Due Diligence Audits At Pharmaceutical Contract Manufacturing Sites In India

1. www.issehs.com
International Safety Systems, Inc.
Due Diligence Audits at Pharmaceutical
contract Manufacturing Sites in India - Lessons
Learned
Prasanth.K, Deputy Project Manager, India
Pinky Bhatt, Project Manager, Asia-Pacific
International Safety Systems, Inc. (ISS), India

2. AGENDA
 Pharmaceutical growth in India
 EHS status at Contract Manufacturing
sites
 EHS audit objectives and methods
 Observations
 Outcomes
 Lessons Learned
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3. EVOLUTION OF INDIAN PHARMA INDUSTRY

4. India – Major focus for Contract
Manufacturing
According to a study in 2013, India is:
 4th in the world in terms of production volumes
 13th in domestic consumption
 Over 55% exports of India are to highly
regulated markets
 Largest exporter of formulations in terms of
volume with 14 % market share
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5. Contract Manufacturing Sites-
EHS Status
 Expert in manufacturing APIs and Formulations
 Limited EHS resources
– Competent professionals with competency in IH and
Process safety
– Understanding of IH significance especially for high
potent compounds
– Trained mentors such CIHs
 Willingness to learn and change
 Safety and environmental compliance is little
better – IH Process Safety needs significant
improvements
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6. EHS Audits
 Due Diligence audits for
– Potential suppliers
– With QA/QC Team
 EHS Assessments for
– Existing Suppliers
– API Manufacturing sites
– Formulation sites
– Vaccine plant
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7. EHS Audits Conducted
 India:
– Tarapur, Hyderabad, Goa, Mumbai,
Visakhapatanam, Ahmedabad,
Solapur, Cuddalore, Chennai,
Renukoot, more cities
 China (Two sites)
 Thailand (One site)
 Malaysia (One site)
 Indonesia (One site)
 Egypt (One site)
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8. EHS Audits Conducted
 Germany
– Leverkusen
– Dessau-Wörlitz
 Ireland
– Arklow
 France
– Calais
 Spain
– Barcelona
 Ukrain
 Hungary (Budapest)
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9. EHS Audits Conducted
 USA
– Rancho Cordova, CA
– North Bend, LA
– Hickok, KS
 Canada
– Hamilton
 Brazil (two sites)
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10. EHS Audit Objectives
 Evaluate compliance status with local health
safety and environmental regulations
 Evaluate site status with Pharmaceutical Supply
Chain Initiative,
http://pharmaceuticalsupplychain.org/
 Evaluate site status on generally accepted
industry practices for EHS
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11. EHS Elements Covered
 EHS organization and staffing, Employee EHS training
 Air Emissions, Wastewater Management, Waste
Management, Spill Prevention
 Hazard Assessment, Risk Assessment and Industrial
Hygiene Program
 Process Safety Management
 Emergency Response and Planning
 Personal Protective equipment -Written programs, Cleaning
and decontamination, Gowning de-gowning
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12. EHS organization and staffing
 EHS Staffing and Competencies
 Health, Safety, Environment Policy
 Safety committees
 Accidents reporting and investigation
 Training matrices and training conducted
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13. Air Emissions, Wastewater Management,
Waste Management, Spill Prevention
 License to operate
 Permits
 Pollution control
 Waste water treatment, Water discharge,
sampling, sludge solid handling
 Liquid and solid waste handling
 Used container, packing material handling and
disposal
 Hazardous waste handling and disposal
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14. Risk Assessment and Controls
 Hazard Communication, Chemical Inventory,
Labeling, MSDS
 Risk Assessment procedures, Follow up
 Qualitative and quantitative exposure assessment
 Potent compound handling /Particulate
containment
 Hierarchy of exposure control measures and
validation
 Equipment and personnel entry and exit
 Local Exhaust Ventilation and Preventive
Maintenance
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15. General Safety and Controls
 Job Safety Analysis
 Permit Systems
 Fall Protection
 Machine Guarding
 Electrical safety and energy isolation procedures
 Housekeeping
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16. Process Safety
 Storage, handling and transportation of
flammable and reactive chemicals
 Storage tanks
 Pressure vessels
 Safety valves
 Control of ignition sources (e.g., static
electricity) in flammable area
 Inerting, validation of inerting
 Compressed gases, boiler and pressure vessels
controls
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17. Life Safety and Emergency
Response
 Means of egress
 Fire Protection Systems and Alarms
 Written Plans
 Evacuation Procedures
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18. Evaluation Criteria
 Parent company specific guidelines
 Local regulations
 National and international standards
 Best Practices in pharmaceutical industries
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19. Audit Process followed
 Planning
– EHS Questionnaire
 Site visit (3 to 5 days)
– Opening meeting /introduction
– Walkthrough
– Detailed site visit
– Stake-holders meeting (maintenance, Engineering,
Physician)
– Documents review
– Closing conference
Draft and final report
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20. Most Common Observations-
Environment
 Regulatory
– Environment Consent Requirements (quantity
of waste generated, disposed off)
 Non-regulatory
– Determining presence of API in Waste
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21. Most Common Observations-
Process safety and personal
safety
 Process Safety
– Nitrogen inerting not done at all or not validated
– Grounding/Bonding and static electricity control
measures
– Flammable tank/container storage (Dike capacity,
flame arrestor)
 Personal Safety
– Energy Isolation procedures
– Fall Protection
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22. Most Common Observations-
Industrial Hygiene
 Qualitative Exposure Assessment
 Reliable, reproducible and representative
quantitative exposure assessment for APIs and
solvent
 Hierarchy of Controls (RPE reliance)
 Robust RPE program
 Gowning de-gowning, airlock rooms
 Potential contamination of Green Zones
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23. Outcome
 Sites receptive and supportive
 Some of the observations addressed immediately
 After audits, QLEA and QNEA were conducted with
reliable methods
 Containment validation conducted as required from
parent company
 Significant increase in awareness for IH and Process
Safety
 Basic training conducted
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24. Lessons Learned
 Auditing – especially based on site visit to
determine effectiveness of compliance – is
powerful tool in ensuring EHS compliance status
and reducing EHS risk
 Spend more at site at every corner and less in
looking at records
 Closing meeting – to receive feedback before
report goes out is critical
 Stay away from commenting audit conclusions
such as “show stoppers” until all aspects are
considered
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25. Thank You
Questions??
25