1 gmp inspection process introduction. 2 programme objectives 1.familiarise with gmp inspection...
Post on 23-Dec-2015
225 Views
Preview:
TRANSCRIPT
2
Introduction
Programme Objectives
1. Familiarise with GMP inspection 2. How to perform an inspection3. Developing an action plan
3
Inspection
Programme Overview• Introduction• The fundamentals of inspection
– the role of the inspector– preparing for inspections– the inspection process
• Types of inspection
4
Inspection• These guidelines may be useful to inspect
production and control of:– final dosage forms
• human and veterinary use
– drug substances• API and bulk drug substances
• Same fundamental principles:– pharmaceutical products– including biological products– also medical devices and– diagnostic products
5
Inspection
• Inspection and licensing:– vital element of drug control– WHO Certification Scheme on the
Quality of Pharmaceutical Products moving in International Commerce (see last Semester! It contains statement on GMP inspections!)
6
Inspection
• Other contexts (using the word „inspection” in a broader meaning):– self inspection of the company– independent inspection by persons e.g. from
the International Organization for Standardization (ISO)
– audit by authorized agents of a customer
7
Inspectorate• Enforcement arm of the National Drug
Regulatory Authority (DRA)• Functions:
– Ensure adherence to licensing provisions– Adherence to GMP
• Objectives:– Control and enforce standards
• through sequential examination (production and control)
– Recommend authorization of manufacture of pharmaceutical products
• verification of performance• verification of data
9
The Role of the Inspector
Qualifications• Training• Practical experienceIn pharmaceutical manufacture and/or
quality control
• Academic qualifications– pharmacists, chemists, scientists– pharmaceutical industry background
10
The Role of the Inspector
Training• In-post training• Accompany experienced inspectors• Regular update of knowledge • Courses and seminars
– pharmaceutical technology– microbiology– statistical aspects of quality control
11
The Role of the Inspector
Responsibilities 1• Detailed factual report
– manufacture and control– specific products
• Assess GMP compliance– faults, irregularities, discrepancies
12
The Role of the Inspector
Responsibilities 2• Advice on improving manufacture
and control– depending on national policy– must be consistent and available to all– motivate manufacturer to comply with
GMP– correct specific deficiencies
13
The Role of the InspectorPersonal Qualities
• Conform to codes of ethics and conduct• Independent/no conflict of interest• No double role as inspector and
consultant• Resist attempts to influence decisions• Discrete
14
The Role of the Inspector
Communication Skills• Language• Body language• Company history and policy
16
Preparation for an Inspection
Scope of Inspection• Objective• Type • Depth• Timing• Inspectors:
– size of team– make-up of team
17
Preparation for an InspectionNotification
• The company being inspected• Team members
– expert support– other inspectors
• Other interested parties
18
Preparation for an Inspection
Review documentation from Regulatory Authority
• Company file• Site Master File• Manufacturing licence• Registration dossiers
19
Preparation for an Inspection
Review documentation from Regulatory Authority
• Reports– Adverse Drug Reaction reports (ADRs)– Previous inspections
• Records– Complaints and recalls– Regulatory test results (surveillance)
20
Preparation for an Inspection
Review documentation from the manufacturer
• Annual report• Complaints file• Self inspection/internal audit reports• Send a questionnaire to the manufacturer asking
to provide specific information about the company• Layout of site and diagrams• Manuals• Standard Operating Procedures
21
Preparation for an InspectionProgramme
• Checklist• Aide-mémoire for inspection• Develop inspection programme• Distribute inspection programme
– Company– Team
22
Preparation for an Inspection
Possible Issues – IThe first inspection of a new
manufacturer• Plant design and equipment• Processes• Documentation• Personnel• Quality control
23
Preparation for an Inspection
Possible Issues – IIRegular inspection of an established manufacturer
• Actions arising from the previous inspection
• Areas not previously inspected• New areas, processes and products
24
Preparation for an Inspection
Possible Issues – IIIInspection because of complaints
about a product• The product in question• Manufacturing process• Premises• Systems for handling complaints and
recalls• Quality control records
26
Types of GMP Inspection
Objective of the inspection
• Routine inspection• Concise (abbreviated) inspection• Follow-up inspection• Special inspection• Quality systems review
27
Types of GMP Inspection
Routine Inspection• Full inspection of all components of GMP• Newly established manufacturer • Renewal of a license• Changes:
– new product or product lines– modifications to manufacturing methods– key personnel, premises or equipment
• History of non-compliance with GMP• Not inspected in the last 3 -5 years
28
Types of GMP Inspection
Concise Inspection• Consistent record of compliance with GMP• Focus on limited number of GMP
requirements– selected as indicators
• Identify significant changes• Indicate attitude towards GMP• Non-compliance:
– should trigger comprehensive inspection
29
Types of GMP Inspection
Follow-up Inspection• Reassessment or re-inspection• Monitor result of corrective actions• 6 weeks to 6 months after initial inspection
– nature of defects– work undertaken
• Specific GMP requirements– not observed
• not adequately implemented
30
Types of GMP Inspection
Special Inspection• Spot check focusing on:
– one product, a group of related products– specific operations e.g. mixing, labeling
• Complaints or recalls• Adverse Drug Reactions• Marketing approval or export certificate• Information or investigation:
– specific information– advise on regulatory requirements
31
Types of GMP Inspection
Quality Systems Review• Assess the quality assurance (QA) system• Description of the QA system (e.g. manual)• Policy and standards to be observed• Management structure
– implementation
• Procedures– quality standards set for products– correctly defined manufacturing processes– records kept– QC and QA functions are performed
32
Types of GMP Inspection
Frequency of Inspections• Depends on type of inspection• Inspectorate resources (e.g. workload, number
of inspectors)• New facilities - before licensed• All companies - regular schedule
– ideally annual
• Large companies– several visits over a period e.g. 5 years– validity of manufacturing license or GMP certificate
33
Types of GMP Inspection
Duration of Inspections• Depends on type of inspection• Inspectorate resources (e.g. workload,
number of inspectors)• Size of the company• Purpose of the visit• Days to weeks• Number of inspectors
– including specialist support
34
Types of GMP Inspection
Announced and unannounced inspections
• Depends on type of inspection• Announced:
– comprehensive inspection
• Unannounced:– routine inspection (depending on country policy)– concise inspection– follow-up inspection– special inspection
35
Types of GMP Inspection
Regulatory Actions• Based on national regulations• Correction of unsatisfactory
situations• Closing down of a factory• Withholding of authorizations• Product recall
37
Timetable• Entry briefing/opening meeting• Orientation tour• Fact finding and assessment• Review progress against audit plan• Revised activity• Final review/recommendations• Exit review with management/closing meeting• Report with time frame
The Inspection
38
Getting Started• Location• Contact• Time• Introductions• Walk-round• Company escort
The Inspection
39
Remember that an Inspection….
• Is a systematic approach• Involves interpersonal skills• Identifies deficiencies• Looks at what went wrong• Requires participation from both
parties
The Inspection
41
The Inspection
Asking Questions…..Open questions (that can not be answered by „yes” or
„no”) starting with:• What• Why• When• How• Where• WhoSilence can be very powerful – people find it
uncomfortable and try to say something
42
The Inspection
Good Listening – I• Stop talking! • Help the speaker to feel free to talk• Be approachable• Show the speaker that you are interested• Remove distractions• Try to understand the speaker’s point of
view
43
The Inspection
Good Listening – II• Be patient• Hold your temper• Try not to criticize• Ask questions• Stop, look and listen
44
The Inspection
How to Take Notes• Detail and facts — trust, but verify• Specifics not generalizations• Record detail as seen• Ensure accuracy• Be open
45
The Inspection
What to Record – I• Persons interviewed• Document numbers• Equipment numbers• Item identification
46
The Inspection
What to Record – II• Selection of document recipients• Condition of environment• Changes to facilities, equipment etc• Layout of area• Any obvious non-conformities
47
The Inspection
How to Record – I• Checklists• Flow-charts/process charts• Symbols such as a star (*) or a tick• Checks and follow-up
48
The Inspection
How to Record – II• Highlights• Short notes for the report
(reminders)• Tape recorder• Video camera• Camera
49
The Inspection
Checklists• Are structured• Detailed• Standard for all full inspections• Advantages
– Useful as reference– Good for training inspectors
• Disadvantages– Can lead to overlooking vulnerable areas of QA
50
The Inspection
Checklists –How to Use Them• Follow, but be prepared to be flexible• Use in preparation stage• Use to collect information and chart
progress• Preparation for the exit meeting• Preparation of the report
51
The Inspection
Aide-Mémoire• Simple, short list of actions and
aspects to be checked• Tailored for the inspection• Checklist and/or an aide-memoire
52
The Inspection
Taking Samples• Finished-released products• Raw materials • In-process materials• Inspector or sampler• Number of samples and sample size• Authorization
53
The Inspection
Objectives of Exit Meeting• Communicate observations• Inform management of findings• No surprises in report
54
The Inspection
Preparing for Exit Meeting – I• Group non-compliances• Categorise non-compliances
– Critical, major and minor
55
The Inspection
Preparing for Exit Meeting – II• Anticipate questions and discussion
or debate• In the case of a team of inspectors:
– Agree on a spokesperson– Agree on a note-taker
56
The Inspection
Exit Meeting Attendees• The inspectors• Senior management representative• Inspected managers and supervisors• Other interested parties
57
The Inspection
Running the Meeting – I• Inspectors must lead• Concise presentation• Discussion
– When to invite discussion and when to limit the discussion
• Mention good points before deficiencies
58
The Inspection
Running the Meeting – II• Treat challenges politely• Discuss and resolve conflicts• Admit if wrong• Don’t back down if convinced you are
right
59
The Inspection
Writing the Inspection Report• Each team member writes own part• Team leader has overall
responsibility• Signed by all team members• Approval from supervisor• To company within 4 weeks or less
60
The Inspection
Report Content• Part 1. General information on
company• Part 2. Description of the inspection• Part 3. Observations• Part 4. Conclusion and
recommendation• Annexes
61
The Inspection
Do Not Include• Subjective opinions• Irrelevant information• Ambiguous statements• Antagonistic statements
62
The Inspection
Style of Report• Use past tense• Keep it simple and based on fact• Include a summary
63
The Inspection
Report with Covering Letter to Company
• Any corrective actions to be taken• Time limits for implementing them• Confidential information• Exchange of reports• Regulatory measures if not
implemented
64
The InspectionRegulatory Measures
Depend on national legislation. Examples:
For new plants – No manufacturing licence/GMP certificate until compliance
For licence/certificate holders– Warnings– Fines– Suspension/withdrawal of marketing authorization for product(s)– Suspension/withdrawal of manufacturing licence/GMP certificate– Access to appeal
65
The InspectionCompany Strategies – I
Tricks RemediesTime-wasting Threaten to extend inspectionSide-tracking Stick to programmeProvocation Remain calmSamples provided Select your own sampleSpecial case Take notes and keep „never happened before” looking is there a trend?
Circular argument Recognize and stop
66
The InspectionCompany Strategies – II
Tricks RemediesTrial of strength Be firm; know your factsInsincerity Ignore itPity Sympathize; carry onAbsentees Call for deputyAmnesia Go back and get it
yourself
top related