GMP & Quality Assurance. Mayur Sushir Dept of Microbiology MJC

Transcription

1 GMP & Quality Assurance Mayur Sushir Dept of Microbiology MJC

2 Introduction GMP ensures that quality is built into the organization & processes involved in manufacture GMP covers all aspects of manufacture including collection, transportation, processing, storage, QC & delivery of the finished product

3 GMP Part of QA which ensures that products are consistently produced & controlled to the quality standards appropriate to their use. GMP is an integral part of QA.

4 QA, GMP & QC inter-relationship QA It is the sum total of the organized arrangements with the objective of ensuring that products will be of the quality required for their intended use

5 QA, GMP & QC inter-relationship GMP Is that part of QA aimed at ensuring that products are consistently manufactured to a quality appropriate to their intended use

6 QA, GMP & QC inter-relationship QC Part of GMP concerned with sampling, specification & testing, documentation & release procedures which ensure that the necessary & relevant tests are performed & the product is released for use only after ascertaining it s quality

7 QC & QA Part of GMP which is concerned with sampling, specifications, testing and with in the organization, documentation and release procedures which ensure that the necessary & relevant tests are carried out QA is the sum total of organized arrangements made with the object of ensuring that product will be of the Quality required by their intended use.

8 QC & QA Operational laboratory techniques & activities used to fulfill the requirement of Quality All those planned or systematic actions necessary to provide adequate confidence that a product will satisfy the requirements for quality

9 QC & QA QC is laboratory based QA is company based

10 GMP GMP in solid dosage forms GMP in semisolid dosage forms GMP in Liquid orals GMP in Parenterals Production GMP in Ayurvedic medicines GMP in Biotechnological products GMP in Nutraceuticals & cosmeceuticals GMP in Homeopathic medicines

11 GMP Good Manufacturing Practice Good Management Practice Get More Profit Give more Production GMP Training with out tears

12 Ten Principles of GMP 1. Design & construct the facilities & equipments properly 2. Follow written procedures & Instructions 3. Document work 4. Validate work 5. Monitor facilities & equipment 6. Write step by step operating procedures & work on instructions 7. Design, develop & demonstrate job competence 8. Protect against contamination 9. Control components & product related processes 10. Conduct planned & periodic audits

13 Beyond GMP Reduce pollution - Zero discharge Adaptation of environment friendly methods Consideration for better & healthier life tomorrow Consideration of ethics in life One should begin with end in mind otherwise it will be the beginning of the end

14 Cost of effective GMP In fact Cost benefits positive cost benefits of GMP/QA Good plant lay out, Smooth work flows, Efficient documentation systems, well controlled process, good stores lay outs and stores records- These are Good manufacturing practices Reduction in work in process & inventory holding costs Avoidance of cost of Quality failure ( cost of waste, of rework, of recall, of consumer compensation and of loss of company reputation)

15 List of important documents in GMP Policies SOP Specifications MFR (Master Formula Record) BMR Manuals Master plans/ files Validation protocols Forms & Formats Records

16 How do GMPs of different countries compare? At a high level, GMPs of various nations are very similar; most require things like: Equipment & facilities being properly designed, maintained, & cleaned SOPs be written & approved An independent Quality unit (like QC and/or QA) Well trained personnel & management

17 Basic Requirements of GMP All manufacturing processes are clearly defined, systematically reviewed, & shown to be capable of consistently manufacturing medicinal products of the required quality & complying with specifications. Critical steps of the process and significant changes to the process are validated

18 Why GMP is important A poor quality medicine may contain toxic substances that have been unintentionally added. A medicine that contains little or none of the claimed ingredient will not have the intended therapeutic effect.

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20 QUALITY RELATIONSHIP Quality Management Quality Assurance G.M.P. QA GMP QC Quality Control

21 What is Quality Management? The aspect of management function that determines & implements the quality policy The overall intention & direction regarding quality, as formally expressed & authorized by top management

22 BASIC PRINCIPLE OF QUALITY MANAGEMENT (1) Manufacturer should ensure the cosmetic products comply with the requirements of ASEAN Cosmetic Directives (ACD). They should also comply with any other applicable regulations pertaining to your specific country. The attainment of this quality objective should be led by the senior management & requires the participation and commitment by staff, by the company s suppliers and distributors.

23 BASIC PRINCIPLE OF QUALITY MANAGEMENT (2) To achieve the reliable quality objective, there should be a comprehensive QA system incorporating GMP. The QA system should be fully documented & its effectiveness should be monitored.

24 QUALITY ASSURANCE QA covers all matters which individually or collectively influence the quality of a product. All parts of QA system should be adequately resourced with: Competent personnel Suitable & sufficient premises, equipment & facilities

25 Principles of Quality Assurance (QA) 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 QA incorporates GMP and also product design & development which is outside the scope of this module

26 BASIC REQUIREMENTS OF QA Ensure that products are designed and developed based on sound scientific rationale and with GMP or GLP principles being taken into consideration. Ensure that managerial responsibilities are clearly specified. Ensure that production and control operations are clearly specified and GMP is adopted. Organize supply & use of correct starting & packaging materials. Ensure that finished products are correctly processed & checked before release. Ensure that products are released after review by authorized person. Provide satisfactory arrangement to ensure products are stored, distributed & handled appropriately. Put in place a mechanism for regular self inspection / internal quality audit.

27 GOOD MANUFACURING PRACTICES Part of QA which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use. Minimize risks : cross contamination mix up Ensure products/materials are traceable to the original source. Product testing is not reliable way to assure product quality. Should BUILD quality into the product! Production and quality control functions should be independent of each other. All manufacturing process are clearly defined and systematically reviewed.

28 All necessary facilities/resources for GMP should be provided : adequate, qualified and well-trained personnel suitable premises and sufficient space suitable location good personal hygiene and proper sanitation suitable equipment and services

29 QUALITY CONTROL QC is part of GMP. QC is concerned with sampling, specification and testing. Manufacturer should have a QC department. QC should be headed by an appropriately qualified and experienced person. QC should be independent from production and other departments. Ensure that the necessary and relevant tests are actually carried out. Ensure that no materials or products will be released for sale or supply, until their quality have been evaluated and judged to be satisfactory.

30 SCOPE OF QC Items concerned : Starting materials Packaging materials Bulk products Intermediate and finished products Environmental conditions

31 BASIC REQUIREMENTS OF QUALITY CONTROL (1) Adequate facilities, trained personnel and approved procedures should be available for sampling, inspecting and testing and, where appropriate, environment monitoring. Sampling by QC personnel & testing by approved methods. Approved test methods. Maintenance of QC records & failure investigation records.

32 BASIC REQUIREMENTS OF QUALITY CONTROL (2) Ingredients comply with regulatory specification (grade, composition, strength) Review and evaluation of production documentation Assessment of process deviations Release of batches by authorised person Sufficient reference samples of starting materials and finished products

33 OTHER DUTIES OF QC Establish QC procedures Manage reference standards Ensure correct labeling Stability testing (if applicable) Complaint investigation Environmental monitoring

34 QUALITY CONTROL ACTIVITIES QC should cover the following: a. Sampling b. Specification c. Testing d. Release procedures e. Recalls and complaints f. Decision making in all quality matters g. Definition of product quality h. Laboratory operations i. Release authorisation j. Investigation and reporting

35 BASIC REQUIREMENTS OF QUALITY CONTROL Adequate facilities, trained personnel and approved procedures should be available for sampling, inspecting and testing and, where appropriate, environment monitoring. Sampling by QC personnel & testing by approved methods. Approved test methods. Maintenance of QC records & failure investigation records. Ingredients comply with regulatory specification (grade, composition, strength) Review and evaluation of production documentation Assessment of process deviations Release of batches by authorised person Sufficient reference samples of starting materials and finished products

36 OTHER DUTIES OF QC Establish QC procedures Manage reference standards Ensure correct labeling Stability testing (if applicable) Complaint investigation Environmental monitoring

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38 PERSONNEL Adequate staff with relevant knowledge, experience and capabilities in assigned task a. Production and QC are headed by different persons, neither of whom shall be responsible to the other b. Responsibilities and authority of key personnel are clearly defined c. Training on the understanding of procedures, work instruction, GMP principles, etc.

39 Personnel Qualifications Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions. Training shall be...

40 There are competent and appropriately qualified personnel in sufficient numbers to ensure service provision. The responsibilities of all staff should be clearly understood and recorded. All personnel receive initial and continuing training relevant to their needs. Only staff who have appropriate training are authorised to carry out that procedure. Training should be structured and continuous. Training records based on SOPs are a good means of evidencing that staff are able to perform tasks. Competency Assessments can also be used to assess procedural training.

41 3 Key Personnel The head of production The head of QC The head of QM (QA)

42 The head of production The head of production should be a qualified pharmacist, adequately trained, possess good practical experience in pharmaceutical manufacture & managerial skill. The head of production should have full authority & responsibility to manage production of pharmaceutical products.

43 The head of QC The head of QC should be a qualified pharmacist, have adequate training & practical experiences which enable him/her to perform him/her function personally. The head of QC should given full authority & responsibility in all QC duties.

44 The head of QM (QA) The head of QM (QA) should be a qualified pharmacist, have adequate training & practical experiences which enable him/her to perform him/her function personally. The head of QM (QA) should given full authority & responsibility in all quality system/assurance duties.

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46 PREMISES Specify the requirements of location, design, constructions and maintenance of manufacturing premises with respect to the following: a. prevention of contamination from surrounding environment and pests b. prevention of mix up of materials and products c. facilities such as toilet, changing rooms, sampling areas and QC lab d. defined areas for certain activities e. wall, ceiling, drains, air intake and exhaust, lighting and ventilation, pipe work and light fitting f. storage areas

47 Suitable location, design, constructions and maintenance for manufacturing premises : defined areas for certain activities (e.g material sampling & dispensing) wall, ceiling, drains, air intake and exhaust, lighting and ventilation, pipe work and light fitting storage areas of adequate space Physical separation of toilets and QC lab from production

48 Building & facilities 1. Design and construction features. 2. Lighting. 3. Ventilation, air filtration, air heating and cooling. 4. Plumbing. 5. Sewage and refuse. 6. Washing and toilet facilities. 7. Sanitation. 8. Maintenance.

49 Paint Finish Not only building paintwork must be considered but also equipment

50 Building Finishes: In module 1 we discussed the need for all facility components to complement each other. Therefore a good air handling system must be complemented by a building of good design and good finishes. On the next slide we will be looking at some of the Acceptable and Un-acceptable building finishes.

51 Building Finishes Not Acceptable Acceptable PVA Paint L Epoxy or Enamel paint J Window sills L Flush glazed windows J Exposed pipes L Smooth surfaces J Horizontal pipes & services L Concealed services J Open floor drains L Hygienic drains J Floor cracks, flaking floor surfaces L Homogonous sealed floors epoxy finish or welded vinyl J Ceiling cracks & joints L Smooth sealed ceilings J Exposed, open light fittings L Flush light fittings J Wooden furniture L S/Steel or Melamine furniture J

52 Floors / drains

53 Design and Construction Features Any building or buildings used in the manufacture, processing, packing, or holding of a drug product shall be of suitable size, construction, and location to facilitate cleaning, maintenance, and proper operation.

54 Product Areas Premises should preferably be laid out in such a way as: To allow the production to take place in areas connected in a logical order corresponding to the sequence of the operations, the requisite cleanliness levels, To avoid crowding and disorder, To allow effective communication and supervision.

55 Weighing Area The weighing of starting materials and the estimation of yield by weighing should be carried out in separate weighing areas specially designed for that use. Such areas may be part of either storage or production areas.

56 Storage Areas Specify the requirements concerning storage of materials/ products with respect to the following a. Space, design, security and cleanliness b. Storage of quarantine stocks c. Storage of hazardous substances d. Conditions of storage area e. (e.g. temperature & relative humidity) f. Receiving of incoming materials g. Stock control (e.g. FIFO principle, h. proper labeling on the container)

57 Ventilation, Air Filtration, Air Heating and Cooling Equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature shall be provided when appropriate for the manufacture, processing, packing, or holding of a drug product. Air-handling systems for... penicillin shall be completely separate from those for other drug products for human use.

58 Poor & Good Windows

59 QC Areas QC laboratories should be designed to suit the operations to be carried out in them. QC laboratories should be separated from production areas. Areas where biological or radioisotope test methods are employed should be separated from each other.

60 Ancillary Areas Rest and refreshment rooms should be separated from production & QC laboratory areas. Facilities for changing clothes and for washing and toilet purposes should be easily accessible & appropriate for the number of users.

61 Thank you for Your Kind Attention