Auditing in QA and Engineering department.pptx

This presentation contain basic information about auditing in QA and Engineering department. used to be as a guide material

1. Auditing in QA and Engineering Department Presented by: Nishi Ladhawala Enroll.no. 232280824002 M.Pharm QA Sem -2 Department of Pharmaceutical CHEMISTRY AND QUALITY ASSURANCE

2. Contents Introduction Points to be consider during audit Audit Process Auditing of Quality Assurance Department Objectives Audit Format and Approaches Checklist Auditing of Engineering Department Critical systems ( HVAC System, WFI, ETP) 2

3. Introduction A Pharmaceutical A udit is a systematic, independent examination of a Pharmaceutical company's operations and processes to ensure compliance with Good Manufacturing Practices (GMP), regulatory guidelines, and quality standards.   Audits can be conducted internally, by regulatory authorities, or by third-party organizations to verify that companies meet industry requirements for producing safe and effective medicines . Audit mainly divided into two categories: Internal Audit External audit 3

4. Internal Audit Internal Audit is carried out by a team of interdepartmental personnel at least twice a year to assess the compliance to quality management system and customer satisfaction. Also known as Self inspection or First party audit. External Audit Supplier and Customer Audit recognize as Second party audit . Other than supplier or customer called as Third party audit (Regulatory Audit). 4

5. Points to be consider during audit 1. Compliance (do we comply with the standard) Example: Desk audit of high level systems 2. System (the theory) Example: Audit of Document control 3. Process (the practice) Example: Audit of any process (manufacturing) 4. Product (the result) Example: Audit of finished products to fulfil technical specifications 5

6. Audit Process Prepare for the audit Perform the audit Report the results Perform corrective action 6

7. Guidelines for Audit The ISO, a global leader in the development of International standards, is instrumental in boosting interest in quality audits among manufacturers and other types of businesses when it published the ISO 9000 standards in 1987. Today, popular standards such as ISO 9001: 2000, ISO 14001:2004 all require internal audits of the quality system (or the environmental management system in the case of ISO 14001: 2004). Under these standards, audit serves as a mechanism for evaluating and improving quality. The same principle is reflected in a number of regulations enforced by the Food and Drug Administration. The current good manufacturing practice (CGMP) regulations for pharmaceuticals (21 CFR Parts 210-211) include general requirements for regular evaluation of quality standards. For example, the “Guidance for Industry Quality Systems Approach to Pharmaceutical CGMP Regulations” recommends internal audits and supplier audits 7

8. Auditing of QA Department A quality assurance audit is a documented, systematic process, performed in a planned manner by competent independent personnel with the objective of evaluating the application by an organization to the principles and requirements of defined quality regulations and customer expectations”. The word “Independent” here is very important and is use here in the sense that the reviewer (auditor) is neither the person responsible for the performance under review nor the immediate supervisor of that person. An independent audit pro vides an unbiased picture of performance. 8

9. Functions of Quality Assurance Development and Implementation of Quality Systems Compliance Monitoring and Auditing Batch Release and Product Review Validation and Qualification Change Control Management Training and Personnel Qualification Investigations and Corrective Actions 9

10. Objectives 1) An audit is a “ B enchmarking P rocess ”, i.e. an audit will give a status of the current performance of a process. This status can be measured against a published standard, or versus an approved operating procedure, versus a peer department, versus competitor companies, etc.. 2) The audit may identify shortcomings in process performance, may identify changing trends in performance, may identify deficiencies in staff knowledge or competence. Any such findings can then become the basis for improvement activities. 3) The quality audit should be a means of standardization . By implementing an audit program, equivalent standards of performance can be developed across different functions. The knowledge gained can be applied to ensure procedures are consistently utilized or equivalent competence requirements are set for staff. In the wider community, regulatory bodies for example use the quality assurance audit, to ensure quality standards are consistent across different product manufacturers. 10

11. Cont … 4) The quality assurance audit is frequently applied back through the supply chain, where purchasing organizations utilize audits to force minimum quality standards on suppliers. Frequently a supplier cannot become “approved to supply” a product or service, without first having passed the audit and addressed any shortcomings in their quality management system. 5) Learning and Training . A key point to understand as part of the audit program, is the potential for learning and knowledge transfer during the audit process. Where the auditor has a good understanding of the product or process, he / she can use the audit as a form of training for the person being audited. By explaining the reasons for particular requirements, or test points, or record requirements, the person being audited can personally develop their process or product knowledge. 6) Regulatory and standard compliance . The audit will confirm the compliance status of a process or product versus applicable regulatory or standard requirements. The audit can expose any gaps against requirements, which can then be addressed. 11

12. Cont … Quality assurance auditing is a concept widely used in internal, external and customer audits for measuring QA within the enterprise. The greater challenge is ensuring that procedures correctly mirror documented standards. Because a single document or research cycle for any mfg. product can result in abundance of documents and forms , companies establish QA departments to ensure process quality can be maintained. Its important to regularly audit the QA procedures so that the management can evaluate the efficiency of these procedures. A large amount of QA work involves in-process tests and on-line inspections that should be audited along with the specific departments. The goal of QA audit, then is to continually improve and ultimately build confidence in your product. 12

13. Audit Format and Approaches So, the basic premise is that “A quality product can only be produced and distributed by: Quality inputs Quality process Hence, Quality Assurance Audit should be checked for the quality of all inputs, processes and also confirm that the output i.e. the finished pharmaceutical product also meets the desired quality specifications and requirements of the ultimate customer or uses of the finished product.” Questioning Theory: It says; the auditors should ask questions about every “Input” and “Process” to satisfy himself about their quality e.g. (5W and 1H) How? , What? , When? , Where? , Who? , Why? 13

14. Ask as many questions as you think needed, without hesitation to see that the minimum quality of all inputs and processes is satisfactory met. The range of questions should cover following and many other areas as well e.g.; Personnel Buildings Equipment Systems Processes Quality control Manufacturing Validation Outsourcing Complaints and product returns 14

15. C ont … If the auditors ask questions and satisfied with the answers and proofs of their answers by documentations system or any other way , the audit should normally be called satisfactory. In short , the manufacturer does the activities to produce a quality finished product a quality finished product and the auditor verifies the manufacturer has actually done all those using appropriate inputs and hence the finished product produced by him can assure the quality of the product to the ultimate customer and sees that the customer is not only satisfied by delighted. 15

16. Checklist of QA Department 1.0 General checklist 1.1 Does the company have a later quality policy statement? 1.2 Does the company have an updated organization chart? 1.3 Are the previously audited records maintained? 1.4 Are production and control operations clearly specified in a written form and cGMP requirements are adopted? 1.5 Are responsibilities clearly specified in the job description? 1.6 Are all necessary controls on starting materials, intermediate products, and other in process controls, calibrations and validation carried out? 1.7 Are finished products correctly processed and checked according to the written products? 16

17. 2.0 Validation Related Audit Checklist 2.1 Is validation properly documented and includes Validation Master Plan, Cleaning Validation Mater Plan Validation Protocols (HVAC, Purified Water, WFI, Process Validation, Cleaning Validation, etc.) Validation Reports and Equipment Qualification (IQ, OQ, and PQ)? 2.2 Are validation studies conducted in accordance with predefined protocols (VMP) and validation planners? 2.3 Have production procedures been validation (Process Validation)? 2.4 Does the process control (In – Process Checks) address an issue to ensure the identity strength ,quality, and purity of the product? 2.5 Are all weighing and measuring performed by a specialized and qualified person and observes by a second person and duly signed by both of them on the record sheet? 2.6 Validat ion of New Master Formula: Are new master formulas or methods of preparation adopted and step taken to demonstrate their suitability for routine processing , process-defined materials and equipment specified? 17

18. 2.7 Validation of Equipment and Materials: Are significant amendments to the manufacturing process, including any change in equipment and materials affecting product quality or re-productivity of process validated? Are validation records properly maintained and updated? 3 .0 Labeling 3 .1 Are labels to the containers, equipment or premises applied un-ambiguously according to the company’s agreed format? 3.2 Are labels of different colors indicating the status such as “Quarantined”, “Accepted”, “Rejected”, or “Cleaned” used? 3.3 Are all finished products labeled as per specifications? 18

19. 4 .0 Documentation and Records 4 .1 Are documentation meticulously maintained as per rules and regularly reviewed and kept up to date? 4.2 Is documentation maintained in properly segregated areas and easily available? 4 .3 Is a master list of documentation maintained? 4 .4 Is documentation accurate, clear & neat? Does it define specifications and procedures for all materials & methods of manufacture & control? 4.5 Are all the specifications, testing, procedures, master formulae, packing instructions, and standard operating procedures (SOPs) available, current & being followed? 4.6 Do the records provide the existence of documented evidence, traceability, and an audit trail that will permit investigation? 4.7 Does the record provide batch processing & packaging details including receiving the sample, processing equipment, analytical testing, and laboratory instrument records? 19

20. 5.0 Process Documents and Records Ensure the following documents/records are available at the time of Audit: 5.1Are all master copies of documents available? 5.2Specifications for intermediate and bulk products 5.3Batch processing records, Record for process operation. 5.5Batch packaging records, Record for packaging operation 5.7Record of Batch numbers, Analytical records of the batch. 5.9Record for finished product release procedures. 20

21. 6.0 SOPs Related Audit Check List 6.1 Are SOPs and associated records of actions, and conclusions reached available for the following at the premises? 6.2 Equipment Assembly and Validation. 6.3 Analytical apparatus and calibration 6.4 Maintenance, cleaning, and sanitization, 6.5 Personnel matters including qualification, training, clothing, and hygiene 6.6 Environmental monitoring. 6.7 Pest Control 6.8 Complaints 6.9 Drug recalls 7.0 Vendor Qualifications 7.1 Do you have an updated list of approved vendors? 7.2 Are the vendors supplying raw material (both active & inactive ingredients), primary packaging & printed components audited & found to be satisfactory? 21

22. 8.0 Change Control Program 8.1 Is there a format change control program in place supported by an SOP to initiate, review & approve changes in material, sources, processes, product packaging, equipment, batch size changes, etc. is it properly followed? 9.0 Sample 9.1 Does the company retain a sample of a lot or branch of the packaged / labeled drug for a period of at least 1 year after the expiration date on the label of the drug? 9.2 Does the company retain a sample of each lot batch of raw material? 9.3 Does the retained samples properly labeled and records maintaine d as per SOP? 22

23. 10.0 Stability Studies 10.1 Does the company have a prospective and concurrent stability studies program based on SOP and utilizing proper equipment i.e. climatic chambers maintained at 30 .C/65%RH for ambient and 40.C/75%RH for stress conditions and continuously monitored for temperature & RH. 10.2 Is the stability of finished products evaluat ed and documented prior to marketing? 10.3 Does the stability d ata support the self life assigned to the product? 10.4 Are any deviations in data reviewed and appropriate steps taken in c ase of stability issues? 11.0 Drug Recalls 11.1 Do you have an SOP for drug recalls? 11. 2 If answered yes to the above did you have any drug recall in the past 2 years? 23

24. 1 2.0 Annual Product Review 12.1 Is there a process in place to review statistical data (i.e. trend analysis, reworks, rejects, customer complaints) of all the products manufactured during the year? 12.2 Provide the name of the products manufactured by you along with the price list. 12.3 Provide the source of raw material for individual products. 12.4 Do you export your products if so then to whom and mention the name of the products? 13.0 Equipment's Logbooks 13.1 Are logbooks for major and critical equipment identified by the company kept? 13.2 Are the issuance of logbooks and archival properly documented? 24

25. Auditing of Engineering Department Any operation that is performed by the engineering department must be covered by written procedure. Calibration records should be relatively easy to audit. First, for each type of instrument, there should be a procedure detailing how the calibration is to be performed , what standard equipment is to used, and what deviation is permitted. There should also be recommended corrective action to be taken if deviation is exceeded. Examine several calibration forms and compare the recorded data with the requirement of SOP. Preventive maintenance records should be reviewed together with breakdown records. 25

26. A good Engineering Audit helps in Determining whether management of the main aspects of engineering (e.g., spare parts, change parts, personnel, work method, safety tools, time and cost analysis of maintenance, etc )is adequate. Analysis of down time will help in production. Scheduling department to make production schedules more reliable. 26

27. Critical Systems It includes, HVAC (Heating, Ventilation and Air conditioning) WFI (Water for Injection) ETP (Effluent treatment Plant) HVAC System: It is integral component of pharmaceutical facility functionality. The system is needed for maintenance of a suitable temperature, for continuous flow of air, which ultimately prevent cross contamination and accumulation of air and to ensure the cooling of air in the premises. 27

28. HVAC consists of: AHUs (Air Handling Units) Dehumidifier/Heater Filters (Pre & HEPA ) Dust extractors Ducting (For delivery of controlled air) Supply Fans Dampers Humidity temperature/pressure sensors Mixer Heating /cooling coils 28

29. Auditing of HVAC systems consist of following questions:- Have you carried out Air flow patterns for laminar air flow, air stations, pressure gradients studies, etc.? Have you studied filter integrity tests (Filter leakage test)? Have you checked and recorded air flow velocity and air changes per hour? Have you checked and recorded particle counts? Have you evaluated sterile manufacturing area for microbial loads in area and surfaces in the aseptic room Have you tested and recorded pressure differential in various rooms? Have you studied and recorded temperature and humidity recovery in rooms? Have you done temperature and humidity mapping in the rooms and recorded? 29

30. Water and Water for Injection System: Types of Water Portable Water Purified Water WFI Sterile Water for Injection Sterile Water for Bacteriostatic injection 30

31. The auditors when auditing pharmaceutical water system: They physically observe the water treatment plants in operating conditions. They will certainly check the documentation systems for water systems. They ask some questions to verify and compliance needed for the water processing storage and use. List of questions include: Does the water treatment plant suitable for your needs (e.g., from capability and capacity point of view)? Is that equipment operated and maintained satisfactory to meet your requirements? Do you have satisfactory document evidence? Are water sources, water treatment plants and treated water checked for contamination and maintained regularly for chemical and microbial quality? Are pressure relief outlets of water storage systems protected by microbial air filters? Is the water processed stored and distributed in such a way to discourage microbial growth? 31

32. Does your water system monitoring cover: Sample size and method of sample collection? Are sample locations identified and marketed suitably? Is the frequency of sampling clearly stated? Do tests meet the minimum pharmacopeial standards? Are records of the results of the monitoring and any of the recommendation taken are maintained? What type of water treatment systems you have? How purified, distilled, water for injection stored? How do you store and protect produced water from contamination particularly microbial contamination? Do you have U.V. light installed in purified distribution system? Is your water sampling procedure cover the following critical points? Location of sampling, Size of sampling, Frequency of sampling, Tests and specifications including; chemical, microbiological and pyrogen tests. 32

33. Water for injection Some key guidelines related to W.F.I. are as follows: Pharmaceutical water production, storage and distribution systems should be designed, installed and commissioned, validated and maintained to ensure the reliable production of water of appropriate quality. The capacity of the system should match the intended use. Water should be produced, stored and distributed in a manner that prevents unacceptable microbial, chemical or physical contamination. Source water should be regularly monitored for its chemical, microbiological quality. Records of the monitoring results, trend analysis and any actions taken should be maintained. W.F.I Specifications: W.F.I should be prepared form drinking water usually with a further treatment as a minimum quality feed water. W.F.I. is not sterile and is not a final dosage form. It is an intermediate bulk product. W.F.I. is the highest quality of pharmacopeial water for pharmaceutical use. 33

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35. Key Audit Points for WFI Systems: Check sampling and monitoring plan with a drawing of all sample points. Check the setting of monitoring, alert and action levels. Check monitoring results and evaluation of trends. Inspect the last annual system review. Review the changes made to the system since the last audit and check that the change control has been implemented. Review the deviations recorded and their investigations. Carry out a general inspection of the system for status and condition of the system. Review the maintenance, failure and repair logs. Check calibration and standardization of critical instruments. 35

36. Effluent Treatment Plant ETP audit determine if contractor complied with ETP contract, regulations and policies. Information shown here summarize routine ETP audit processes. Auditors will provide detailed information and guidance through an actual audit. Importance of ETP: To remove as much of the solid and organic matter as possible Reused for various hospitals purpose To provide some degree of treatment of the waste water before it can be used for other purpose. Effluent: Liquid waste flowing out of a factory, farm, commercial establishment or household into a water body such as river, lake. 36

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38. Key points for ETP audit: Evaluate the personal protective equipment’s used to verify these are appropriate and sufficient. Physical examination of the ETP is carried out to see each level is appropriately maintained and operated. The samples are taken for analysis if needed. The reports of the organizations test are verified against the sort requirements particularly with reference is COD, BOD, pH, etc. The auditor must get himself satisfied with the human health issue involved. The auditor should look for the overall, civil, mechanical and electrical maintenance of the ETP to see that the ETP is well maintained and suitability operated to get the desired outcome from the ETP processing. Relevant SOP’s and evaluation reports must be verified to see the compliance. Final chemical and biochemical reports must be verified to see that the results are within the specified limits. The auditor should evaluate the organization management’s commitment’s human health environmental conditions, through their efforts for ETP. 38

39. Common issues often defeated in engineering audit: Unsuitable organization structure of department (e.g., excess or lack of staff) Training deficit (lack of staff training) Bad structuring (especially no staff present at key moments). Shortage of spares. Lack of inventory or over inventory. Lack of key tools. Inadequate preventive maintenance plans. Lack of awareness on the use of personnel protective equipment. 39

40. Reference J.P. Russell, The Quality Audit Handbook: Principles , Implementation and Uses. 2 nd Edition. ASQ Quality Press : Milwaukee ,Wisconsin. Shayne Cox Gad , Pharmaceutical Manufacturing Handbook : Regulations and Quality. A John Wiley & Sons, Inc., Publication, Cary, North Carolina. Donald .C . Singer, Raluca . Lloana . Stefan, Jacobus F . Van Staden , Laboratory Auditing For Quality and Regulatory Compliance: Drugs and the pharmaceutical sciences. James Swarbrick PharmaceuTech , Pinehurst, North Carolina. Pharmaceutical dosage forms: Parenteral medication, Revised and Expanded, Edited by Kenneth E. Avis, Herbart A. Liebermann and Leon Lachman, volume 3, Second Edition, page no:- 363-420. Quality manual, D.H.Shah, First edition, page no:- 184-216. https://pharmaguddu.com/audit-check-list-for-quality-assurance-pharmaceuticals/ 40

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