inspection-readiness for Pharmaceuticals

inspection-readiness

1. 1
Inspection Readiness
Training
DR. Md. Zahurul Hossain
GM, Quality Operation Division

2. Slide 2
Agenda
1.Introduction
2.What can we do to prepare?
3.Individual interactions
4.Investigative Techniques
5.During the Inspection
6.Final notes

3. Slide 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. 4
1. Introduction

5. Slide 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. Slide 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. Slide 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. Slide 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. Slide 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. Slide 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. 11
2. Site Preparation

12. Slide 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. Slide 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. Slide 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

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

16. Slide 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. Slide 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. Slide 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. Slide 19
Roles & Responsibilities
Inspection Escorts
–Accompany the Inspector at all timesensuring
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. Slide 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. Slide 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. Slide 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. Slide 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. Slide 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. Slide 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. Slide 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. Slide 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. Slide 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. Slide 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. 30
3. Individual
Interactions

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

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

36. 36
4. Investigative
Techniques

37. Slide 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. Slide 38
Investigative Techniques
1.Silence
2.Open Ended Questions
3.Fishing Trips
4.Redundant Confirming Questions
5.Hypothetical Questions
6.Eye Contact and Body Language

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

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

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

49. Slide 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. Slide 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

51. Slide 51
Investigative Techniques:
Example –Hypothetical Question
•Inspector: “What would you do if a
machine broke down?”
•Operator: “Oh that would never happen.
We take really good care of our
machines here. We have a great
preventative maintenance program that
I supervise.”

52. Slide 52
Investigative Techniques:
Example –Hypothetical Question
•Inspector: “What would you do if a machine
broke down?”
•Colleague: “Procedures for operating this
piece of equipment and what to if there are
interruptions are defined in SOP xxx” or
“As SOP xxx states, I would contact the
area supervisor.”

53. Slide 53
Investigative Techniques
•Be honest and relax
•If you think you made a
mistake, work with the
escort to assure mistaken
information is taken care
of in an appropriate
manner; offer to contact
the appropriate resource
to get the correct answer
6. Eye contact and Body Language

54. Slide 54
Investigative Techniques:
Example –Body Language
•Inspector may ask an operator a question while they
are working near a production line.
–Do not pretend like you cannot hear them because the
machinery is too loud or avoid eye contact so that they will
not speak with you.
–This looks like avoidance and will be viewed as suspicious
behavior.
•For example, an Inspector enters into the
manufacturing area and slowly all operators leave the
area and exit into the packaging area to avoid being
questioned by the inspector

55. 55
5. During the
Inspection

56. Slide 56
Key Points
•Tour
•Thing to do / not to do
•Implementing Immediate Corrective
Actions
•Daily Debriefing Meetings
•Concluding the inspection
•Follow up action Items

57. Slide 57
Tour
•Those colleagues who are associated with
the route should be notified that it is about to
commence
•The escorts must remain with the inspector at
all times
•If the inspector wishes to look in another area
that is not on the ‘planned’ route then those
‘other’ areas can also be toured
•Detailed notes should be taken

58. Slide 58
Things TO DO
•Act in a professional manner
•Show an interest in their recommendations and comments
•Let them talk and listen carefully
•Provide prompt and courteous responses
•“Politely” point out published references to support your policy
and practices
•Ask the Inspector to point out observations as they are noted
•Try to determine the point of the observation or concern
•Research the situation and formulate your response
•Present your response at the appropriate time; e.g. end of the
day
•If answering quantitative questions -Inform the inspector that
you will provide an answer after reviewing the appropriate
records

59. Slide 59
Things NOT TO DO
•Be nervous
•Lie to the Inspector
•Interfere with the Escort/Inspection Team
•Argue or extensively debate with the Inspector
•Argue with others when the Inspector is present
•Answer “off-the-record” questions
•Guess or provide approximate answers
•Correct other people in front of the Inspector
•Interrupt someone else’s answer
•Interrupt the Inspector’s comments and explanations
•Provide your opinions
•Answer for someone else
•Answer questions that do not pertain to your department or
operations
•Use the Inspector as your consultant

60. Slide 60
Things TO DO
–When reviewing Records
•Provide general assistance with the
format of the records
•Locate the information or data that
addresses the Investigator’s question or
request
•Have an expert or the responsible
person available to answer
follow-up questions

61. Slide 61
Things NOT TO DO
–When reviewing Records
•Point out errors
•Correct errors during the review
•Comment or “apologize” for the quality of the
data
•Comment on plans to improve recordkeeping
practices, unless criticized by the Investigator
•Make constant references to planned SOP
revisions, unless criticized by the Investigator
•Provide a detailed explanation/ translation,
unless specifically requested

62. Interview Dos and Don’ts
Do:
•Answer all questions honestly;
•Say “I don’t know” or “I’ll get the answer for
you;”
•Avoid such phrases as “I think,”
“Sometimes/often/usually,” “never” and “next
time;”
•Avoid qualifiers, such as “typically,” “normally,”
“generally” and “usually;”
Slide 62

63. Interview Dos and Don’ts
Do:
•Stop speaking once the question is answered;
•Ask for explanations or interpretations of what you do
not understand;
•Maintain a friendly and cooperative attitude;
•Control your temper; remain courteous and
professional; and
•Maintain eye contact.
Slide 63

64. Interview Dos and Don’ts
Don’t:
•Volunteer information or answer a question
that hasn’t been asked;
•Be sarcastic;
•Guess answers;
•Attempt to answer “what if?” or hypothetical
questions;
•Argue with an investigator;
•Philosophize, ramble or editorialize;
Slide 64

65. Interview Dos and Don’ts
Don’t:
•Point out deficiencies or errors;
•Apologize for problems or comments made by
an investigator;
•Feel the need to respond to every comment
made;
•Become defensive or evasive;
•Look away, fidget or look nervous; or
•Make statements about your personal opinion
of the FDA.
Slide 65

66. Slide 66
Implementing Immediate
Corrective Actions
•A systematic approach should be taken here
and interdependencies considered
•It should be ensured that the corrective
actions do not conflict with other methods,
procedures or policies
•All change control procedures should be
followed
•Creating new problems should be avoided
•Shortcuts should not be taken
•Global Implications should be considered

67. Slide 67
Implementing Immediate
Corrective Actions
•Observations noted by the Inspector
that are readily correctable shall be
corrected as soon as possible
(preferably before the close of the
inspection).
•The inspector should be requested to
note the corrections in their report

68. Slide 68
Daily Debriefing Meetings
•Listen carefully
•Any concerns should be addressed the
next day rather than contesting them at
the debriefing
•Time of return the following morning
should be confirmed
•Any preparations required to move the
inspection along should be established

69. Slide 69
Concluding the Inspection
•The Exit meeting should include only key
participants and S-QRT members
•Colleagues should attempt to fully understand
any observations made by the Inspector
•If there is disagreement with points raised by
the Inspector, these opinions should be
politely expressed as well as in subsequent
written responses

70. Slide 70
Concluding the Inspection
•Colleagues should avoid committing to
specific actions to the Inspector during
exit meeting
•A designated colleague shall be
identified to submit a written response
to the inspector/ authority within the
agreed timeframes

71. Slide 71
Follow up actions
•A written response to the report should
be drafted by the Site Quality Authority,
reviewed and agreed to by the SQRT.
•Responses to Regulatory audits are
also submitted to the responsible
QOAL, responsible Manufacturing Team
Leader, and VP Global Quality
Operations, for review and approval.

72. 72
6. Final Points

73. Slide 73
Remember!!
•Gain the inspectors trust, through
•Planning
•Organization, and
•Professional behavior

74. Slide 74
Desired Inspection Outcome
The inspector leaves the site thinking that we are
professional, knowledgeable, competent i.e. we are
doing the right thing for our customers and operating
in a state of control
–All documents and data requested were presented
to the inspector is good time
–All documents and data were complete and
correct, and adequately addressed their concern
–There was no antagonism / arguments between
the inspector and the site colleagues
–There was a controlled and efficient
atmosphere

75. Slide 75
Summary
•Individual actions can have a large effect on
the investigator’s perception of our company
and on the inspection’s outcome.
–Do your preparation
–Know what you are responsible for
–Be professional and courteous
–Only answer what is asked
–Understand all questions clearly before answering
–Remain calm!

76. Slide 76
Questions ?
Please complete your
training record and your
learning evaluation