Due Diligence Audits

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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 Internationa
l Safety Systems, Inc. (ISS), India
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AGENDA

• Pharmaceutical growth in India
• EHS status at Contract Manufacturing sites
• EHS audit objectives and methods
• Observations
• Outcomes
• Lessons Learned

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EVOLUTION OF INDIAN PHARMA INDUSTRY
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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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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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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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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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EHS Audits Conducted

• Germany
• Leverkusen
• Dessau-Wörlitz
• Ireland
• Arklow
• France
• Calais
• Spain
• Barcelona
• Ukrain
• Hungary (Budapest)

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EHS Audits Conducted

• USA
• Rancho Cordova, CA
• North Bend, LA
• Hickok, KS
• Canada
• Hamilton
• Brazil (two sites)

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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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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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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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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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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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General Safety and Controls

• Job Safety Analysis
• Permit Systems
• Fall Protection
• Machine Guarding
• Electrical safety and energy isolation procedures
• Housekeeping

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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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Life Safety and Emergency Response

• Means of egress
• Fire Protection Systems and Alarms
• Written Plans
• Evacuation Procedures

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Evaluation Criteria

• Parent company specific guidelines
• Local regulations
• National and international standards
• Best Practices in pharmaceutical industries

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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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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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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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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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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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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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Thank You Questions??