Supaporn Phumiamorn Division of Biological Products Materials/Standards GMP course, 17-18 Jan, 2006 Supaporn Phumiamorn Division of Biological Products เอกสารประกอบการอบรมเรื่อง หลักเกณฑ์และวิธีการที่ดีสำหรับโรงงานผลิตชีววัตถุ

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Type of materials Starting materials Packaging materials Intermediate and bulk materials Finished products Rejected and recovered materials Returned goods Recalled products Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Reagent and culture media Reference standards Waste materials Miscellaneous materials Supaporn Phumiamorn,GMP course 17-18 Jan,2006

General requirements for materials All incoming materials and finished products - quarantined after receipt - until release for use - distribution Supaporn Phumiamorn,GMP course 17-18 Jan,2006

General requirements for materials Stored - under appropriate condition -orderly fashion (batch segregation) - materials management -stock rotation (FIFO, FEFO) Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 General requirements for materials Documentation - SOPs - Records - Labels - Specifications Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Starting materials Purchasing Suppliers Consignment - integrity - delivery note - seal - supplier’s label - order Cleaned and labeled Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Starting materials Damaged containers Starting materials label: - name and internal code - batch number - status - expiry date or re-test date Sample container identified Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Starting materials Use only released material Dispensing - designated persons - written procedure - accurately weighed - clean, labeled containers Supaporn Phumiamorn,GMP course 17-18 Jan,2006 เอกสารประกอบการอบรมเรื่อง หลักเกณฑ์และวิธีการที่ดีสำหรับโรงงานผลิตชีววัตถุ

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Starting materials Independent checks - material and weight Dispensed material - kept together and labeled Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Why starting materials are so important? Because their quality can directly affect the quality of finished products Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Packaging materials Primary and printed materials: - as for starting materials purchasing, handing and control No unauthorized access Storage and transport - avoid mix-ups - issue and return: SOP Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Intermediate and bulk products Appropriate conditions Purchased: -as starting materials Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Finished products Quarantine until released Storage conditions Evaluation and documentation - product release Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Rejected and recovered materials Rejected materials - clearly marked - stored separately in restricted areas - take action rapidly Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Reprocessing - exceptional - procedure and records - batch number - additional testing Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Recovery - prior authorization - additional testing Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Recalled products and returned goods - identified -stored separately - access controlled Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Returned goods - SOP: decision regarding the fate - nature of product, storage conditions - history, time lapse - records Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Reagents and culture media Record upon receipt or preparation Reagents: - preparation in accordance with SOP - label: - concentration, shelf-life, storage conditions - signed and dated Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Culture media: - positive and negative controls Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Reference Standard Standard must be stable Sufficient standard must be available for several years Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Secondary or working standards: - appropriate checks and tests - regular intervals - based on official reference standards Supaporn Phumiamorn,GMP course 17-18 Jan,2006

WHO Expert Committee on Biological Standardization (ECBS) One of the oldest WHO committees Began as a mechanism for developing primary biological standards Meet each year in Geneva Members chosen from the Expert Advisory Panel Reports published in WHO Technical Report Series Supaporn Phumiamorn,GMP course 17-18 Jan,2006

WHO Expert Committee on Biological Standardization (ECBS) Purpose - To establish primary biological standards - To prepare written guidance on production and quality control of biological medicinal products - To develop international consensus on issues of quality, safety and efficacy related to biological products Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Biological reference materials Standard and test must be similar in composition and behave in the same way in the test system Standard does not have to be pure Standard must have potency value assigned Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Calibration System WHO: Calibration is generally achieved by parallel titration on at least six separate occasions. NCL: Calibration is routinely performed at least six times by at least two persons. (2 NCL labs + Manufacturer lab) Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Calibration of WRP for Total OPV (Measles, Mumps, Rubella) Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Parallel line assay Parallelity Linearity Response 95% confidence limit Probit analysis Dose (JE, Rabies ,Hepatitis B, Pertussis vaccines) Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Reference Standard materials assuring the uniformity of the testing results assuring the reliability of the testing results Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Waste materials and miscellaneous materials - proper and safe storage - toxic and flammable materials - separate, enclosed, as per legislation - not allowed to accumulate - collected for safe disposal - regular intervals Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Miscellaneous - rodenticides, insecticides, sanitizing materials - contamination risks Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Materials checklist Quarantine Storage condition Purchasing Labelling Use of release material Printed packaging material Purchasing of intermediate or bulk Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Materials checklist Records of the original and history of seeds/ banks and etc. Specifications for biological additives Trypsin is mycoplasma free Fetal calf serum if from BSC free animals Certificate of analysis from the supplier Records of audit of supplier Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Warehouse area Entering Sufficient capacity Good storage conditions Sanitation program Receiving and dispatch bays Quarantine areas Sampling areas Segregation Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Warehouse area Highly active and hazardous materials Handling and distribution Contanmination and cross-contamination The First Expired/First Out (FEEO) Rejected materials Narcotic Damaged items Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Warehousing and Distribution Products Quarantine Quality control Release - FIFO - FEFO Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Storage conditions Stability Monitoring - Check and record - Records - Equipment calibration Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Documentations and records SOPs and Records Written information Container’s label - Name - Lot number - Shelf life - Storage conditions Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Receipt of incoming materials Check against the relevant purchase order Uniformity Container inspection Record should be retained for each delivery Sampling Quarantine and batch segregation Written release or rejection Rejected materials cannot be used Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Stock rotation and control Comprehensive records Periodic stock reconciliation Significant stock discrepancies Re-close and reseal Damaged containers Outdate materials Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Dispatch and transport Integrity Special care for dry ice Delivery order Rules for dispatch The outside container Monitor conditions during transportation Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 Warehouse check list Identification of all customers Records of storage: time, temperatures Records of date, quantity, mode of packaging Distribution to customer SOPs for storage of released products Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 SOPs for warehousing SOPs for shipping, final transit conditions and storage Validation and monitoring of shipping methods Recalled Maintenance of records for 2 years beyond Expiry date Supaporn Phumiamorn,GMP course 17-18 Jan,2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 References WHO,1997. Joint training on GMP for biological products in Thailand, 2-11 September, 1997 Chung Keel Lee, 2003. GMP and related topics, 13-15 October, 2003. Chung Keel Lee, 2004. Current GMP for biological products and its practical implementation, 22-23 March, 2004. FDA and WHO, 2004. GMP inspection workshop, 21-29 June, 2004. Supaporn Phumiamorn,GMP course 17-18 Jan,2006