Transcript Document
Quality Assurance System Objective- Definition : ‘Quality Assurance’ is the activity to provide the sufficient degree of confidence to all concern, to establish that the quality function is being performed adequately. Quality Assurance covers all matters which individually or collectively influence product quality. It is the sum total of well organized activities with an objective to ensure product quality. Quality Assurance incorporates cGMP and product designed and development Scope : Introduction- basic requirements, types & role of QA, Line clearance. Quality Assurance System Role of QA 1.Development QA/ CQA 2.R&D-QA 3.Engineering QA 4.IPQA Quality Assurance System Role of IPQA 1.In process checks 2.GMP 3.Line clearance 4.Documentation and controls 5.Training & development 6.ATR 7. Self inspection Quality Assurance System Principles of Quality Assurance Wide-ranging concept- covers all matters that individually or collectively influence the quality of a product Totality of the arrangements- to ensure that the drug is of the right quality for the intended use Quality Assurance incorporates GMP and also product design and development which is outside the scope of this module. Present Control of systems/QSIT Quality Policy and SOP manual Documentation of management review activities CAPA system Record keeping and Retrieval PAPC Quality Assurance System Requirements from QA Systems 1.Ensure products are developed correctly 2.Identify managerial responsibilities 3.Provide SOPs for production and control 4.organize supply and use of correct starting materials 5.Define controls for all stages of manufacture and packaging 6.Ensure finished product correctly processed and checked before release 7.Ensure products are released after review by authorized person. 8.Provide storage and distribution 9. Organize self –inspection & monitor compliance of Gap findings Line Clearance System Line Clearance: is a process which provide a high degree of confidence that the said line is free from any unwanted residue or left over of previous processing’s before proceeding for next process. Objective is to avoid cross contamination or mix up in the production, which may lids to serious issues such as complaints and product failure which affects quality of the product and indirectly status of the company. Following of the questions arises regarding this issues, 1.Does line clearance is mandatory? 2.Is it have any separate guidelines w.r.t.any regulatory authority? 3.Does line clearance require any written procedure for this? If yes then what are the criteria of checks? – area wise checklist? 4.Who is authorized to check ? 5.Why there should be third person check for the line clearance? 6. What are the importance of line clearance? Line Clearance System Regulatory Guideline : USFDA- PART 211 1.In USFDA-Part 211- Current good manufacturing practice for finished pharmaceuticals point No.:211.130 Packaging and labeling operations: There shall be written procedure designed to assure that correct labels, labeling, and packaging materials are used for drug products;such written procedures shall be followed. These procedure shall incorporate the following features: a) Identification and handling of filled drug product containers that are set aside and held in unlabeled condition for future labeling operation to preclude mislabeling of individual containers, lots, or portions of lots. Identification need not be applied to each individual container but shall be sufficient to determine name, strength, quantity of contents, and lot ar control number of each container. Line Clearance System b)Prevention of mix-ups and cross-contamination by physical or spatial separation from operations on other drug products. c)Identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch. d)Examination of packaging and labeling materials for suitability and correctness before packaging operations and documentation of such examination in the batch production record. e)Inspection of the packaging and labeling facilities immediately before use to assure that all drug products have been removed from previous operations. Inspection shall also be made to assure that packaging and labeling materials not suitable for subsequent operations have been removed. Results of inspection shall be documented in the batch production records. Line Clearance System Schedule M: 8.2. Precautions against mix-up and cross contamination8.2.3.To prevent mix ups during production stages, material under-process shall be conspicuously labeled to demonstrate their status. All equipment used for production shall be labeled with their current status. 8.2.4.Packaging lines shall be independent and adequately segregated. It shall be ensured that all left over of the previous packaging operations, including labels, cartons & caps are cleared before the closing hour. 8.2.5.Before packaging operations are begun, steps shall be taken to ensure that the work area, packaging lines, printing machines, and other equipment are clean and free from any products, materials and spillages. The line clearance shall be performed according to an appropriate checklist & records. 8.2.6.The correct details of any printing (for example of batch numbers or expiry dates) done separately or in the course of the packaging shall be re-checked at the regular intervals. All printing and overprinting shall be authorized in writing. 8.2.7.The manufacturing environment shall be maintained at the required levels of temperature, humidity and cleanliness. 8.2.8. Authorized persons shall ensure change-over into specific uniforms before undertaking any manufacturing operations, including packaging. Line Clearance System Regulatory Guidelines-EU and PIC Guidelines-Chapter 5: Production Processing operations : Intermediate and bulk products5.35 Before any processing operation is started, steps should be taken to ensure that the work area and equipment are clean and free from any starting materials,products, product residues or documents not required for the current operation. Packaging operations 5.44 When setting up a programme for the packaging operations, particular attention should be given to minimizing the risk of cross contamination, mix-ups or substitutions. Different products should not be packaged in close proximity unless there is physical segregation. 5.45 Before packaging operations are begun, steps should be taken to ensure that the work area, packaging lines, printing machines and other equipment are clean and free from any products, materials or documents previously used, if these are not required for the current operation. The line clearance should be performed according to an appropriate checklist. Line Clearance System Regulatory Guidelines-MCC Chapter 5: Manufacturing 5.4. Manufacturing Operations : 5.4.2.All manufacturing areas and equipment should be checked for cleanliness prior to starting production. 5.6 Contamination 5.6.7 Before any processing operation is stated, steps should be taken to ensure that the work area and equipment are clean and free from any starting materials, products,product residues or documents not required for the current operation. Chapter 5: Packaging 5.4. Packaging Operations : 6.3.2 Before packaging operations are begun, steps should be taken to ensure that the work area, packaging lines, printing machines and other equipment are clean and free from any products, materials or documents previously used, if these are not required for the current operation. The line clearance should be performed according to an appropriate check list and signed for. Certain checks e.g. printed packaging material, printing operations and bulk identity should be performed & signed for by a pharmacist or legally authorized person. Line Clearance System 1. 2. 3. 4. Line clearance – Standard Procedure Hence as per all above guidelines it is necessary to have a written procedure called as SOP for Line Clearance. SOP should cover all parameters such as responsibility, procedure, type of changeovers and area wise checklist to ease the process. It is required to have practice of line clearance in all the processing area, which can be divided into three parts, a.Dispensing Area. b.Manufacturing Area c.Packing Area. In all this three areas change over can be identified in two types, a.Minor b.Critical A minor change over is a change over between, 1. Batches of same product. 2. Batches of same product and same strength. 3. Batches of ascending strength of same product. Line Clearance System Line clearance – Standard Procedure 5.As minor change over will not cause any serious contamination the line clearance can be given by responsible person of the said department after checking all the points as per checklist. 6.A Critical change over can be identified as change over between, 1.Batches of different product 2.Batches of descending strength of same product. 3.Batches of descending / ascending strength with different color. 7.A contamination caused by such critical change over can be more serious effect on the product. So that clearance during such changeovers can be given by concerned person ( production officer) as a primary check, which must be again verified by (re inspected by) authorized person(QA person)as a secondary check. Line Clearance System Reasons for failure of line clearance 1.Inadequate ProcedureIt is important to have a very clear & adequate written procedure for line clearance. Procedure should understandable to the person who follows it. Hard to clean areas, where product may be remain after cleaning should be identified and clearly mentioned in the SOP. 2. Personnel80% failure of line clearance is due to personnel negligence and illiteracy regarding the subject. For this, persons should be trained properly to do their assign job.They should know the importance of subject and also why, when, what and how to clean the area. 3. Each area should have a picture/ outline sketch to describe the types of problem & effective way of doing the line clearance. 4.During on job training, demonstrate the line clearance activity practically which will be easy to understand for the packers. Line Clearance System 5. Area Specific detailed checklists should be in place considering the nature of problems, significance and impact. 6.Periodic meetings should be conducted to share with other colleagues ‘ The system –failure experiences/failure incident along with CAPA taken-to avoid repeat incidences in remaining areas’. 7.For repeated problems, review the situation and resolve the problem with cross functional dept. e.g. use removable panels.