Inspection Readiness Training

1. Inspection ReadinessTraining Victoria Niven Global Quality Operations Training and Program Development

2. Agenda • Introduction • What can we do to prepare? • Individual interactions • Investigative Techniques • During the Inspection • Final notes

3. Learning Objectives At the end of the training you will be able to: • Define general inspection preparation activities • Define the Dos and Don'ts of interacting with inspectors • Identify different investigative techniques • Define actions to be taken during the inspection

4. 1. Introduction

5. Inspector Responsibilities • In general, inspectors assess compliance to relevant GMP references /cGMP expectations and issue a detailed report. • Pfizer Auditors may also provide advice / guidance

6. Inspector Preparation • A regulatory inspector may review some of the following in advance : • Company file held by the regulatory authority • Site Master File • Manufacturing Licence • Registration Dossiers • Previous inspection records • A Pfizer auditor: • May ask you complete a client profile • Have a pre-audit teleconference

7. Inspector Preparation • Regulatory inspector may ask to receive some of the following in advance: • Annual financial report • Complaints file • Questionnaire providing specific information about the company • Layout of site and diagrams • Manuals • Standard Operating Procedures

8. Inspector Preparation • Some inspectors may prepare a checklist or aide-mémoire • A general outline or program will also be drafted. • Should be used to ensure the right people are available

9. Methods of Fact Finding • Trace Forward • Follows the production flow from receiving starting materials to dispatch of product from the warehouse. • Trace Backward • Review the history of a batch through the various processes • Random • Start from points around the factory that appear to be significant. The inspector chooses which method, but the Trace Forward is the most common method.

10. Taking Notes • The inspector will take notes, writing: • Details and facts (will trust but will verify) • Specifics, not generalisations • Specific records will include: • Names of persons interviewed (and job titles) • Document numbers and who receives them • These people may be then be interviewed • Equipment numbers • Item identification • Layouts • Obvious non-conformities

11. 2. Site Preparation

12. Preparation - Leadership • Pick an audit team and define their responsibilities • Allocate rooms • Inspection Room (where the inspector will be based) • Back Room (where we prepare and hold relevant documents) • Ensure that documentation is prepared • See List • Ensure that colleagues are trained and understand their responsibilities • Ensure each area is clean and compliant (housekeeping) • Ensure that there is a sign at the entrance advising that no cameras or video equipment are allowed

13. Preparation- Who Should be Involved • Managers and Leaders should be prepared to answer questions on work that is done in their areas of responsibility • Any colleague may be asked to explain what work they are doing

14. Copy of registrations under review during the inspection. • Product specifications • Site master file (in the case of EMEA inspections, this should be provided to the inspection team as far in advance as possible). • Index (list) of all SOPs used by the site • Translations (where necessary) of critical SOPs, including those describing the handling of OOS results, deviations, media fills, change control, SOP management, training, environmental monitoring, etc. • Qualification dossier for any contract laboratories or packagers used. • List of lots manufactured for the market of interest during the inspection, including the date of manufacture for the previous 12 months. • List of deviations since the previous inspection with translated titles. Have associated deviation investigation files on hand as well. • List of OOS results (both initial and confirmed) for the last 12 months. Have associated OOS investigation reports on hand. • Most recent Product Quality Reviews / Annual Reviews. • Technology Transfer Reports (where appropriate) • List of major changes to the site (organization, facility, equipment) • Environmental monitoring and water testing quarterly reports and trending data. • Product development report (in the case of pre-approval inspections). • Complaint files • Process flow charts and diagrams • List of batches on stability for the market of interest. Be prepared to present stability failures and associated investigation reports. • If applicable, list of media fills from the last two years and their results. Have media fill batch records and any associated investigation reports on hand. • Approved WFI, HVAC, (and other critical utility) system drawings. • List of critical equipment used in manufacturing. Have validation (IQ/OQ/PQ) reports available. • List of all computerized systems used in any aspect of production and associated computer system validation reports • Cleaning validation reports General Documents – amend as appropriate

15. Audit Team Roles & Responsibilities • Initial Contact • Inspection Escorts • Scribes • Runner • Back Room Administrator • Subject Matter Experts

16. Audit Team For each inspector there should be: • 1 escort • 1 runner • 1 scribe !!! Important !!! At no time can an inspector be on their own.

17. Roles & Responsibilities Initial Contact • Security must • Greet the Inspector(s) and sign them in as a visitor (with badge) • Notify the Site Quality Authority representative • Initial Site Quality Authority contact: • Greets the guest and verifies the sign in • Escorts inspectors to designated meeting room • Conduct introductory meeting with designated participants

18. Roles & Responsibilities Initial Contact • During the Introductory Meeting • Extend normal business courtesy • Request Inspectors agenda indicating purpose, scope and expected duration of the inspection • Develop / agree on tentative schedule for the inspection • Present overview information on the site

19. Roles & Responsibilities Inspection Escorts • Accompany the Inspector at all times ensuring designated attire for the area is provided • Set the tone & maintain courteous and professional attitude • Ensure that all questions are within the scope of the audit • Introduce the Inspector to others • Be present during all interviews & discussions • Assist in ensuring that colleagues understand the questions

20. Roles & Responsibilities Inspection Escorts • Remain in contact with management • Communicate with the scribe and runner • Manage time and logistics • Enforce company rules • Ensure that identical samples are taken at the same time the samples are collected for the Inspector

21. Roles & Responsibilities Inspection Escorts • Manage the document review and interview phase in the inspection room. • One document at a time to the inspector • When finished with the document, take it away and then present the next document • If this process does not run smoothly you will quickly lose control

22. Roles & Responsibilities Inspection Escorts • Do not keep the Inspector waiting • Do not engage in stalling tactics • Do not refuse to produce a record because the Inspector does not request it using the your terminology (e.g., “batch” Vs. “production” records)

23. Roles & Responsibilities Scribe • Crucial part of the audit – cannot rely on memory • Take detailed, real time notes • Provide a detailed, dated listing of all documents, samples or other items reviewed by, requested by, and/or provided to the Inspector • Record who, what, when, where during the audit • Summarize topics covered during the day • Include a list of potential observations or inspector concerns • Note: Keeping notes is important for all audits, however the distribution of the daily notes is different

24. Roles & Responsibilities Scribe –Taking notes • Avoid long descriptive text • Use key words • Don’t write anything down unless you understand what you are writing • Draw diagrams/pictures • Rewrite / finalise notes as soon as possible

25. Roles & Responsibilities Runner • Accurately document and track every request made by the inspector • Ensure requested information and documents are given to the back room administrator, ready for logging and taking to the inspector

26. Roles & Responsibilities Subject Matter Expert • Have extensive knowledge of policies, procedures, operations, and organizational structure for their area • Have the authority to access all information • To be able to communicate and explain clearly and rationally

27. Roles & Responsibilities Back Room • One individual designated as the Administrator, to: • Contact necessary personnel • Ensure that all colleagues who have been requested by the inspector pass through the room for preparation • Maintain a list of those being interviewed • Ensure that the colleagues are informed about what he/she can expect during the interview and if possible where the line of questioning is leading • Make the colleague feel relaxed and well prepared • Debrief colleagues post interview

28. Roles & Responsibilities Back Room • In addition, the back room administrator must: • Track all outstanding inspector requests and their status • Review the documentation the colleague has brought with them to ensure it is really what the inspector wants • Acquire duplicate copies (or reference controlled systems) of items given to the investigator • Ensure all confidential documents provided are marked ‘CONFIDENTIAL’ • Catalog all requested documentation

29. Materials & Equipment • Copiers, Fax, Phone • Computers • Flip charts • Stapler/Staple remover • Notepads • Clipboard • Regulations and references • Log Document Request • Paperclips • Confidential & Uncontrolled Copy Stamp • Extra ink

30. 3. Individual Interactions

31. Individual Preparation • Make sure areas are neat and clean and professional • Ensure organization charts are up-to-date • Ensure that all documents are properly controlled • Locked areas should be locked • Reagents, solvents, disinfectants should be properly labeled • Equipment status should be clearly identified • Recording charts and logbooks should be appropriately reviewed and signed.

32. Individual Preparation – Underlying Questions • Do you know what you are doing? • Do you know why you are doing it? • Do you have evidence to show you have done it correctly? • Is everything under control? • When something goes wrong, how do you correct the problem and how do you prevent it from happening again?

33. Interacting with Inspectors • Pfizer’s policy is cameras and recorders are not allowed during a inspection (should have a sign at reception) • If an inspector insists on using cameras & recorders, discuss this with site / regional leadership to make the decision.

34. Body Language What is the % for Total Communication? Body = ____% Voice = ____% Words = ____% Total = 100%

35. Interacting with Inspectors What does your facial expression say about you?

36. 4. Investigative Techniques

37. Investigative Techniques • Be Aware of interviewing techniques to: • Obtain additional, volunteered information • Validate –or- invalidate information already gathered • Compare / contrast information • Test knowledge or understanding • Identify potential issues or concerns • Assess honesty, integrity, credibility

38. Investigative Techniques • Silence • Open Ended Questions • Fishing Trips • Redundant Confirming Questions • Hypothetical Questions • Eye Contact and Body Language

39. Investigative Techniques 1. Silence • Strategic pause – “whoever speaks first loses” • Allow the inspector to make the next statement – keep quiet

40. Investigative Techniques:Example – Silence: • Inspector: “What is the test you are currently performing? • Analyst: “An HPLC assay for a new product.” • Inspector: Silence and staring ……………………………… • Analyst: (feeling awkward)….and, em, this is the first time I’ve done this assay by myself. It’s difficult to perform. See all these sample dilutions I have to make. Takes me all day. But, of course, I won’t be staying late today because I’m in the soccer final. John said he’d take over and…..(escort cuts in and ends the conversation).

41. Investigative Techniques:Example – Silence: • Inspector: “What is the test you are currently performing? • Analyst: “An HPLC assay for a new product.” • Inspector: Silence and staring ……………………………… • Do not continue on with your answer. It is okay for there to be awkward silence in this instance. Wait for the inspector to ask another question or move on.

42. Investigative Techniques 2. Open Ended Questions • Inspector’s goal is to get excessive and volunteered information • Ask for specificity and answer the specific question, don’t elaborate

43. Investigative Techniques:Example – Open Ended Questions • Inspector: (observing an analyst performing a test method) “What difficulties do you encounter with this method?” • Colleague: “Well the machine is quite old, so sometimes this lever sticks. Other times, if the humidity is high in the lab, then the product will stick to the inside of the container, and ………..”

44. Investigative Techniques:Example – Open Ended Questions • Inspector observing an analyst performing a test method: “What difficulties do you encounter with this method?” • Colleague: “I perform sampling according to SOP XXX. If there are any difficulties I refer to SOP YYY. • Escort or Supervisor: Try to get them to focus the question by asking them to explain further what type of information they are looking for.

45. Investigative Techniques 3. Fishing trips • Inspectors like to open cans of worms • Try to specify • Provide the information requested, no more and no less • If you do not know the answer, defer to the escort

46. Investigative Techniques:Example - Fishing Trips • Inspector: “Can you show me your complaint file?” • Colleague: “Sure. Let me show you where we keep it. The document manager there can get you a copy of any one that you would like to see”

47. Investigative Techniques:Example - Fishing Trips • Inspector: “Can you show me your complaint file?” • Colleague: “I would be happy to. Could you tell me what product or production area you would be interested in?”

48. Investigative Techniques 4. Redundant confirming questions • Do not rush, think before you answer • Stick to your original answer, do not elaborate

49. Investigative Techniques:Example – Redundant Questions • Inspector (looking at a scale): “How would you go about cleaning this piece of equipment?” • Colleague: “The scale is cleaned as per SOP xxx.” • Inspector: (At an additional scale of the same make in the laboratory) “To clean this piece of equipment you would wipe it down with alcohol correct?” • Colleague: “This scale is also covered by SOP xxx.”

50. Investigative Techniques 5. Hypothetical questions • When asked a hypothetical question about a work process, respond by referring the particular procedure. • Try and keep the discussion realistic based on actual facts or history. • Don’t play the “What If” game as this may introduce “unreal” concerns