The document provides details on conducting quality audits, including: 1) An overview of audit preparation such as developing an audit plan, selecting auditors, and preparing the auditees. 2) Guidelines for performing the audit such as conducting an opening meeting, touring the site, questioning techniques, and daily wrap-ups. 3) Details on audit report out including classifying observations as critical, major, or minor and conducting a close-out meeting.

1. The Quality Auditing [Training for Quality Auditors]

2. Course Syllabus and Agenda The Background and Basics Auditor Conduct and Necessary Skills Audit Preparation and Planning Performing the Audit Audit Report and Follow-up

3. AUDITING The Background and Basics

4. Definition: A quality audit is a systematic, independent and documented process of examining any activity of an organization based on objective evidence, to determine a. The extent to which quality activities and related results comply with the planned arrangements b. The extent to which these arrangements have been implemented effectively, and c. whether these arrangements are suitable to achieve the quality objectives. What is an Audit?

5. An independent and systematic examination to establish whether quality activities and related results comply with planned arrangements. A quality audit needs to look at effective implementation of quality arrangements and whether they are suitable for the achievement of objectives. It is an integral part of working toward a quality standard. What is an Audit? Continued…

6. Compliance audit: The process of checking whether the organization has implemented what they have stated and whether the people are doing, the documents had asked them to do. What is an Audit? Continued…

7. First party audit or self-audit or internal audit: Carried out by people of the organization or on behalf of the organization itself to examine its own quality system. Second party audit or audit by customer or external audit: Carried out by the customer on the organization or by organization on the suppliers to examine the quality of suppliers. Third party audit or independent agency audit or external audit: Carried out by an external independent agency to assess compliance usually for the purpose of certification. (For example: USFDA,MHRA,WHO GMP,ISO etc.) Types of Audits

8. Internal audit: Internal audit acts as the organizations eyes and ears to gather feedback for correction and improvement. The purpose of internal audit is to identify possible product/process improvements. to identify deficiencies in products or in the plant/quality management system. Internal Audit

9. Normally an audit should have positive approach with the objective of “ finding facts rather than faults ”. However in case of internal audit by the organization where the primary goal is “ correction and improvement ” the more faults found the more the corrections and greater the compliance. These audits must be conducted regularly in accordance with the audit plan. Normally audits must be carried out as per plan and schedules prepared each time for the audit. Internal Audit Continued…

10. AUDITOR Conduct and Necessary Skills

11. First, the auditor must have a certain amount of exposure to cGMPs. Second, the auditor must have some understanding of the manufacturing, QA, and QC environments and requirements. Third, the candidate must want to become a cGMP auditor, A “Draftee” generally does not perform too well. A Good Auditor should have..

12. Good oral and written communication skills Fact finding Unbiased Honest Tactful Attentive Patient Polite and Professional Traits of a Good GMP Auditor

13. A VERY Important Trait Common Sense !

14. Undesirable Traits of a GMP Auditor Poor Communications skills Arrogant Negligent Biased Vague Blaming Impatient Impolite

15. Dress in business clothing, appropriate to the climate and the business principles of your auditee. Be punctual. The auditee is also a very busy person, and his/her time is equally as valuable as yours. Be courteous, considerate and respectful – good manners cost nothing and will promote an open, honest environment. Be professional – you represent your department and Company. Do not be rude or too aggressive – the auditee, in a defensive move, will disengage from the audit and verbally shut down. Auditors Behavior

16. Listen to the answers and show interest. Clarify where needed. Be open and non-judgmental until you have all the facts you need. Then you may provide a balanced decision or opinion. Nervous people make errors, miss-statements, or exercise poor judgment - make allowance for the “fear factor”. Maintain focus on your goals and agenda. Your duty is to complete the audit and provide a balanced cGMP assessment. Give praise where it is due and recognize good work. Maintain a sense of self esteem and reward competence and expertise when/where appropriate. Auditors Behavior Continued…

17. Keep an accurate record of events, findings, and facts. Take the time necessary to take good notes. Ensure audit objectives are maintained. – Keep one eye on the clock, and the other on your agenda. Respect Confidentiality. You will be in possession of sensitive or confidential information : do not discuss it outside of the audit!. Auditors Responsibilities

18. Don’t lose your temper Be confident of your facts by using standards to back you up. Know your standards, and be willing to refer to them. Do not argue at any time. Auditees may argue, but auditors discuss. Smile, break up the atmosphere, relax the auditee. It’s OK to have a sense of humor ; actually, it will build bridges between you and the auditees. Time wasting, unrelated side conversations long lunch times, frequent break requests. Identify these diversions and politely address them. – This can be a little difficult. Don’t make it seem like an insult. Evasive or indirect answers. Difficult situations may arise

19. Pay attention to body language – both theirs and yours. Superiority, hostility, contempt, concern, anger, boredom, fatigue, confusion, apathy, fear and nervousness, can all be visually communicated without words. But, be careful!!! Sometimes it may be necessary to clarify the response you receive. Be willing to re-phrase a question. Ask the auditee to expand upon their answer. Repeat the question when necessary. Language barriers can require even greater tolerance. Be aware of potential misunderstandings, and be patient. Be clear in your message. Strive for clarity and simplicity with every question. Communications

20. Communications Be aware of cultural differences. Respecting these differences builds bridges between people. LISTEN to what the auditee is saying !!!! Don’t formulate your next question while listening to an answer. Focus on one topic, one conversation, at a time. Avoid distractions, which can include : Thinking ahead to the next question. Listening to side conversations. Verbal overload from the auditee may dilute the true response. You have 2 ears and 1 mouth – use them in that ratio.

21. QUALITY AUDIT Preparation and Planning

22. Audit Planning Communicate the Audit Plan Selection of Auditors Preparing for Audit Pre-audit Information Planning and Preparation

23. Audit Plan The audit plan is a formal document, which covers every area, process and department for the audit activity. It specifies : The area, process or department to be audited. The frequency of the audit, preferably the month in which the area, process or department will be audited. Audit Planning

24. Schedule : The audit schedule is a document that gives details of the area, process and department to be audited during the scheduled audit. It also specifies dates of audit, names of auditor and corresponding auditee area, process or department. Timing : The best time to audit is when people are at their busiest and tempted to take short cuts or make mistakes. However convenience of the auditee is essential and their readiness and concurrence should be determined before proceeding on an audit. Audit Planning Continued…

25. Audit Frequency Based on criticality of area / process to be audited. Based on quality history of the area to be audited. General self inspection program at defined frequency. Can be influenced by upcoming regulatory events (e.g., audits, complaints/recall, follow-up, compliance etc.) Do not agree to frequent requests for postponements or cancellations. Emergency audits probably be added to your schedule at short notice. Do not over schedule yourself, otherwise emergencies will destroy your carefully crafted schedule. Facility / area upgrade / shutdowns will impact your schedule – preview upcoming maintenance plans and work around them. Audit Planning Continued…

26. Ensure that the schedule is communicated to all site personnel, especially those whose areas will be audited. Clearly list the areas / systems / products to be audited and list specific dates for each of the audits. Realistically establish and agree each audit’s duration. Adhere to the schedule – don’t risk loosing credibility by postponing audits. Communicate the Audit Plan

27. Based on educational qualification, industrial experience, in-house / outside trainings and technical knowledge of the individual. People within the organization who have been trained to conduct audits. This training can be done by the organization it self if expertise exists within and there can be one auditor per department. Important precaution to be taken is to ensure that people do not audit their own area. (because that would make them biased). Auditors must treat audit as a fact finding exercise and so should do a professional job. Selection of Auditors

28. Prepare and send detailed agenda, objective and scope of the audit. Know your standards. Ensure that auditee is well aware of the standards you will be using during the audit. Prepare a detailed checklist. - Checklist's are methodical way of ensuring that all necessary areas are audited and right question asked. A checklist is therefore useful tool. - However the auditors should adopt a flexible approach and use their own judgment to deviate, if necessary. Preparing for Audit

29. Activities performed by auditee Site master file Quality Manual Review the layouts Understand the men material flow Pre-audit Information

30. Need Break?

31. Performing the Quality Audit

32. Contents The opening Meeting The site / Area tour Beginning the Conference Room audit Auditing Techniques Questioning Techniques The Daily Wrap up Classification of Audit Observations The close-out meeting. Performing The Quality Audit

33. This is your first point of face-to-face contact with auditee. Needless to say, Be on time . Exchange business cards (recommended for outside audits) Each side introduces the attendees - Each auditor introduces him/her self. - Ensure that you clearly understand roles and responsibilities of auditees Try to remember names for use during the audit – People like to have their names remembered. Re-confirm the agenda. Modifications / changes if agreed by both the sides. Site / departmental presentation. Make note of important information. Use brief presentation to brief yourself (recommended for outside audits) The Opening Meeting

34. The Site / Area Tour A very critical part of audit. Respect dress codes of the areas to be visited. Ask for help / clarification for your gown. Always view the workers gowning area. Do not be afraid to ask to visit controlled areas. Allow one auditor to speak at a time. Talk to workers during site tour. Ensure that you understand the answers. If not ask the same question again. Ask for clarification if required.

35. Keep all senses open Smell, Sight, Hearing, Touch, Taste Stay close to agreed plan of the tour Try not to get distracted and lose time. Be willing to stop and focus on an area of non-compliance Keep a record of documents requested during tour. Let your host know that you are keeping a record of all requests. Go back into the GMP areas again towards the end of the audit. Have things changed? Are things being done differently? The Site / Area Tour Continued…

36. The Site / Area Tour Continued… Are supervisors “supervising?” Check the condition of the building(s) – are surfaces appropriate? Cleanliness of the areas, equipments and materials transported. Are gowning regimes appropriate and honored? Are doors shut when not in use? Are pressure differentials monitored and compliant? Are rooms, products and containers clearly labeled? Are SOPs available for operator? Is appropriate pest control in place? Are logbooks maintained?

37. Beginning the “Conference Room” Audit Don’t concern about number of people in the room – but, limit attendance to only those people necessary. Try to relax yourself and everyone else. Set a good, efficient work pace. Allow reasonable breaks. Stand up from time to time, stretch, get a drink and restart. Break the monotony!!

38. Conference Room Audit You can open conference room audit in one of the following way: The first item on your agenda. Your list of documents requested during tour. The cGMP violations seen during tour. By asking questions relating to the documents you analyzed before the audit began. Production / process record review. (Batch record, supporting SOPs, Personnel training etc.) Or just start at the beginning of the process flow.

39. General Techniques Horizontal – just skimming the surface! Vertical – in depth, be sure on how far do you dig? Combination of the two, stepwise digging where necessary to return again to the surface. Auditing Techniques

40. Horizontal Auditing Follows a process from goods receipt through to finished product release and distribution. A good way to get a “feel” of the site and its problems. Auditing Techniques Continued… Vertical auditing Good to help identify the severity of a specific issues. Can be time consuming. You need to know when to stop. Focuses deeper and deeper into a specific area, product, or problem.

41. The Ideal Combination Ideally a cGMP audit should include mostly horizontal auditing with occasional vertical auditing when possible issues are noted or something does not “feel” right. Auditing Techniques Continued…

42. The Beginning to End technique : Start at the beginning of the process, and follow the work/process through to the very end. Provides the auditor with a progressive, detailed view of the process and requirements. Batch records simplify this approach. Most common approach to process auditing. The End to Beginning technique : Good for assessing complaints, lab failures, reworks, etc. Begin with a known problem and trace it back to its origin. Generally a focused approach leading to root cause analysis. Auditing Techniques Continued…

43. Random sampling – good when limited time, gives a “feel” and flexibility (good notes are needed for later description). But regardless of which audit you do, always review the related documentation. Record all of the details as accurately as possible, including : What Where When Who Why (if any issue) Auditing Techniques Continued…

44. Open questions : How do you perform this process? Can you describe site’s GMP training program? What is your program for HEPA filter certification? Open questions require a factual, detailed response by the auditee. The answers to your open ended questions will tell you if the auditee understood the questions. Creates a dialog between the auditor and the auditee. The auditee begins to understand what it is you will be asking for, and becomes better prepared to provide it = a great time saving device. Generally, one open ended question will lead to another through the dialog process. Questioning Techniques

45. Closed questions : Are products manufactured using batch records? Are the operators responsible for entering process data into the record? Are the operators also responsible for recognizing and recording deviations? Closed questions require a simple “yes” or “no” from the auditee. The answer does not allow you to judge if the question was fully understood (or miss understood) by the auditee. Does not promote a dialog between the auditor and the auditee. You must engage the auditee in order to realize the full benefits of the audit. Requires that the auditor follow up with a second or third question. Forces the auditor to do all of the work. Questioning Techniques Continued…

46. Ask a combination of open and closed questions : Q : Do you have a system for recording and addressing deviations? A : yes, we do. Q : Excellent. Would you please describe how the system works? Q : Who is responsible for registering deviations that occur during the manufacturing processes? A : The operators are responsible for recording any deviations. Q : Is that both production and packaging operators? A : Yes. Q : Could please tell me how you train your manufacturing operators to recognize a deviation? Questioning Techniques Continued…

47. Clarification and Confirmation If your question was not understood, you can Repeat the question. Re-phrase the question for clarity. Use an example to further clarify the question. Draw a diagram (don’t laugh ! This really works!). Ask yourself, “Is it time for a break”? Follow up selected questions with a “show me the evidence” request. Request documentation for critical points. Request documentation if you think that you may not be receiving correct information. Request documentation periodically throughout the audit, for both “small” and “large” points. Questioning Techniques Continued…

48. Require / Request a daily wrap-up meeting Include the audit escorts and day’s participants at a minimum. Do not categorize the issues (as Critical, Major & minor) – more of the same issues tomorrow may make the observation more severe. Discuss observations found during the day. Give the site a chance to correct them or to provide more evidence to support their defense. Daily meetings promote understanding and prevent surprises at the final wrap-up. Clarify any follow-ups for tomorrow and tomorrow’s agenda. The daily wrap-up provides clarity and keeps the auditee engaged in the process. The Daily Wrap-up (For multiple day audits)

49. Critical? Major? Minor? CRITICAL Patient risk, or no key system in place (e.g. no deviation system), or a condition which may make the product unfit for use, or a condition which may be cited by regulatory authorities as critical following an inspection, or where previous major audit findings had not been suitably addressed by the site. A critical issue could require further operations to stop until corrective actions have been implemented. Classification of Audit Observations

50. MAJOR : Significant problem in plant or systems which lead to non life threatening conditions, or system not functioning properly with several similar observations noted. These problems will most likely result in a citation by regulatory authorities. Previous minor audit findings can be considered as major if they have not been suitably addressed by the site. MINOR : Isolated problems that if not corrected, would not cause harm to the patient or product, but indicate minor breaches to GMP. If significant numbers of remarks are made in one system area, it could be indicative of the start of breakdown in a system and therefore classified as Major. Classification of Audit Observations Continued…

51. Thank the auditees for their help and time. List the good things that you saw or found during the audit. Present the Criticality of the observations highest first. Focus on the Critical and Major findings. Add minors if there are not too many findings in total. Present findings based on facts, and back the findings up with information contained in the standards, if questioned. Respond to questions openly at end of the audit. Be prepared to change your wordings or even observations based upon facts presented by auditee(s). The Close-Out Meeting

52. Audit Report and Follow-up

53. Why do we write an audit report? As a record of site/departmental deficiencies. To provide the Site Management Team with an independent report of deficiencies identified. To create the formal environment necessary for an active, periodic follow up. How do we write an audit report? Include positive points as well as deficiencies identified. Management must have a balanced overview of conditions within the plant; therefore, provide them information on areas of strength (best practices) and areas requiring improvement. When do you write an Audit Report? As soon as you possibly can after conclusion of the audit. Before you begin your next audit. Before you forget where you were and what you observed. Reporting Audits

54. Complete the audit report. Commit to a time of delivery, and stick to it. Compile the observations and add to the end of the report. Send the audit report and observations with a cover letter or a cover e-mail to the auditee. Ensure that you include firm instructions for reporting corrective and preventive actions back to you. Provide the easiest and most convenient reporting format, such as Word/Excel table. If you require hard copy documentation to prove observation close out, arrange for its proper transfer to your office. Ensure that you have self notification process that can tell you when someone is overdue for reporting corrective actions. Follow-up with late responses on a personal basis. Elevate non-response to observations to the next management level. After the Audit

55. Remember!! Performing the audit is the easiest part of the audit process. Successfully completing a timely and thorough audit observation follow-up is the most difficult and time consuming facet of the audit. Ensure through your persistence, tenacity, a sense of efficient organization, that you follow each observation through to its final, cGMP compliant conclusion. Never give up!

56. THANK YOU