1. Manufacturing Objectives
2. Current Good Manufacturing Practice
   1. Raquires
      1. QUALITY SYSTEM & independent group to oversee quality system
      2. CHANGE MANAGEMENT SYSTEM
      3. system to monitor performance and product quality to ensure state of CONTROL
      4. CORRECTIVE ACTION AND PREVENTATIVE ACTION
      5. DOCUMENTATION of process performance
   2. first appeared in 1938 FFDCA
   3. became prevalent after KEFAUVER-HARRIS AMMENDMENTS OF 1962
3. 21 CFR (Code of Federal Regulations)
   1. part 210 - CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING< PROCESSING< PACKING< OR HOLDING OF DRUGS GENERAL
      1. contains MINIMUM cGMP to meet SAFETY IDENTITY STRENGTH QUALITY AND PURITY
      2. failure to maintain will render drug ADULTERATED
      3. .2
         1. drugs covered by cGMP
            1. pharmaceutical drugs
            2. biologics
            3. cell tissue or cellbased/tissuebased products
      4. .3
         1. ACTIVE INGREDIENT
            1. furnishes PHARMACOLOGICAL ACTIVITY
         2. COMPONENT
            1. in but MAY NOT APPEAR
         3. IN PROCESS MATERIAL
            1. any material used in fabrication
      5. .3 definitions
         1. definitions
            1. DRUG PRODUCT
            2. FINISHED DOSAGE FORM containing active drug ingredient
            3. BATCH
            4. specific quantity produced according to SINGLE MANUFACTURING ORDER
            5. LOT
            6. BATCH OR PORTION PRODUCED IN A UNIT OF TIME OR QUANTITY
            7. STRENGTH
            8. CONCENTRATION OR THERAPEUTIC ACTIVITY
            9. ACCEPTANCE CRITERIA
            10. ACCEPTED QUALITY LEVEL
            11. ASSOCIATED SAMPLING PLAN
            12. ABOVE NECESSARY FOR MAKING A DECISION TO ACCEPT OR REJECT A LOT OR BATCH
            13. REPRESENTATIVE SAMPLES
            14. NUMBER OF UNITS ACCURATELY PORTRAYS MATERIAL SAMPLE
   2. part 211 - CGMP FOR FINISHED PHARMACEUTICALS
      1. A. General Provisions
      2. B. Organization and Personnel
         1. QUALITY CONTROL UNIT
            1. approve or reject
            2. components
            3. containers closures
            4. packaging labeling
            5. raw materials
            6. in process materials
            7. final drug product
            8. including those held under contract by another company
            9. responsiblities lie between
            10. QUALITY CONTROL (QC)
            11. adequate testing/lab facilities
            12. develops, approves, refects procedures
            13. must have followed procedures
            14. QUALITY ASSURANCE (QA) functions
            15. provide evidence needed to establish confidence
            16. that quality related activities performed effectively
            17. resp. for documentation, assuring SOPs, data accuracy
         2. PERSONNEL QUALIFICATIONS
            1. EDUCATION TRAINING AND EXPERIENCE
            2. GREATEST SOURCE OF CONTAMINATION -HUMANS
      3. C. Buildings and Facilities
         1. ADEQUATE NUMBER AND SIZE
         2. GOOD PRODUCT FLOW SO AS TO AVOID MIXUPS OR CONTAMINATION
         3. ADEQUATE LIGHTING< VENTILATION AND PLUMBING
         4. ADEQUATE SEWAGE, REFUSE, WASHING, and TOILETS,
         5. SANITATION
         6. MAINTENANCE
      4. D. Equipment
      5. E. Control of Components/Drug Product Containers and Cllosures
      6. F. Production and Process Controls
      7. G. Packaging and Labeling Controls
      8. H. Holding and Distribution
      9. I. Laboratory Controls
      10. J. Records and Reports
      11. K. Returned and Salvaged Drug Products
4. ICH Q7A
   1. good manufacturing practice guide for ACTIVE PHARMACEUTICAL INGREDIENTS
      1. defines API and drug product differene
         1. when API should be under control
            1. API sources
            2. chemical synthesis
            3. natural product isolation/purification
            4. rdna or proteins from cells
5. Manufacturing in Drug Development
   1. PHASE 1
      1. does not require cGMP
      2. refine process, manufacture material for phase ii and develop process for phase II
   2. PHASE II
      1. manufacture phase III material
      2. package material for phase III
      3. QA-QC identify comparatability studies needed
      4. QA/QC approve manufacturing batch records
   3. PHASE II
      1. 3 LOTS OF PRODUCT
      2. STABILITY PROGRAM to provide 1 year of data
      3. begin validation
      4. prepare for pre approval FDA inspection
   4. MARKETING APPLICATION REVIEW
   5. POST LAUNCH
      1. approved cmcs in dna/bla
6. Manufacturing in Drug Development - 2