audit - inspection - eudipharm · pharmacovigilance audit/inspection as an example conclusion . 3...

1 Rabia BERTHIER-MARSOU

AUDIT - INSPECTION

EUDIPHARM

5th December 2011

2

Rabia BERTHIER-MARSOU

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

3


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

1

2

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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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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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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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

25 Rabia BERTHIER-MARSOU

PV audit/Inspection as an example

EUDIPHARM

5th December 2011

26


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