1. Puzzled by Your Role in cGMP? 2013 Annual GMP Training Kevin Aquino, Nancy Cary, & Kelly Danyow

2. Purpose Provide a general review of current good manufacturing practices (cGMP). Discuss the importance of following cGMPs.Provide specific information related to cGMP for each department at BBD. Review requirements for records.2 3. cGMP Review So, what are cGMPs? cGMP refers to current Good Manufacturing Practice regulations enforced by the FDA. cGMPs provide for systems to assure proper design, monitoring, and control of manufacturing processes and facilities- establish the foundation for drug quality adherence to cGMP regulations assures the SPPI of products by requiring manufacturers to control operations Includes establishing quality management systems, establishing robust procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories cGMP is sameness and consistency across processes, to ensure the mitigation of variability that can lead to lack of consistency in the quality of the product current in cGMP requires companies to use up-to-date technologies and systems cGMPs are minimum requirements- may exceed but must meet 3 4. cGMP Review Why are cGMPs important? A consumer cannot easily detect that a drug product is safe or will work Testing alone is not enough to ensure adequate quality It is important that drugs are manufactured following cGMP regulations to ensure quality is built into the product at every step Blood is a drug! The Food, Drug, and Cosmetic Act defines drugs in part as articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease" and "articles (other than food) intended to affect the structure or any function of the body of man or other animals If manufacturers do not follow cGMP regulations, the drugs it makes are considered adulterated (rendered poorer in quality). cGMP violations can lead to seizure or injunction cases even if the drugs produced are not defective. This can involve destruction of adulterated drugs in a seizure case or forced hiring of outside experts, writing new procedures, or extensive training of staff in the case of an injunction. The FDA can also bring criminal cases because of cGMP violations. 4 5. cGMP at BBD Each Department at BBD plays an important part in maintaining cGMPs throughout our organization. 21 CFR Parts 210, 211 and 606 contain current Good Manufacturing Practice for Drugs/Biologics. Addressed in Subparts 5 6. cGMP at BBDHROrganization and Personnel Each person involved in the collection, manufacture, testing, storage and distribution of blood must have the education, training, and experience (or combination) to perform assigned functions and provide assurance that SPPI of product is maintained Personnel must be adequate in number Supervisors must have adequate education, training, experience (or combination) to perform assigned functions and provide assurance that SPPI of product is maintained Personnel responsibilities- good hygiene and sanitation, appropriate PPE, free of illness that may adversely affect products Consultants must have adequate education, training, experience (or combination) Appropriate records must be maintained (Records and Reports) 6 7. cGMP at BBD Buildings and Facilities Buildings must be maintained in a clean and orderly manner and be of adequate size, construction, and location Operations performed in defined areas to prevent mix-ups Adequate lighting, plumbing, ventilation, sanitationFacilities & PurchasingControl of Components and Drug Product Containers and Closures Procedures for receipt, inspection, handling, testing, and approval or rejection of drug product components and containers Handled and stored to prevent contamination Distinctive lots and disposition (quarantined, accepted, etc.) Rotated so that oldest is used first (FIFO) Records and Reports7 8. cGMP at BBD Holding and Distribution Must have warehousing procedures, including quarantined products Products must be stored to ensure SPPI Must have distribution procedures which include inventory rotation System to easily determine distribution of products in case of recall Returned and Salvaged Products Returned products must be identified and held until determined SPPI maintained If not, products are destroyed Maintain records of returns (Records and Reports) DistributionPackaging and Label Control Examination of labeling and packing material (rejected if deemed unsuitable) Strict labeling control to prevent mix-ups Visual inspection of product and labels Expiration dating to ensure product meets SPPI Production and Process Control8 9. cGMP at BBD Equipment Appropriate in design, size, and location Cleaned/maintained at appropriate intervals Automated/mechanical/electronic equipment routinely calibratedProduction and Process Controls Yield shall be calculated All equipment must be identified Sampling of each batch must be performed (QC) Production time limits Written procedures for component preparation methods Storage temperatures and methods for controlling tempLab (Component & Processing)Laboratory Controls Determine strength prior to release Test to ensure free from microorganisms Sampling plans Identification/handling of test samples Packaging and Label Control Control of Components and Drug Product Containers and ClosuresRecords and Reports 9 10. cGMP at BBDDonor ServicesEquipmentProduction and Process Controls Written SOPS shall be maintained and followed, including: Donor suitability criteria Methods to prepare phlebotomy site to ensure a sterile product Method to relate product to donor Blood collection procedure Procedures for automated collections (plateletpheresis) Donor deferral QC for supplies used in collection processRecords and Reports Donor records- medical interview and phlebotomy, deferrals, therapeutic requests for phlebotomy, reactions, quarantine records 10 11. cGMP at BBD Production and Process Controls Deviations from procedure shall be recorded and justified Procedures for investigating adverse donor and recipient reactions Consignee notification of unsuitable blood products Identify previous donations of units that test positive for infectious diseases (look back)QCTOrganization and Personnel Must have a quality control unit with responsibility to approve or rejects components, containers, products, and production records Made up of members from multiple departments Reports and Records 11 12. cGMP at BBD Equipment Automatic, mechanical and electrical equipment A back up file of data entered into the computer or related system shall be maintainedITRecords A donor number shall be assigned to each accepted donor, which relates the unit of blood collected to that donor, to his medical record, to any component or blood product from that donors unit of blood, and to all records describing the history and ultimate disposition of these products12 13. cGMP at BBD Production and Process Controls SOPs shall include: *Criteria used to determine donor suitability, including acceptable medical history criteria *Procedures for investigating adverse donor and recipient reactions *Procedures for donor deferralsScheduling & MembershipRecords and Reports13 14. cGMP at BBD Facilities First step to assuring cGMP requirement 606.40 is met When an interest is expressed in hosting a corporate on-site blood drive, Marketing provides a checklist to ensure an adequate space can be providedMCROrganization and Personnel Responsible for providing and documenting proper training to volunteers14 15. cGMP at BBDFinanceSupports departments in meeting cGMPs throughout the organization by providing resources: Buildings and Facilities Equipment Organization and PersonnelExecutive Supports the organization in ensuring adherence to cGMPs15 16. cGMP at BBD HRA record is a document stating results achieved or providing evidence of activities performed. Each dept at BBD generates records. If it is not documented, it did not happen. Records prove we are compliant to GMP and are operating in a State of control.Finance16 17. Records Records shall be maintained concurrently with the performance of each step in the collection, processing, compatibility testing, storage and distribution of each unit of blood and blood components so that all steps can be clearly traced. All records shall be legible and indelible, and shall identify the person performing the work, include dates of the various entries, show test results as well as interpretation of the results.. And be detailed as necessary to provide a complete history of the work performed. Records include but are not limited to: Donor records Processing records- results and interpretation of all tests, component preparation, labeling Storage and distribution records- visual inspection records, disposition records, temperature records Compatibility testing records- antibody screening Quality control records- calibration, performance checks of equipment, proficiency test results Transfusion reaction reports and complaints General records- biological product deviations, maintenance records, supply and reagent records, rejected supply records 17 18. Things to Remember If documentation does not occur at the same time a step is performed, this leads to omissions on our records. To omit = to fail to doWe cant assume that undocumented work has been done! Must also identify the person performing the work and the date that the work is performed. provides traceability If documentation is not required, the space should be filled in with N/A or as indicated in form key/legend (if applicable) Legible is defined as understandable- clear to any potential reviewer. Error corrections must be made appropriately- otherwise, we lose traceability.18 19. Things to Remember When you overwrite or use white-out material, you obliterate original data, which is unacceptable. Examiner needs to see original data to determine why it was changed/modified. When in doubt- cross it out! Proper error correction= single line through/ initial and date indelible is defined as impossible to remove or permanent. We cannot use felt tip pens which may wash away, as well as pencil which is erasable- these are not indelible.19 20. Summary. 20 21. Blood Bank of Delmarva 100 Hygeia Drive Newark, DE 19713 Telephone: (302) 737-8405 Toll free: (800) 548-4009 Fax: (302) 737-8233 www.delmarvablood.org21