6.1 Documentation.pptxxxxxxxxxxxxxxxxxxx
- 2. 1. To review general requirements for documents 2. To review specific requirements for each document 3. To consider current issues applicable to a facility
- 3. Good documentation is an essential part of the QA system Should exist for all aspects of GMP Purpose of documentation Defines specifications and procedures for all materials and methods of manufacture and control Ensures all personnel know what to do and when to do it Ensures that authorized persons have all information necessary for release of product
- 4. Purpose of documentation (cont.) Ensures documented evidence, traceability and provides records and audit trail for investigation Ensures availability of data for validation, review and statistical analysis Design and use Depends upon manufacturer Some documents combined into one, sometimes separate
- 5. Documents should be Designed Prepared Reviewed Distributed with care Carefully controlled Comply with Marketing Authorization
- 6. Design of documentation important Look at the “Style” of the document Instructions in the imperative Short sentences preferred to long sentences Approval of documentation Approved, signed and dated by appropriate responsible persons No document should be changed without authorization and approval
- 7. Contents of documents should be clear (easy to understand) and include, e.g. Title, nature, objective or purpose Layout in orderly fashion Easy to be filled in and checked Clear and readable – including copies made No errors if master documents are copied for working documents
- 8. Documentation control Regular review of documents Kept up to date (current) - amended Superseded documents removed and not used Distribution and retrieval of documentation Retention time for superseded documents
- 9. Data entry Clear, readable and indelible Design to allow for sufficient space for entries Changes to entries: signed, dated and reason given original entry still readable Entries at the time of action All significant actions recorded – traceable
- 10. Data entry (cont.) Electronic data processing systems, photographic systems or other reliable means Systems require SOPs and records Accuracy of records checked Authorized persons - access and changes Password controlled Entries checked
- 11. Data entry (cont.) Batch records stored electronically: Protected Back-up transfer, e.g. magnetic tape, microfilm, paper print-outs Records kept 1 year after expiry date of product Data readily available during retention period
- 12. Labels Specifications and testing procedures Master formulae and instructions Batch processing and batch packaging records Standard Operating Procedures (SOPs) Records Stock control and distribution records Other documents …
- 13. Photographs can be documents provided they are properly authorised and controlled
- 14. Flow charts provide substantial information at a glance
- 15. What must be labelled? • Containers, equipment, premises • Intermediates and bulk products Label information? •Clear, unambiguous, company format Colours can be used, e.g. green (accepted), red (rejected)
- 16. Different types of labels, e.g. cleaning status, production stage, status of materials Other types of labels?
- 17. Labels can indicate the status of materials such as "quarantine"
- 18. National legislation, but includes: Name Active ingredients and amounts Batch number Expiry date Storage conditions, precautions if necessary Directions for use, warnings Name and address of manufacturer
- 19. Label to include: Name Potency or concentration Date of manufacture Expiry date Date the closure is first opened Storage condition Control number
- 20. Authorized, approved, signed and dated Starting, packaging materials and finished products: include tests on identity, content, purity, quality Intermediates and bulk Water, solvents and reagents QC, QA or documentation centre
- 21. • Documented Specifications Are required for • Starting and packaging materials • Finished products
- 22. Specifications: Periodic review Compliance with current pharmacopoeia Pharmacopoeia, reference standards and spectra available Test Procedures: Validated (facility and equipment) before routinely used
- 23. Master formula for each product and batch size Manufacturing instructions include: Name of product with product reference code Dosage form, strength and batch size List of starting materials including quantities and unique reference code Expected final yield with acceptable limits (and intermediate yields) Processing location and principal equipment
- 24. Manufacturing instructions – continued Equipment preparation (e.g. cleaning, assembling, calibrating, etc.) Detailed stepwise processing instructions and checks, pre-treatments, sequence of additions, times, temperatures, etc. In-process control instructions and their limits Storage requirements and special precautions Any special precautions if needed
- 25. Authorized packing instructions for each product, pack size and type, and to include: Name of the product Dosage form, strength and method of application Pack size (number, weight or volume of product in final container) List of all packaging materials (quantities, size, types and code number)
- 26. Packing instructions – continued Examples of printed packaging materials, with location of batching information Special precautions, including area clearance checks (before and after operations) Description of the packaging operation including equipment to be used In-process controls, with sampling instructions and acceptance limits
- 27. Record kept for each batch processed Based on the master or specifications (e.g. copied to avoid errors) Check suitability of area and equipment clear of previous products, documents, materials Checks recorded
- 28. Information recorded during processing include: Name of the product, batch number Dates and times (e.g. start, major steps, completion) Name of person responsible for each stage of production Name of operators carrying out each step (check signatures) Theoretical quantities for materials in the batch Reference number and quantity of materials used in the batch
- 29. Main processing steps and key equipment In-process controls carried out, person's initials, and results obtained Yield at each stage with comments on deviations Expected final yield with acceptable limits Comments on any deviations from process Area clearance check, instructions to operators Record of activities
- 30. For every batch or part of a batch Based on approved packaging instructions, copied or computer generated Before start – checks that equipment and work station suitable and clean, no previous product Line clearance (opening) Recorded
- 31. Name of the product, batch number and quantity to be packed Batch number, theoretical quantity and actual quantity of finished product Actual quantity obtained – reconciliation Dates and times of operation Name of person responsible for packaging, initials of operators carrying out each step Checks, and in-process results
- 32. Details of packaging operation, including equipment and line used Returns to store Specimen of printed packaging materials, with batch coding approval (batch number and expiry date) Comments on deviations from the process and actions taken and authorization Reconciliation of packaging materials, including issues, use, returns and destruction
- 33. What is an SOP? Who is responsible for preparing SOPs? What is the format for an SOP? Which activities require SOPs? Where should SOPs be stored? Are SOPs associated with records?
- 34. Which activities require SOPs? Equipment and analytical apparatus: – Assembly, validation – Calibration – Internal labelling, quarantine and storage of materials – Operation – Maintenance and cleaning Personnel matters: oQualification oTraining oClothing oHygiene
- 35. Which activities require SOPs? Environmental monitoring Pest control Complaints Recalls Returned goods
- 36. SOP and records for receiving materials Name of material as on delivery note Name and in-house code Date of receipt Supplier's and manufacturer's name Batch number Quantity and number of containers received State of container and other information
- 37. Other SOPs include: Internal labelling, quarantine and storage of materials Operation, maintenance, calibration and cleaning of all instruments and equipment – production and QC Sampling of materials Batch numbering systems Material testing at all stages of production Complaints, recalls
- 38. Which activities require SOPs? (Continued) Batch release or rejection Maintenance of distribution records Equipment assembly and validation Maintenance, cleaning and sanitation Personnel recruitment, training, clothing and hygiene …and many more…
- 39. Stock Control and Distribution Records What should be recorded? Where should records be stored? Why are the records important?
- 40. Data Integrity a Hot Topic in EU and US FDA - Draft guidance on Data integrity and Compliance with cGMP issued April 16 MHRA - Draft guidance on GXP Data Integrity Definitions and Guidance for Industry July 16 PIC/S – Draft guidance on Good practices for Data Management and Integrity in Regulated GMP/GXP Environments Aug 16 EMA extended the Q and A section of the GMP webpage with an additional 23 questions and answers regarding Data Integrity
- 42. • Data integrity enables good decision-making by pharmaceutical manufacturers and regulatory authorities • It is a fundamental requirement of the pharmaceutical quality system described in EU GMP chapter 1, applying equally to manual (paper) and electronic systems. • Promotion of a quality culture together with implementation of organisational and technical measures which ensure data integrity is the responsibility of senior management. • It requires participation and commitment by staff at all levels within the company, by the company’s suppliers and by its distributors. • Senior management should ensure that data integrity risk is assessed, mitigated and communicated in accordance with the principles of quality risk management. • The importance of data integrity to quality assurance and public health protection should be included in personnel training programmes. Data Integrity – a foundational requirement
- 43. • The template (blank) forms used for manual recordings may be created in an electronic system (Word, Excel, etc.). • The corresponding master documents should be approved and controlled electronically or in paper versions. • The following expectations should be considered for the template (blank) form: have a unique reference number (including version number) and include reference to corresponding SOP number should be stored in a manner which ensures appropriate version control if signed electronically, should use a secure e-signature • The distribution of template records (e.g. ‘blank’ forms) should be controlled. • The following expectations should be considered where appropriate, based on data risk and criticality: enable traceability for issuance of the blank form by using a bound logbook with numbered pages or other appropriate system. For loose leaf template forms, the distribution date, a sequential issuing number, the number of the copies distributed, the department name where the blank forms