Research Laboratories • General purpose – mg to kg • Processing scale - up to 12 liters • Pressure range: FV to 50 psig • Temp range: -78 to +200 ºC Radiochemistry Labs - 4 • Licensed for 3H, 14C, 32P, 35S, 131I, 125I, 99Tc, 36Cl cGMP Kilo Labs - 4 • HEPA-filtered air system • Processing scale to 50 liters • Temperature range: -78 to +200 ºC • Dedicated single project use General Purpose Kilo Labs - 6
  17. 17. Our Tools – Process Chemistry Radiochemistry cGMP Kilo Lab
  18. 18. Our Tools – Analytical Chemistry FDA-, cGMP-, GLP-, ICH-, EPA-, and OPECD- Compliant • Atomic spectroscopy AA, ETAAS, ICP • Chromatography GC, LC, IC, GPC • Microscopy Optical, Polarized, Hot-stage, Raman • Microbiology LAL, Bioburden • Molecular FTIR, FT-NMR, GC/MS, Raman LC-MS/MS, LC-MS, UV • Thermal analysis DSC, TGA, HSM, XRD • X-ray analysis Combinatorial, Temp, Humidity • Physical testing Particle size, Density, pka, logP, logD • Water analysis KF, DVS, Static vapor • Solubility Tecan, Safire, Nephelometric
  19. 19. Our Tools – Analytical Chemistry Automated XRD HPLC Systems NMR Center
  20. 20. Our Tools – Plant Facility Three-story cGMP facility • Batch and continuous processing • Isolation/finishing rooms • Process and IPC testing labs
  21. 21. Our Tools – Plant Reaction Systems Multipurpose Pilot Plants Reaction Systems • 17 reactors • Total capacity = 17,000 liters • Sizes from 40 to 3,000 liters • MOC – GLS and 316SS • FV to 400 psig • - 55 to +165°C
  22. 22. Our Tools – Processing Support Equipment Support Equipment • Separations (Liquid/Liquid) - Batch distillation – custom design - Thin-film/wiped film evaporator • Separations (Solid/Liquid) - Centrifuges - Pressure/vacuum filters • Flash Chromatography - 40-kg SG cartridge • Drying - Rotary cone - Vacuum shelf
  23. 23. Our Tools – Plant Facility 400-Liter GLS Reaction System Shelf Dryer in Finishing Suite
  24. 24. A Proven Track Record First Pharma ceutical P roject 19 87 Pharma ceutical P rojects > 220 APIs P roduced > 100 API Int ermedia tes Produce d > 30 APIs a nd Interme diate s Produced > 5 ,50 0 kgs Technology Transfers 18 Most Complex API Project 16 chemical steps 1 chiral center – 100 kilograms
  25. 25. The Benefits We Bring • Chemistry – Engineering synergy results in development of robust practical process • Experienced, motivated, and collaborative staff that excels at executing challenging projects • Continuity of API supply – preclinical to commercial production – all at one site • Collaborative partnership approach • Proven capability to develop and transfer technology to CMO (if needed) • Commitment to quality and continuous improvement
  26. 26. Project Profile - Background • Young biotech company • New indication for licensed-in compound • Small molecule • Limited process and analytical information • Chemical route selected • Process consisted of 4 reaction/isolation segments • Project requirements: - Supply API for clinical program - Develop manufacturing process
  27. 27. Project Profile - Outcome • Original process benchmarked and used to prepare initial API supply • Process changes identified, tested, and reduced to practice • Significant process changes were: - two processing segments combined into one - cycle time for limiting step reduced by 5X - productivity of limiting step increased by 4X Net effect - throughput increased by 3X
  28. 28. Project Profile – Outcome • Improved process successfully demonstrated at 400- liter scale • Manufacturing cost reduced by 50% • API supplied for clinical program through Phase IIB • Complete analytical methods package developed • Technology transferred to commercial partner • Technology successfully demonstrated at 8,000-liter scale • Product launched worldwide in 2003

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