How To Face Overseas Audits

HOW TO FACE OVERSEAS AUDITS
S.M. MUDDA
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WHY AUDITS ?
MANUFACTURERS PERSPECTIVE Facing overseas audits and getting the regulatory approval of the importing country is the first requirement any manufacturer, intending to export drugs has to fulfill.
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WHY AUDITS ? REGULATORY PERSPECTIVE Minimizing risks to the health of the consumers in the country importing the drugs is the mandatory responsibility of the regulatory agencies

WHY AUDITS ? REGULATORY PERSPECTIVE The guiding philosophy of the regulators for accepting the drugs for import is based on the assumption that drugs not produced under GMP conditions are deemed to be adulterated.
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WHY AUDITS ? Purpose of the audit therefore is to confirm that adulterated drugs are not allowed to be imported. This is done by verifying that the drugs are manufactured in accordance with the GMP guidelines/requirements of the importing country
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REGULATORY REQUIREMENTS Therefore it is essential for the companies to know the regulations of the importing countries as applicable to their products. The developed countries have their own guidelines .e.g.: EU guidelines to Good Manufacturing Practice (Medicinal Products for Human and Veterinary use) October 2005

REGULATORY REQUIREMENTS 21 CFR Part 211, Current Good Manufacturing Practice for Finished Pharmaceuticals However, the good news is that there has been an attempt of harmonization of the cGMP regulations world wide.
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REGULATORY REQUIREMENTS US FDA under its Pharmaceutical CGMPs for the 21st Century initiative saw the need to harmonize CGMPS with the globally followed Quality Systems. As a result of this initiative, FDA has issued a guidance for the industry Quality Systems Approach to Pharmaceutical CGMP Regulations
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REGULATORY REQUIREMENTS Guidelines of quite a few countries are similar in terms of their expectations for GMP compliance . While the rest of the world countries have their own guidelines, most of the countries follow WHO GMP guidelines for carrying out the audits.
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PREPARATION FOR THE AUDITS The first requirement is to have a Management Team working under a welldefined organization chart The individual identified to lead the inspection is usually the Head of QA and the other key members are: Head of Production Head of Quality Control
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PREPARATION FOR THE AUDITS Head of Engineering Services Head of Formulation Development Head of Regulatory Affairs Secondly, it should be ensured that the Manufacturing Facility is GMP-compliant
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PREPARATION FOR THE AUDITS The basic documents which are required to be kept ready before the audit are: A Site Master File (PIC/S,WHO requirements) Quality Manual Other documents of level 2,3 and 4 of the documentation system
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PREPARATION FOR THE AUDITS Documentation for Quality System Level 1:Quality Manual Level 2:Quality Assurance Procedures Level 3:Work Instructions (SOPs) Level4: Forms and Records
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QUALITY MANUAL
Quality Assurance Procedures Validation Master Plan (Quality System Procedures) Site Master File
Qualification Protocols & Reports
Validation Protocols & Reports
Master Documents
Operating Procedures
Master Formula Record
Batch Manufacturing & Packing Record
Specification & Test Procedures
Stores Procedures
Production Procedures
Quality Control Procedures
Maintenance Procedures
Human Resources Procedures
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Classification of Quality System Procedures

QAP : 001 QAP : 005 QAP : 006 QAP : 007 QAP : 008 QAP : 026 QAP : 031 Management Organization Training of Personnel
QAP : 002 QAP : 003 QAP : 021 QAP : 044 QAP : 004
Procedure for Launch of New Products
Product Design and Technology Transfer Creation and Approval of Artworks Stability Studies of Drug Products
Product Development for Regulated Market

Quality Policy
Change Control
Design & Control of Documents Design of Master Documents Design of Validation Documents Preparation of Site Master File
QAP : 034 Handling of Materials for Product Development QAP : 035 QAP : 036 QAP : 037 Process Validation Cleaning Validation Validation of Analytical Method
Management Organization
QAP : 009 QAP : 010 QAP : 054 QAP : 011
Item Codification System Vendor Approval Indent and Purchase of Raw and Packing Material Receipt, Storage & Handling of Raw & Packing Materials
Product Design & Development
Document Design & Development
QAP : 053 Preparation & Submission of Technical Dossier for Regulated Markets
QAP : 018 QAP : 025 QAP : 040 QAP : 041
QAP : 032 QAP : 033
Facility / Equipment QUalifcation

QAP : 051
Maintenance of Equipment Calibration Qualification of Equipment Handling of Service Contracts

Self - Inspection Product Quality Review
Production Planning and Control Export Order Review
Materials Control
QAP : 012
QAP : 038 Post Approval Manufacture of Commercial Scale Batches
Production & Process Control
QAP : 013 QAP : 014 QAP : 015 QAP : 017 Products

QAP : 023
Creation and Completion of BMR & BPR Manufacturing of Bulk Product Packing of Bulk Product Receipt, Storage and Handling of Finished
Quality Control
QAO : 016 QAP : 019 QAP : 042 QAP : 027 QAP : 039 QAP : 028 QAP : 029 QAP : 030 QAP : 020 Handling of Deviations Control of Non-Conforming Products Incident Reporting and Investigation Handling of Out of Specification (OOS) Test Results Product Recovery Handling of Market Complaints Handling of Adverse Drug Reaction Complaints Product Recall Handling of Returned Products
Quality Control of Raw & Packing Material Quality Control of Bulk & Finished Products
Self Inspection
QAP : 024
QAP : 045 Handling of Stability Samples for Domestic Market & Reporting Results of Analysis QAP : 052 Handling of Laboratory Materials Testing of Samples & Reporting of Results of QAP : 022 Analysis
Handling of Discrepancies
CAPA
QAP : 0043
Corrective and Preventive Action (CAPA)
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PREPARATION FOR THE AUDITS Trained Manpower Operators: For performing the jobs in accordance with written instructions Middle Level Managers:To implement the Companys System Procedures Top level Managers: To design documents consistent with the regulatory requirements
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PREPARATION FOR THE AUDITS Conduct mock audits and resolve the deficiencies Select a conference room as the meeting place Prior to the inspection bring or have ready to bring all pertinent documentation
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PREPARATION FOR THE AUDITS Do a rehearsal with role playing Ask yourselves problem questions Identify and clearly archive all GMP/non-GMP documentation
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SCOPE OF THE AUDIT Opening Meeting Company Presentation Production Facility Tour Utility Visit On-line Documentation Review
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SCOPE OF THE AUDIT Quality Review System Documentation
Closing Meeting Audit Report

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SCOPE OF THE AUDIT
Basic observations during the facility tour are aimed at finding out: Whether the products are being manufactured in a Qualified Facility (Qualified Building, Qualified Production Equipment, Qualified Utilities) using Validated Processes to ensure that products of required quality are manufactured consistently. 21

SCOPE OF THE AUDIT Basic observations during the facility tour are aimed at finding out: Possibility of mix-ups of the materials during storage and handling and products during manufacture and handling Possibility of Cross-Contamination (Important in multi-product facilities)
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SCOPE OF THE AUDIT Areas of focus during the tour: Personnel and Materials Flow Auditors normally follow the flow of materials and product- in- process. Some start with an external round of the site Whether entry procedures and gowning practices are adequate
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? Whether the Facility finishes are state-of-the art Facility Housekeeping/Sanitation is of high standards Housekeeping equipment is separately stored and cleaned 24

SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? Whether the men and material entries are well protected from external contamination and Pest Control is in place Receiving and dispatch bays are provided
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? Are all components, raw materials, etc. properly identified? Status Labelling of the Stored Materials Area in Use, Equipment In Use, Materials in Process , Bulk Product , Packed Product is correct?
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? Access control for restricted areas are provided Secured storage of raw materials, printed packing materials, intermediate product and finished product is ensured
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? Do the instruments and equipment look clean and labelled and stored properly? Calibration Status of Measuring Devices is indicated on the equipment Daily check on Weighing Balances is performed
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? Standard calibrated weights traceable to national standards are used Is there a preventive maintenance program for: All processing and packing equipment All utilities
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? Whether maintenance records are available Environmental Conditions are appropriate to the activities carried out Environmental Conditions are monitored and recorded
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? All Activities are carried out in accordance with the authorized written instructions Batch records used are verified and approved by QA to confirm that they are based on the current approved versions of the Master Formula Records
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? On-line recording of the activities performed is done in the Batch Manufacturing Record (BMR) and signed and dated by the operator and the supervisor Is data in the BMR adequate to demonstrate compliance with the GMP requirements.
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? Cursory data in the BMR and reference to many additional records/logs is not appreciated Deviations from the instructions are reported and investigated Non-standard batch sizes are not accepted
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? Receipt and verification of all materials and product- in-process is done and recorded All in-process controls are performed and recorded in the BMR
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SCOPE OF THE AUDIT Areas of focus during the tour: What is looked at? In Quality Control Laboratory reliability of the data is verified: All instruments are calibrated Volumetric solutions are prepared and used correctly Current specifications and work records are used for analyzing the samples 35

SCOPE OF THE AUDIT Review of documents Current Authorized Versions of Documents are under use Do the SOPs describe what is to be done? Do you follow what the SOPs describe? Are the SOPs clear and precise? Are the SOPs available to all manufacturing and support personnel?
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SCOPE OF THE AUDIT Review of documents Have the personnel been trained on the pertinent SOPs? Are the training records up-to-date Area and equipment usage logs are maintained at the place of use Environmental monitoring logs are available
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SCOPE OF THE AUDIT Review of documents Quality System Documents dealing with the following are checked: Deviations Change control Non-Conforming Product Market Complaints Product Recall
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SCOPE OF THE AUDIT Review of documents Quality System Documents dealing with the following are checked: Incident Reporting CAPA (Corrective and Preventive Actions)
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INTERACTION WITH THE INSPECTORS Business-like, Normal ( not under pressure, not too friendly), Polite Check and confirm correct name, pronunciation of the name, how he/she would like to be addressed Avoid first names. Form of address as Mr. or Ms. before the surname / family name
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INTERACTION WITH THE INSPECTORS Do not stand behind the auditor .Do not see over his/her shoulder Do not talk / chat with others during the audit One nominated person should accompany and deal with the inspector who should be either the Head of Q A or the unit head but not certainly any administrative /marketing 41 executive

HOW TO ANSWER THE QUESTIONS ? Understand the question and ask politely to repeat the question, if not followed Do not panic ! Be honest Answer the question Do not volunteer information
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HOW TO ANSWER THE QUESTIONS ? Identify the problem clearly Was anything done earlier What can be done now What is to be done in the near future What can be done to prevent a recurrence Try not to react to the situation with a immediate corrective action
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HOW TO ANSWER THE QUESTIONS ? Identify confidential documents Make two copies of every document that is requested and retain one copy Take good notes of the observations made / discussions held Ensure that the context of the observations is clearly understood and explained
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HOW TO ANSWER THE QUESTIONS ? What arouses suspicion? Batch production records look neat Evasive or nebulous answers Several SOPs revised on same date Confusion among employees
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HOW TO ANSWER THE QUESTIONS ? What arouses suspicion? Not clear on dates started or stopped for production Hold times not justified Eye contact or body language
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POST AUDIT ACTIONS During the exit meeting Assemble a pertinent team Listen Take notes Ask questions Clarify observations Discuss If corrected state as such
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POST AUDIT ACTIONS Do not make commitments that can not be kept Agree to reasonable timelines Management can challenge observations Provide supporting documentation
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POST AUDIT ACTIONS Reconvene to discuss observations Prepare response to deficiencies Address promised/agreed to corrective actions Prepare strategies to close out inspection Communicate with agency Communicate proactively!
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DOS AND DONTS DOS: Follow the instructions given in this presentation Be Sincere Show keenness in responding Accept suggestions Honestly accept if something is not done
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DOS AND DONTS DONTS: Never argue Never engage in discussion on unrelated matters during the audit Do not try to cover up Do not show- off Do not justify any point by being defensive
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HOW TO FACE OVERSEAS AUDITS A final word:

Do not consider audits as a burden but an opportunity to learn and improve Be proud to show your facility, documentation and demonstrate your commitment to CGMP Be positive and enjoy the experience If you follow this approach the approval of your facility is in your hands
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THANK YOU FOR YOUR ATTENTION
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How To Face Overseas Audits

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