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Semelhante a Documentation control - principles of GMP
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Documentation control - principles of GMP
- 1. BASIC PRINCIPLES OF GMP Documentation 1 PREPARED BY:AJAY KUMAR
- 2. DOCUMENTATION o Documentation is an essential part of QA and relates to all aspects of GMP. o The pharmaceutical industry must have a good document framework (infrastructure). o It is important for a manufacturer to get the documentation right in order to get the product right. The objective of documentation is to review – General requirements for documents – Specific requirements for each document 2
- 3. What is being made? Most of us when attempting a task need some sort of documentation. Documentation 3
- 4. And if the drawing is wrong! Documentation 4
- 5. OBJECTIVES OF DOCUMENTATION To ensure that there are specifications for o All materials o Methods of manufacture o Methods of control o All personnel know what to do and when to do o Authorized persons have all information o Provide audit trail • Purposes for documents: • Define specifications for materials and for methods of manufacture and control. • Ensure that everyone concerned with manufacture and QC knows what to do, how and when to do it. • Allow decisions to be taken on batch release. • Provide an audit trail, which is particularly important in the case of suspect batches. 5
- 6. GENERAL PRINCIPLES – I Documents should be Designed Prepared Reviewed Distributed with care Design of documentation 6
- 7. GENERAL PRINCIPLES – II Inspectors should look at the “Style” of the document Necessary Instructions Short sentences Not long sentences 7
- 8. GENERAL PRINCIPLES – III Approval of documentation Approved, signed & dated by authorized persons No document should be changed without authorization Any alteration made to a document should be signed and dated; The alternation should permit the reading of the original information. Where appropriate the reason for the alternation should be recorded. 8
- 9. GENERAL PRINCIPLES – IV Distribution of documents needs to be carefully controlled in order to ensure that Up-to-date version of documentation Electronically or photographically recorded data Unauthorized photocopying of original documents should be actively discouraged Require system for regular revision Document register is needed and requires proper maintenance 9
- 10. VARIOUS TYPES OF DOCUMENTATION Labels, specifications and master formulae Batch processing and batch packaging records Standard operating procedures Stock and distribution records Water quality 10
- 11. LABELS What must be labelled? What must be on the label? Who has responsibility for labelling? Two classes of labels. Finished product labels, which must meet national drug regulatory authority requirements as specified in the marketing authorization. Then there are the labels used within the factory to control processes. Labels are required for all containers of materials, whether for starting materials, intermediates or finished products; 11
- 12. LABELS Sample label must be preserved Labels for all process equipment and for premises that are in use for manufacturing. Labels should be clear and unambiguous. It is advisable to use colours to indicate status (quarantine, accepted, rejected, cleaned or dirty). For other purpose the company can use their own labelling system but for finished products, there is a national requirement. 12
- 13. LABELS Responsibility for labelling varies with company practice, but the process is generally overseen and controlled by the QC department. QC staff are responsible for issuing status labelling when a material has been approved or rejected. The responsible production and/or QC staff should sign labels stating that equipment is clean and available for use. Reference standards (both primary and secondary) must be appropriately labelled and the issue of these must be controlled. 13
- 14. SPECIFICATIONS AND TEST PROCEDURES Starting and packaging materials Intermediates and bulk products Finished products Test procedures must be validated or verified for the available facilities before they are used for routine testing. Compendial methods need to be verified. Specifications will include tests for identity, content purity and quality. 14
- 15. SPECIFICATIONS AND TEST PROCEDURES Specifications should be dated and authorized. The responsibility for their issue and maintenance rests with the QC department. Update the documents occasionally in line with national compendiums or the company's requirements. Written specifications are required for all starting and packaging materials including water in all its various standards. 15
- 16. SPECIFICATIONS AND TEST PROCEDURES Document should contain the following: International name and internal code reference Pharmacopoeia reference if appropriate Test parameters and acceptance criteria Details of supply, testing methodology and storage conditions. For packaging materials, there should be reference to compatibility with the drug. For all materials, the frequency of retest should be specified. 16
- 17. SPECIFICATIONS AND TEST PROCEDURES If intermediates or bulk products are either purchased or dispatched, then they will need a specification. Specification is required if the data of these materials are going to be used in the assessment of the finished product. They will be similar to the specification for the starting material or finished product, as appropriate. 17
- 18. SPECIFICATIONS AND TEST PROCEDURES For finished products, the specification should include the following information: Name and internal code reference Name of the active ingredients The formula (or a reference to it) Description of dosage form and packaging Sampling and testing methodology Test parameters and acceptance criteria Storage conditions Shelf-life. Specifications and test procedures will be used by the QC department and are generally located in the laboratories. 18
- 19. MASTER FORMULAE I Manufacturing instructions Name of product with reference code Dosage form, strength and batch size Full list of materials- quantities; unique reference code Expected final yield with acceptable limits (plus intermediate yields) Processing location and equipment 19
- 20. MASTER FORMULAE II There must be a formally approved master formula for each product that is manufactured, in each batch size. The information includes the following: Equipment preparation methodology Stepwise processing instructions Details of in-process controls with instructions for sampling and acceptance limits Storage requirements and special precautions. 20
- 21. MASTER FORMULAE III Packing instructions It covers packaging rather than manufacturing Name of the product Dosage form, strength and method of administration Final Pack size (number, weight or volume of product in finished pack) List of all packaging materials (quantities, size and code number) 21
- 22. MASTER FORMULAE - IV Packing instructions - continued Batching information Special precautions, including area clearance checks Description of the packaging operation In-process control checks, with sampling instructions and acceptance criteria These documents are used as references in the development of processing records. They should be located in development, quality control and production departments. 22
- 23. MASTER FORMULAE - IV Packing instructions – continued The master formula is frequently used as the master batch-processing document. It is often photocopied to provide the individual batch- processing document. Whatever method is used, it must ensure that there can be no transcription error. The batch-processing document is never a hand-written copy. The same method can be used to prepare the batch packaging document. 23
- 24. BATCH PROCESSING RECORDS - I A batch processing record is required for each batch of material produced. The review of this document is a critical part of the batch release process. A master document should be prepared for each batch size that will be manufactured. It will be taken from the relevant parts of the master formula as discussed previously. The first step in this document must be the area clearance check. 24
- 25. BATCH PROCESSING RECORDS - I This is a record of the previous product and batch processed in the area and a confirmation that all the material and documentation relating to that batch has been removed. It is also confirmation that all the cleaning has been carried out correctly. This check must always be documented. It is both a detailed instruction to the operator of the activities that must be carried out during manufacturing and a record that these activities have been carried out. 25
- 26. BATCH PROCESSING RECORDS - I It should be filled in at the time that processing takes place. Critical activities require a check signature from a second person (either from production or QC as appropriate) to confirm that the information recorded is accurate. The information required in the batch processing record includes: Name of the product Batch number Dates and times for major steps in the process Name of person responsible for each stage of production Name of operators carrying out each step and check signatures if required Theoretical quantities for materials in the batch 26
- 27. DOCUMENTATION BATCH PROCESSING RECORDS – II Main processing steps and key equipment In-process controls carried out, 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 27
- 28. DOCUMENTATION Batch Packaging Records – III Name of the product, batch number and quantity to be packed Batch number, theoretical quantity and actual quantity of finished product Reconciliation calculations, dates and times of operation Name of person responsible for packaging, initials of operators carrying out each step Checks made and results obtained 28
- 29. DOCUMENTATION Batch Packaging Records - IV Details of packaging operation, including equipment and line used Returns to store Specimen of printed packaging materials, with batch coding Comments on deviations from the process and actions taken Reconciliation of packaging materials, including returns and destruction Area clearance check Product variables Record of activities and check signatures 29
- 30. DOCUMENTATION Standard Operating Procedures - I Who is responsible for SOPs? Where should SOPs be stored? 30
- 31. Standard Operating Procedures - II Which activities require SOPs? Receipt of all material deliveries Internal labelling, quarantine and storage of materials Operation, maintenance and cleaning of all instruments and equipment Sampling of materials Batch numbering systems Material testing at all stages of production 31 Documentation
- 32. DOCUMENTATION STANDARD OPERATING PROCEDURES - III Which activities require SOPs? - continued Batch release or rejection. Maintenance of distribution records Equipment assembly and validation Calibration and operation of analytical apparatus Maintenance, cleaning and sanitation Personnel recruitment, training, clothing and hygiene Environmental monitoring 32
- 33. DOCUMENTATION Stock Control and Distribution Records What should be recorded? Where should records be stored? Why are the records important? 33
- 34. DOCUMENTATION Water Quality Manual Full details of design of system, operation and maintenance Details of testing requirements 34
- 35. Finish 35
Notas do Editor
- This module deals with the very important topic of documentation. It is a half to one-day session (depending on the participants ability and experience) divided into 2 roughly equal parts: In each half, there will be 30 - 45 minutes of presentation, 45 minutes discussion in groups and 30 minutes feedback to the whole group. There will be one test and discussion (40 minutes) covering the whole module that will be taken at the end.
- There are three objectives for this session: 1. We are going to start by looking at the general requirements for all documents and to review the types of documents listed in the WHO GMP text. 2. Then we will look at the specific requirements for each type of document. 3. Finally, we will look at the specific issues that are likely to arise during your inspection visits and the sort of solutions that you will need to be able to offer.
- What is being made? Most of us when attempting a task need some sort of documentation.
- The drawing was wrong!
- Documentation is an essential part of QA and relates to all aspects of GMP. The pharmaceutical industry must have a good document framework (infrastructure). It is important for a manufacturer to get the documentation right in order to get the product right. There are a number of purposes for documents: They are used to define specifications for materials and for methods of manufacture and control. They ensure that everyone concerned with manufacture and QC knows what to do, how and when to do it. They allow decisions to be taken on batch release. They provide an audit trail, which is particularly important in the case of suspect batches.
- Documents should be designed, prepared, reviewed and distributed with care. In terms of design, there is no single right answer – the one thing you can be sure about is that every company will come up with a different design. However, it is better for the operators if a consistent approach is taken. It is possible for some of the documents to be combined, but generally they should be separate. They must comply with the relevant part of the manufacturing and marketing authorizations. All documents should be unambiguous with a title and a clear statement of purpose. They should contain clear, numbered references to each activity. They should have sufficient space to record relevant data. They should be easy to check and all relevant activities should be recorded on them.
- Instructions must be in the imperative – Go , Do, Stop, Mix, Blend, Wash, etc...... Look for short sentences. Long sentences do not allow the reader time to grasp messages. A florid, roseate style over endowed with polysyllabic phraseology confuses the reader.
- Documents should be designed, prepared, reviewed and dated by appropriate authorized persons. No document should be changed without authorization. Any alteration made to a document should be signed and dated; the alternation should permit the reading of the original information. Where appropriate the reason for the alternation should be recorded.
- Distribution of documents needs to be carefully controlled in order to ensure that the most up-to-date version is always being used. There should be a distribution list, if appropriate, attached to the document. Unauthorized photocopying of original documents should be actively discouraged. Some companies manage this by having part of the front page printed in colour, or by using an official stamp or other means of identification. There should be an SOP for distribution, retrieval and preparation of documentation. A document register is required. This ensures that change control over all documents is properly managed. Some documents may be stored electronically. Special controls have to be developed. If documentation is handled by electronic data-processing methods, only authorized persons should be able to enter or modify data in the computer, and there should be a record of changes and deletions; access should be restricted by passwords or other means, and the entry of critical data should be independently checked. Whichever way the master is stored, it is important that clear copies are reproduced for use with individual batches.
- This slide summarizes all the types of documents that are listed in the WHO GMP text, plus three additional ones. We will review each one in detail later in the session, but at this point, we will run through the list to make sure we are aware of all the requirements (Note for the trainer: that makes a good group session for audience participation rather than just reading the list to the seminar. One can also ask what must go on the e.g. Release label, or cleaning label, etc......) Labels are required for all containers, equipment and premises. Specifications and testing procedures are required for all starting materials, packaging materials, intermediates, bulk and finished products. There must be a master formulation for all manufacturing processes and a packaging instruction for each stock-keeping unit that is produced. Batch processing documents and records are required for all manufacturing processes. Batch packaging documents and records are required for packaging operations. Standard operating procedures (SOPs) are required for all operations that are not product-specific, whether related directly to manufacturing or to operation of the facility. The following are three examples of other documents that are useful and frequently found: Stock control records are usually used for all materials that are stored in the warehouse. Distribution records are usually used for all batches of material that are dispatched from the warehouse. A water quality manual describes all aspects of the water system design, operation, maintenance and water quality testing.
- There are two classes of labels. There are the finished product labels, which must meet national drug regulatory authority requirements as specified in the marketing authorization. Then there are the labels used within the factory to control processes. Labels are required for all containers of materials, whether for starting materials, intermediates or finished products; there must be sample labels and labels that are applied to materials that have been sampled; there must also be labels for all process equipment and for premises that are in use for manufacturing. The labels should be clear and unambiguous. Where possible, it is advisable for companies to use colours to indicate status (quarantine, accepted, rejected, cleaned or dirty). Companies generally have their own systems for internal labelling that define what information is carried, but for finished products, there is a national requirement. Responsibility for labelling varies with company practice, but the process is generally overseen and controlled by the QC department. QC staff are responsible for issuing status labelling when a material has been approved or rejected. The responsible production and/or QC staff should sign labels stating that equipment is clean and available for use. Reference standards (both primary and secondary) must be appropriately labelled and the issue of these must be controlled.
- There are two classes of labels. There are the finished product labels, which must meet national drug regulatory authority requirements as specified in the marketing authorization. Then there are the labels used within the factory to control processes. Labels are required for all containers of materials, whether for starting materials, intermediates or finished products; there must be sample labels and labels that are applied to materials that have been sampled; there must also be labels for all process equipment and for premises that are in use for manufacturing. The labels should be clear and unambiguous. Where possible, it is advisable for companies to use colours to indicate status (quarantine, accepted, rejected, cleaned or dirty). Companies generally have their own systems for internal labelling that define what information is carried, but for finished products, there is a national requirement. Responsibility for labelling varies with company practice, but the process is generally overseen and controlled by the QC department. QC staff are responsible for issuing status labelling when a material has been approved or rejected. The responsible production and/or QC staff should sign labels stating that equipment is clean and available for use. Reference standards (both primary and secondary) must be appropriately labelled and the issue of these must be controlled.
- There are two classes of labels. There are the finished product labels, which must meet national drug regulatory authority requirements as specified in the marketing authorization. Then there are the labels used within the factory to control processes. Labels are required for all containers of materials, whether for starting materials, intermediates or finished products; there must be sample labels and labels that are applied to materials that have been sampled; there must also be labels for all process equipment and for premises that are in use for manufacturing. The labels should be clear and unambiguous. Where possible, it is advisable for companies to use colours to indicate status (quarantine, accepted, rejected, cleaned or dirty). Companies generally have their own systems for internal labelling that define what information is carried, but for finished products, there is a national requirement. Responsibility for labelling varies with company practice, but the process is generally overseen and controlled by the QC department. QC staff are responsible for issuing status labelling when a material has been approved or rejected. The responsible production and/or QC staff should sign labels stating that equipment is clean and available for use. Reference standards (both primary and secondary) must be appropriately labelled and the issue of these must be controlled.
- Test procedures must be validated or verified for the available facilities before they are used for routine testing. Compendial methods need to be verified. This means that the method is demonstrated to give correct results in the laboratory facilities available. Specifications will include tests for identity, content purity and quality. Specifications should be dated and authorized. The responsibility for their issue and maintenance rests with the QC department. It may be necessary to update the documents occasionally in line with national compendiums or the company's requirements. Written specifications are required for all starting and packaging materials including water in all its various standards. The minimum requirements for these documents are: INN name and internal code reference Reference to pharmacopoeia monograph if appropriate Test parameters and acceptance criteria Other information may include: Details of supply, testing methodology and storage conditions. For packaging materials, there should be reference to compatibility with the drug. For all materials, the frequency of retest should be specified. If intermediates or bulk products are either purchased or dispatched, then they will need a specification. One will also be required if the data obtained from these materials are going to be used in the assessment of the finished product. They will be similar to the specification for the starting material or finished product, as appropriate. For finished products, the specification should include the following information: Name and internal code reference Name of the active ingredients The formula (or a reference to it) Description of dosage form and packaging Sampling and testing methodology Test parameters and acceptance criteria Storage conditions Shelf-life. Specifications and test procedures will be used by the QC department and are generally located in the laboratories.
- There must be a formally approved master formula for each product that is manufactured, in each batch size. The information that it should contain includes the following: Name of the product with product reference code Dosage form, strength and batch size A full list of materials including quantities and unique reference code for each Expected final yield with acceptable limits (plus intermediate yields) Processing location and principle equipment
- There must be a formally approved master formula for each product that is manufactured, in each batch size. The information that it should contain includes the following: Methodology for equipment preparation (cleaning, calibration, etc......) Stepwise processing instructions (space for operator to sign, check signature, recording of times, quantities, temperatures, etc......) Details of in-process controls with instructions for sampling and acceptance limits Storage requirements and any special precautions.
- The packaging instruction is the similar to the master formula, but covers packaging rather than manufacturing. There should be one document for each product and pack size. The information that it should contain includes: Name of the product Dosage form, strength and method of administration Pack size (number, weight or volume of product in finished pack) List of all packaging materials (quantities, size and code number). (Continued on next slide)
- The packaging instruction - continued: Examples of printed packaging materials, with location of batching information Special precautions, including area clearance checks Description of the packaging operation In-process control checks, with sampling instructions and acceptance criteria. Both these documents are used as references in the development of processing records. They should be located in development, quality control and production departments. The master formula is frequently used as the master batch-processing document. It is often photocopied to provide the individual batch-processing document. Whatever method is used, it must ensure that there can be no transcription error. The batch-processing document is never a hand-written copy. The same method can be used to prepare the batch packaging document.
- The packaging instruction - continued: Examples of printed packaging materials, with location of batching information Special precautions, including area clearance checks Description of the packaging operation In-process control checks, with sampling instructions and acceptance criteria. Both these documents are used as references in the development of processing records. They should be located in development, quality control and production departments. The master formula is frequently used as the master batch-processing document. It is often photocopied to provide the individual batch-processing document. Whatever method is used, it must ensure that there can be no transcription error. The batch-processing document is never a hand-written copy. The same method can be used to prepare the batch packaging document.
- A batch processing record (continued): The information required in the batch processing record includes: Reference number and quantity of materials used in the batch Main processing steps and key equipment In-process controls carried out, and the results obtained Yield at each stage with comments on deviations Expected final yield with acceptable limits Comments on any deviations from the process. Information that does not change, such as the product name, process steps and theoretical quantities of material, can be printed on the master copy. Variables, such as actual quantities of materials used and yields are entered by the operators during the manufacturing process.
- The batch packaging record is required for every batch or part batch that is packaged. It is developed from the relevant part of the packaging instructions and, once again, its review is an important part of the batch release process. Depending on company practice and the design of the document, it may be specific to a particular batch size or may be used for a variety of sizes. The information required for the completed batch packaging record, once again, consists of a combination of pre-printed material and data that are added by the operators during the process: Name of the product, batch number and quantity to be packed Batch number, theoretical quantity and actual quantity of finished product Reconciliation calculations Dates and times of operation Name of person responsible for packaging Initials of operators carrying out each step Checks made and results obtained
- The batch packaging record - continued: Details of packaging operation, including equipment and line used Returns to store Specimen of printed packaging materials, with batch coding Comments on deviations from the process and actions taken Reconciliation of packaging materials, including returns and destruction. If returns to the stores are permitted for printed packaging materials, they should first be checked to make sure that they have not been batch coded. A QC signature is required as part of this process, either on leaving the packing hall or on being received in the stores. If excess materials are destroyed, there must be a record of the quantities on the batch documentation. There should also be a procedure covering destruction, including methods and responsibilities. Reconciliation is of vital importance since it helps to confirm that the batch has been processed correctly. Any significant variation in materials should be taken as an indication that there could be a problem. Inspectors should check for investigation of these variations before the batch is signed off. Finally, area clearance checks should show no foreign materials are carried over from one operation to the next.
- Although useful reference documents for inspectors, Standard Operating Procedures (SOPs) are written for the benefit of the persons carrying out the operation in question. They should be written so that the user can easily understand them. If possible, they should be written by or with the operators, to ensure that they accurately reflect what happens in practice. They will be written by the department responsible for carrying them out, but should also be approved by the QA department, if appropriate. Master copies of procedures should be stored by the responsible department or centralized in the document control department. Authorized copies of each procedure should be stored adjacent to the place where the operation will be carried out, as a reference document that can be consulted at will. All critical equipment should have logbooks in which maintenance and cleaning are recorded. A record should also be kept of the use of this equipment. The procedures for sanitation should include methods, equipment, materials, responsibilities and the schedule for carrying them out.
- SOPs are required for a whole range of activities within the facility and may include the following: Receipt of all material deliveries Internal labelling, quarantine and storage of materials Operation, maintenance and cleaning of all instruments and equipment Sampling of materials Batch numbering systems Material testing at all stages of production
- SOPs are required for a whole range of activities - continued: Batch release or rejection. Maintenance of distribution records Equipment assembly and validation Calibration and operation of analytical apparatus Maintenance, cleaning and sanitation Personnel recruitment, training, clothing and hygiene Environmental monitoring Pest control Complaints Recalls Returned goods. Additionally, deviation and fault analysis and investigation procedures for out-of-specification results are very significant. For further details on SOP requirements, refer to the WHO GMP text.
- Finally, we turn to three types of documents that are not directly mentioned in the WHO GMP texts: stock control records, distribution records and water quality manuals. Although not specifically listed, the need for these documents is implied in the lists of requirements under QA, GMP and QC. The first two documents remind us that the need to record everything that a company does before the materials reach the production floor and continues after the finished product is sent to the warehouse. Stock control documentation is required for raw materials, packaging materials and finished products. The records include batch numbers, status, quantities and expiry date. They may be manual or electronic, but must take into account the status of the batch in question. They ensure an appropriate system of material rotation, such as FIFO (first in, first out) or EEFO (earliest to expire, first out). The records will be validated by the physical stock check carried out periodically in the warehouse. For distribution, there should be one record per batch of material. It should contain the batch number, quantity and destination of each delivery. This means that, in the case of a product recall, the information on distribution can be obtained rapidly from a single source. Using copy invoices as distribution records is not advisable unless the batch number is recorded. If a computer-controlled stock management system is used, this can provide a very acceptable method of recording distribution.
- The requirement for a water quality manual reflects the importance of purified water, in its various forms, to the pharmaceutical industry. The manual should contain full details of the design of the system, its operation and maintenance. It should also contain details of testing requirements. Microbiological and chemical quality has to be developed. The manual is a combination of information from suppliers' manuals and internal procedures.