audit - inspection - eudipharm · pharmacovigilance audit/inspection as an example conclusion . 3...
TRANSCRIPT
1 Rabia BERTHIER-MARSOU
AUDIT - INSPECTION
EUDIPHARM
5th December 2011
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Plan
What is an audit / inspection ?
What is the audit objective ?
What is the inspection objective ?
List of Main Pharmaceutical Regulatory References
Audit / Inspection Main steps
Audit/Inspection Approach
Whose Audit/Inspection is This?
How to prepare the audit / inspection ?
What happen during audit/inspection?
Support During the Inspection
Code of conduct
Pharmacovigilance audit/inspection as an example
Conclusion
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What is an audit / inspection ?
Definition AUDIT "comes from the Latin "AUDIRE" which means TO LISTEN (not to be
confused with to hear). "A METHODICAL, INDEPENDENT and DOCUMENTED process enabling to obtain proofs of Audit and to assess them objectively in order to determine whether the Audit criteria are followed" ISO 9000
Type audit / inspection Internal audit: audit performed by the company auditor (or outsourced)
External audit: audit performed by external auditors (e.g. partner’s audits)
Inspection: audit from Competent Authorities
=> Routine, For Cause, Due Diligence
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What is the audit objective ?
Internal Audit aims to Have beneficial results for the company (e.g. streamline the processes)
Asses non-compliance with the regulation and the company requirements
Identify opportunities of continuous improvement (process, documentation, organization …)
The deliverable is always an action plan including a detailed evaluation of deadlines and responsibilities established in a report in order to limit objective risks, with the best possible return on investment
External Audit aims to: Check non-compliance with the contractual agreements between the
company’s auditors and the audited company
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What is the inspection objective ?
Inspection aims to establish if the inspected company: Is compliant with relevant EU regulations
Has appropriate staff. They will review individual’s training folders, Interview individuals on their roles and job-related responsibilities
Has defined, documented procedures that are followed and effective
Has validated and controlled equipment
Has process checks (QC) within key processes with corrective actions, if needed
Has Clear documentation and audit trails
Has Data security and subject protection
Undergone and will continue to have regular checks from the Company’s Quality Assurance function.
=> To protect the patient
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List of Main Pharmaceutical References (1/2)
Audit
Regulation 1235/2010
Directive 2010/84/EC
V9a
Good Manufacturing practices (§9)
Good Clinical Practices (ICH E6)
Good Distribution Practices (chap 8)
ISO 9001 (§8.2.2)
ISO 19011: Guidelines for auditing the quality and/or
environmental management systems
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List of Main Pharmaceutical References (2/2)
Inspection
Regulation 1235/2010
Directive 2010/84/EC
V9a
Good Clinical Practices (ICH E6)
Volume IV (GMP)
GDP
Etc.
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Audit/Inspection Main Steps (1/2)
PREPARATION
CONDUCT
FORMALIZATION
Letter of notification:
-Subject,
-Date, time, duration,
-Location,
-Language,
-Scope,
-Audit team,
-Programme
FOLLOW-UP
-Opening meeting
-Audit/inspection in a
room (interviews)
-Audit/inspection in the
field (demonstration)
-Preparing the closing
meeting
-Closing meeting
Final report Reception
(Findings)
Answer the Final report
(CAPA)
CAPA Follow up
Reporting to top
management (Escalation
process)
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Audit/Inspection Main Steps (2/2)
Opening meeting:
Mutual agreement on objectives and scope
Verification that the proposed plan is feasible and adjustable if needed.
The auditor/inspector confirms the date, time, and place to make sure that the participants will be available for the closing meeting
Closing meeting:
Open a discussion between all participants
Make sure that everybody understands each point..
Agree on the findings stated by the auditors/inspectors
Ask for the date limit for issuing the report
Confirm the method and the time limit to fix the findings
Confirm whether there will be a follow-up audit/inspection .
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Audit/Inspection Approach
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3
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Whose Audit/Inspection is This?
Mainly focus on the announced scope and the functions that interact with audited/inspected department
BUT
The audit/Inspection may have impact on more extended area
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How to prepare an audit/inspection – Before (1/4)
Define the audit/inspection team leader Responsible for the coordinate the whole audit/inspection (from the
preparation to the CAPA follow up)
Communicate to all concerned staff (sites, corporate, business partners) Scope and context, Date, duration, number of auditors/inspectors, Agenda, etc.
Identify interviewed people (based on the agenda)
Organise mock interviews Answer auditors/inspectors questions if any
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How to prepare an audit/inspection – Before (2/4)
Identify area for improvement
Establish an action plan to improve the weakness
Review your procedures related to the audited/inspected area
Ensure CAPA from previous audit/inspection closed and proofs available
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How to prepare an audit/inspection – Before (3/4)
Set up an efficient organisation Book the back-room
- Choose a room that is not on the same floor as the offices of the interviewees
Book the auditors/inspectors room - Choose a room that is not on the same floor as the back-room
Identify - the runner - the scribe - Escort - Leader(s) of the back-room
Prepare the necessary materials for the back-room and the auditors/inspectors room - Computer for demonstration - Computer for the scribe and the back-room - Chocolate, drinks, etc.
Book “plateaux repas“ for the interviews and auditors/inspectors Predefine a process to handle auditors/inspectors requests during the audit/inspection
- Tracking, validation, transmission, etc.
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How to prepare an audit/inspection – Before (4/4)
Ensure personal training folders are up to date Current job description
Current CV
Training records that document completed training
Ensure interviewees will clean their desk
Etc.
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What happen during audit/inspection ?
Auditors/Inspectors appear at reception – sign-in
Receptionist calls nominated site ‘Host’ and informs him of the auditors/inspectors arrival .
Host notifies relevant people in site and corporate management
Auditors/Inspectors are escorted to a pre-booked room where the audit/inspection take place (opening meeting, interviews, documentation review, etc.)
Possible Inspection Activities Documentation review (SOPs, reports, training…)
View demonstrations (e.g. data entry)
Interview individuals
Facility audit/inspection (they may request to visit work areas, archives..)
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Support During the audit/Inspection (1/2)
back-room’ and pre-defined processes for handling requests from the auditors/inspectors At least 1 permanent person to coordinate the back-room 1 person to track requests Process owner ad hoc (to validate the requested documents)
Validation of the documents before going to the inspector: 1st validation by the process owner 2nd validation by QA
Interviewee’s office where auditors/inspectors located Scribe + interviewed people Scribe => to track and send all questions to back room Runner (Link between backroom and interviewee’s office to give the validated
documents) Interview
The interviewees should be briefed in the back-room before the interview
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Support During the audit/Inspection (2/2)
Example INTERVIEWEE’S OFFICE
QA
Scribe,
Etc.
Interviewee(s) Auditors/Inspectors
Attendees
BACK ROOM
Validated
Answers
Q
Other Depts
/sites/
etc.
Coordination:
- Ensure the tracking of requests
- Ensure that all requests have been answered
Validation:
- Process owner: 1st validation
- QA: Final Validation
Q
A
Escort: Follow auditors/inspectors
on all displacements
Organisation can be specific
depending on the
audit/inspection scope
However
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Code of conduct - Do’s (1/6)
Remain professional
Obtain a clear understanding of what the question is before answering - ask for clarification
Give direct, honest answers to questions, but use caution against answering questions that are unclear
You can take notes of the question the auditor/inspector asks if that helps you
Put your mobile on silent!
A positive attitude projects confidence and control
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Code of conduct - Dont’s (2/6)
Don’t ask if you can tape the interview
Don't guess an answer to a question - Just say you don't know or that you need to consult an SOP or your manager etc.
Don’t answer for someone else (e.g. if you are from supply and the auditor/inspector’s ask a QA question, state that this question would be best answered by your QA representative)
Don't offer information without specifically being asked- Stop talking when you have answered the question
Don't sign anything
Don’t provide any documentation requested by the auditors/Inspector’s that has not been validated by the designated member of the audit/inspection Team
Don't ask for advice during an audit/inspection
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Code of conduct – Your role (3/6)
Conduct business as usual
Be prepared for expected and unexpected interview
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Code of conduct - Common Auditor/Inspector Interview Techniques (4/6)
Silence after you have given information It's OK to have silence / You don't have to talk
Wait for their next question or ask if you have answered their question
Turn your response into a question with implied doubt Don’t be unnerved
Don't volunteer information
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Code of conduct - Common Auditor/Inspector Interview Techniques (5/6)
Ask questions about another area or job Speak only for your own role
Don't talk about someone else's job
Ask broad, open ended questions Be sure you have enough information to provide an answer
Ask them to be more specific
Be factual
Do not answer hypothetical questions
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Code of conduct - Maintaining Your Office Environment (6/6)
Have a Clear desk policy
Remove sticky notes, out of date charts from the department
Remove archiving, check up to date
Promptly collect printouts from faxes and printers
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PV audit/Inspection as an example
EUDIPHARM
5th December 2011
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Preparation and Conduct
Report & Answers Preparation
First Contact
D0 D1 to D5 8 weeks
Request for Opening Closing Feedback Documents meeting meeting on answers report Notification: Company
answers
6 weeks
Conduct
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Preparation
Review of the documents requested from the company:
Organisation chart
CV/function for PV and EU QP PV
Drug product portfolio (CP, MRP, NP)
List of latest submitted PSUR for each product (submission date–period covered) + submission schedule + process)
ADR/AE processing flowchart for PV and CTs
Compliance metrics (cases, PSUR/ASR)
Quality Management System description: QA, SOPs, QC, CAPA, audit …
Contracts/agreements incl. subcontracted PV activities
Databases: history, scope, OS, software, validation process
Copies of main SOPs related to PV activities
List of SOPs concerning product quality complaints and medical information – interfaces
List of post-marketing authorisation studies (PAS)
List of SAE including SUSAR for PAS (clinical trials)
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Conduct
Opening meeting: regulatory frame, agenda
Company presentation : organisation, activities, portfolio, partnership, subcontracted activities…
PV organisation
Staff: functions, training and qualification
Pharmacovigilance and safety data in CTs/studies:
collection, processing and reporting of spontaneous cases (incl. cases from observational studies and literature cases), CTs cases pregnancy/lactation cases, specific populations follow up (pediatric..)
Medical and scientific literature screening
Cases review
PSURs and DSUR preparation and submission
Safety profile continuous evaluation / signal detection
Management of responses to questions from CA related to product safety
Risk management plans: system in place and animation
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Conduct
Activities having an impact on PV activities/ management of safety data from CTs and studies:
Interfaces with - Product quality complain
- Medical information
- Legal (contracts, cases)
- Clinical trials
- Marketing
Management of reference document/ RA interface : SPC, CCDS and IB
PV database: history (incl. data migration), change control, backup/restoration/business continuity plan, security aspects, maintenance, administration, validation process, …
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Conduct
Contracts, subcontracts and other partnerships
PV Scope
Quality Management System
Organisation
Audit
SOP and related documents (incl. archiving)
QC/Indicators (quality and delay)
Closing meeting: Listing of findings announced
Deviations (regulations)
or remarks (guidance)
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Conclusion
Take Audits/inspections seriously every audit/inspection, wherever it is, is an audit/inspection of your
company
they can have far-reaching impact
Inspection Worst possible scenario for the Company is: Fine / Imprisonment
Both of the above
Company Closure(?)
Also have warnings, naming, formal caution, urgent product safety review and restrictions, Market Authorisation withdrawal or product suspension