1. Current Good Manufacturing Practices (cGMP’s)

2. Biotechnology using living cells and materials produced by cells to create pharmaceutical, diagnostic, agricultural, environmental, and other products to benefit society.

3. How Do Biotech Products Differ from Chemical Drugs? Produced from living cells Large, complex molecules Extremely sensitive to their environment –Production –Storage –Manufacturing changes

4. What Does FDA Do? Approve products –Safety –Effectiveness –Risk/Benefit determination Monitor drug performance Monitor investigational studies Inspect manufacturers Inform physicians and consumers

5. Biotechnology Companies make products

6. CEO – Chief Executive Officer COO – Chief Operations Officer CIO – Chief Information Offices Vice President of Research and Development Vice President of Medical Affairs VP Sales and Marketing Organizational Structure

7. Operations

8. Operations responsibilities This is where cGMP comes into play

9. So What is cGMPs?

10. What are cGMP’s Designed To Do? Protect consumers from adulterated product Protect consumers from products that do not contain what is claimed on the label Provide consistent industry-wide requirements Ensure quality of product not safety or efficacy of dietary ingredients

11. Why have cGMP’s? Congress saw need by authorizing Food, Drug, and Cosmetic Act gives authority for cGMP’s Product recalls and independent lab testing demonstrate need for cGMP’s Industry and consumers support cGMP’s

12. What caused the need for cGMP’s? Product recalls and independent laboratory testing demonstrate need for CGMP’s: Poor sanitation--bacterial contamination Ingredient often either Superpotent or Subpotent Contaminated with prescription drugs

13. How are cGMPs developed Considerations and Process: How products are manufactured (e.g. tablets, capsules, powders, liquids) Unique properties of dietary ingredients and dietary supplements (e.g. vitamins, minerals, botanicals) Desire for clear, enforceable regulation Considered the estimated costs and benefits

14. General Provisions cGMP should apply to activities associated with –manufacturing –packaging –holding –distributing Manufacturer would need to comply with requirements applicable to operations performed

15. Components of a cGMP Personnel –qualified employees –employees must have training and experience to perform assigned duties –disease control, and hygienic practices –assign qualified supervisors to oversee implementation of cGMP’s

16. Components of a cGMP Physical plant internal environment –design and construction ceilings, floors, and walls that are easily cleaned and maintained separate areas or systems for specific operations to avoid mixups screening to keep out pests –maintenance and sanitation –water meets EPA drinking water requirements –plumbing, bathroom, lighting, ventilation, trash requirements to prevent contamination

17. Components of a cGMP Equipment and utensils –design or select equipment that will meet pre-established specifications –maintain, clean, and sanitize –calibrate, inspect, or check to ensure proper performance –ensure that equipment functions as intended

18. Components of a cGMP Production and process controls –quality control unit –master manufacturing and batch production records –specifications for incoming, in-process, and final product and –testing final product or incoming and in- process materials

19. Considerations of a cGMP Holding and Distributing –to ensure that identity, purity, quality, strength, and composition are not adversely affected hold and distribute under –appropriate conditions of temperature, humidity, and light –conditions that do not lead to mixup, contamination, or deterioration

20. Components of a cGMP Records and Recordkeeping-- performance records for –calibration, master manufacturing and batch production, and consumer complaints –keep for 3 years beyond date of manufacture of batch and –FDA access to records when requested

21. Production and Process Controls System of production and process controls Quality control unit Manufacturing operations Holding and distributing Recordkeeping

22. Production and Process Controls System of production and process controls –specifications –testing –monitoring, material review, disposition decision –master manufacturing record –batch production record

23. Production and Process Controls Quality control unit: One or more persons to –approve or reject procedures, specifications, controls, tests, and deviations or modifications –approve or reject materials received and product manufactured, packaged, and labeled –review and approve master manufacturing and batch production records

24. Production and Process Controls Master manufacturing record (cont.) Prepare and follow Include list of components Specifications where control is necessary to prevent adulteration Weight or measure for each component Instructions for adding, mixing, sampling, testing Expected yields Specifications for packaging and label to use Keep master manufacturing record

25. Production and Process Controls Batch production record Accurately follows master manufacturing record Includes quality control unit review and approval of –batch production record –cross reference of receiving and batch production records –any material review and disposition decision –reprocessing –release for distribution Keep for 3 years beyond date of batch production

26. Batch Records FDA Requirement cGMP requirement QSR requirement ISO requirement Failing to do so can get you into a heap of trouble! Used to ensure consistent product

27. Batch Record: Record Keeping What are some record keeping requirements? –Black ink –No white out –Single line, date, initial –No blanks, N/A any lines which do not apply –Legible

28. Review and Storage of Batch Record Mfg sign off on Mfg documents QC signs off on QC documents and Mfg documents Quality Assurance signs off on the batch record and their signature indicates they have reviewed all documents in the record including Mfg., QC, and any other document

29. Production and Process Controls Manufacturing operations –design or select to ensure specifications achieved –conduct in accordance with sanitation principles –take precautions to prevent contamination

30. Production and Process Controls Precautions would include –protecting against growth of microorganisms and potential for contamination –washing or cleaning components that contain soil or other contaminants –preventing the growth of microorganisms and decomposition –preventing against inclusion of foreign material –identifying all processing lines and major equipment used during manufacturing to indicate their contents, batch/lot number, and when necessary phase of manufacturing

31. Laboratory Operations Establish and follow laboratory controls Use adequate facilities in-house or from outside sources to perform testing and examinations Keep laboratory test and examination records