Basic Principles of GMP Documentation Part 2 15

Basic Principles of GMP Documentation Part 2 15 Module 12 – part 2 January 2006 | Slide 1 of 35 STOP

Documentation Labels l What must be labelled? ä Containers, equipment, premises l Label information? ä Clear, unambiguous, company format ä Intermediates and bulk products l Colours can be used, e. g. green (accepted), red (rejected) 15. 10 Module 12 – part 2 January 2006 | Slide 2 of 35 STOP

Basic Principles of GMP l Different types of labels, e. g. cleaning status, production stage, status of materials l Other types of labels? Module 12 – part 2 January 2006 | Slide 3 of 35 STOP

Basic Principles of GMP l Labels can indicate the status of materials such as "quarantine" Module 12 – part 2 January 2006 | Slide 4 of 35 STOP

Documentation Finished Product Label National legislation, but includes: l Name l Active ingredients and amounts l Batch number l Expiry date l Storage conditions, precautions if necessary l Directions for use, earnings l Name and address of manufacturer Module 12 – part 2 January 2006 | Slide 5 of 35 15. 11 STOP

Documentation Reference standards Label to include: l Name l Potency or concentration l Date of manufacture l Expiry date l Date the closure is first opened l Storage condition l Control number Module 12 – part 2 January 2006 | Slide 6 of 35 15. 12 STOP

Documentation Specifications: l Authorized, approved, signed and dated ä Starting, packaging materials and finished products: include tests on identity, content, purity, quality ä Intermediates and bulk ä Water, solvents and reagents l QC, QA or documentation centre 15. 14, 15. 15 Module 12 – part 2 January 2006 | Slide 7 of 35 STOP

Documentation Specifications and Test Procedures Specifications: l Periodic review l Compliance with current pharmacopoeia l Pharmacopoeia, reference standards and spectra available Test Procedures: l Validated (facility and equipment) before routinely used 15. 13, 15. 16 -15. 17 Module 12 – part 2 January 2006 | Slide 8 of 35 STOP

Documentation Specifications: Starting and packaging materials Include: l Name (e. g. INN) and internal code l Pharmacopoeia (if applicable) l Qualitative and quantitative requirements and limits Other data may include: l Supplier l Sampling procedure or reference l Storage conditions, precautions l Retest date Module 12 – part 2 January 2006 | Slide 9 of 35 15. 18 -15. 19 STOP

Basic Principles of GMP l What types of documents are associated with sampling of starting materials? Module 12 – part 2 January 2006 | Slide 10 of 35 STOP

Documentation Specifications: Finished products Include: l Name and code reference l Names of actives (e. g. INN) l Formula l Dosage form, package details l Reference to sampling l Qualitative and quantitative requirements and limits l Storage conditions and precautions l Shelf life Module 12 – part 2 January 2006 | 15. 21 Slide 11 of 35 STOP

Documentation Master Formulae - I l Master formula for each product and batch size l Manufacturing instructions include: ä Name of product with product reference code ä Dosage form, strength and batch size ä List of starting materials including quantities and unique reference code ä Expected final yield with acceptable limits (and intermediate yields) ä Processing location and principal equipment 15. 22 – 15. 23 Module 12 – part 2 January 2006 | Slide 12 of 35 STOP

Documentation Master Formulae - II l Manufacturing instructions - continued ä Equipment preparation (e. g. cleaning, assembling, calibrating, etc. ) ä Detailed stepwise processing instructions and checks, pre -treatments, sequence of additions, times, temperatures, etc. ä In-process control instructions and their limits ä Storage requirements and special precautions ä Any special precautions if needed Module 12 – part 2 January 2006 | Slide 13 of 35 15. 22 – 15. 23 STOP

Documentation Master Formulae - III l Authorized packing instructions for each product, pack size and type, and to include: ä Name of the product ä Dosage form, strength and method of application ä Pack size (number, weight or volume of product in final container) ä List of all packaging materials (quantities, size, types and code number) 15. 24 Module 12 – part 2 January 2006 | Slide 14 of 35 STOP

Documentation Master Formulae – IV l Packing instructions - continued ä Examples of printed packaging materials, with location of batching information ä Special precautions, including area clearance checks (before and after operations) ä Description of the packaging operation including equipment to be used ä In-process controls, with sampling instructions and acceptance limits 15. 24 Module 12 – part 2 January 2006 | Slide 15 of 35 STOP

Documentation Module 12 – part 2 January 2006 | Slide 16 of 35 STOP

Documentation Batch Processing Record – I l Record kept for each batch processed l Based on the master or specifications (e. g. copied to avoid errors) l Check suitability of area and equipment ä clear of previous products, documents, materials l Checks recorded 15. 25 – 15. 26 Module 12 – part 2 January 2006 | Slide 17 of 35 STOP

Documentation Batch Processing Records – II Information recorded during processing include: l Name of the product, batch number l Dates and times (e. g. start, major steps, completion) l Name of person responsible for each stage of production l Name of operators carrying out each step (check signatures) l Theoretical quantities for materials in the batch l Reference number and quantity of materials used in the batch 15. 27 Module 12 – part 2 January 2006 | Slide 18 of 35 STOP

Documentation Batch Processing Records – III l Main processing steps and key equipment l In-process controls carried out, person's initials, and results obtained l Yield at each stage with comments on deviations l Expected final yield with acceptable limits l Comments on any deviations from process l Area clearance check, instructions to operators l Record of activities 15. 27 Module 12 – part 2 January 2006 | Slide 19 of 35 STOP

Documentation Module 12 – part 2 January 2006 | Slide 20 of 35 STOP

Documentation Batch Packaging Records – I l For every batch or part of a batch l Based on approved packaging instructions, copied or computer generated l Before start – checks that equipment and work station suitable and clean, no previous product l Line clearance (opening) l Recorded 15. 28, 15. 29 Module 12 – part 2 January 2006 | Slide 21 of 35 STOP

Documentation Batch Packaging Records – II l Name of the product, batch number and quantity to be packed l Batch number, theoretical quantity and actual quantity of finished product l Actual quantity obtained – reconciliation l Dates and times of operation l Name of person responsible for packaging, initials of operators carrying out each step l Checks, and in-process results 15. 30 Module 12 – part 2 January 2006 | Slide 22 of 35 STOP

Documentation Batch Packaging Records – III l Details of packaging operation, including equipment and line used l Returns to store l Specimen of printed packaging materials, with batch coding approval (batch number and expiry date) l Comments on deviations from the process and actions taken and authorization l Reconciliation of packaging materials, including issues, use, returns and destruction 15. 30 Module 12 – part 2 January 2006 | Slide 23 of 35 STOP

Documentation Module 12 – part 2 January 2006 | Slide 24 of 35 STOP

Documentation Standard Operating Procedures (SOP) - I l What is an SOP? l Who is responsible for preparing SOPs? l What is the format for an SOP? l Which activities require SOPs? l Where should SOPs be stored? l Are SOPs associated with records? 15. 31 Module 12 – part 2 January 2006 | Slide 25 of 35 STOP

Documentation Module 12 – part 2 January 2006 | Slide 26 of 35 STOP

Documentation Standard Operating Procedures - II Which activities require SOPs? l Equipment and analytical apparatus: – Assembly, validation – Calibration – Internal labelling, quarantine and storage of materials – Operation – Maintenance and cleaning ä Personnel matters: • Qualification • Training • Clothing 15. 31 • Hygiene Module 12 – part 2 January 2006 | Slide 27 of 35 STOP

Documentation Standard Operating Procedures - III Which activities require SOPs? l Environmental monitoring l Pest control l Complaints l Recalls l Returned goods 15. 31 Module 12 – part 2 January 2006 | Slide 28 of 35 STOP

Documentation Standard Operating Procedures - IV l SOP and records for receiving materials ä Name of material as on delivery note ä Name and in-house code ä Date of receipt ä Supplier's and manufacturer's name ä Batch number ä Quantity and number of containers received ä State of container and other information 15. 33 Module 12 – part 2 January 2006 | Slide 29 of 35 STOP

Documentation Standard Operating Procedures - V l Other SOPs include: ä Internal labelling, quarantine and storage of materials ä Operation, maintenance, calibration and cleaning of all instruments and equipment – production and QC ä Sampling of materials ä Batch numbering systems ä Material testing at all stages of production ä Complaints, recalls 15. 31, 15. 32 Module 12 – part 2 January 2006 | Slide 30 of 35 STOP

Documentation Standard Operating Procedures - VI l Which activities require SOPs? (Continued) ä Batch release or rejection ä Maintenance of distribution records ä Equipment assembly and validation ä Maintenance, cleaning and sanitation ä Personnel recruitment, training, clothing and hygiene ä Environmental monitoring ä Pest control 15. 31 …and many more… Module 12 – part 2 January 2006 | Slide 31 of 35 STOP

Documentation Stock Control and Distribution Records l What should be recorded? l Where should records be stored? l Why are the records important? Module 12 – part 2 January 2006 | Slide 32 of 35 STOP

Documentation Group Session II l From your own experience of factory inspections, how do documentation systems in this country compare with the WHO model? l Identify gaps and reasons l What will help and/or hinder the process of eliminating these gaps? Module 12 – part 2 January 2006 | Slide 35 of 35 STOP