1. www.issehs.com Developing Sustainable EHS Programs at Pharmaceutical Companies in Emerging Economies – India Experience Maharshi Mehta, CSP, CIH Toral Mehta, CIH International Safety Systems, Inc USA-India-China-Mexico-Brazilwww.issehs.com 1-1 Pharma Forum, 2010 AIHCE, Denver, May 26, 2010

2. www.issehs.com Agenda Part 1: Part 1: –Introduction and background –Challenges in EHS –Approaches Adopted –Institutions –Regulatory Framework Part 2: Part 2: –Case Studies –Supply Chain Site –Pharma Corporation with manufacturing site –Third Party Contract Manufacturers (TCM) 2

3. www.issehs.com Basis for Presentation EHS capacity building in pharma companies in Emerging Economies EHS capacity building in pharma companies in Emerging Economies Lessons learned from: Lessons learned from: –Conducting IH Process Safety Assessments at Pharma companies, supply chain and contract manufacturing sites –Conducting > 5000 API Surrogate monitoring –Assisting in exposure control and program implementation –Developing Pharma Company specific training modules and conducting training for companies and Third Party Manufacturers (TPM). –Most importantly, from Corporate EHS leaders and EHS work conducted globally 3

4. www.issehs.com Introduction India ranks third in terms of manufacturing pharma products by volume India ranks third in terms of manufacturing pharma products by volume World’s largest producer of bulk drugs World’s largest producer of bulk drugs Worth $13B market Worth $13B market ~ 10% annual growth ~ 10% annual growth Supply chain, third party manufacturing increasing rapidly Supply chain, third party manufacturing increasing rapidly Outsourcing expected to exceed $53B in 2010 Outsourcing expected to exceed $53B in 2010 Share of generic in US from Indian companies expected to grow at 6% in 2011 from 2% in 2006 Share of generic in US from Indian companies expected to grow at 6% in 2011 from 2% in 2006 http://www.slideshare.net/workosaur/indian-pharma-industry-presentation- 010709?from=share_email 4

5. www.issehs.com Clusters of Pharma Companies 5 Ahmedabad, Baroda, Ankleshwar Hyderabad Baddi, Chandigarh Mumbai, Aurngabad Nasik Goa

6. www.issehs.com Infrastructure Over 450 colleges/departments offering degree and other education programs in pharmaceutical science Over 450 colleges/departments offering degree and other education programs in pharmaceutical science More than 50,000 students graduates/year More than 50,000 students graduates/year Manufacturing equipment, containment technologies Manufacturing equipment, containment technologies R&D centers, laboratories R&D centers, laboratories Two colleges offering Master in Industrial Hygiene Program Two colleges offering Master in Industrial Hygiene Program 150 Industrial Hygienists for all companies 150 Industrial Hygienists for all companies 5 CIHs 5 CIHs Safety professionals or occupational physicians practicing IH Safety professionals or occupational physicians practicing IH No Accredited Lab for API/Surrogate No Accredited Lab for API/Surrogate 6 Pharma ManufacturingEHS

7. www.issehs.com Challenges Limited Resources – IH professionals Limited Resources – IH professionals QA in exposure assessment data QA in exposure assessment data Financial constrains Financial constrains –Price Controls –Competition Manufacturing and outsourcing is increasing rapidly and corporate EHS and other resources are decreasing Manufacturing and outsourcing is increasing rapidly and corporate EHS and other resources are decreasing Trained corporate EHS professionals are unable to cop- up with demand for assistance Trained corporate EHS professionals are unable to cop- up with demand for assistance Distance, time difference Distance, time difference Limited sensitivity of site professionals to potent compounds Limited sensitivity of site professionals to potent compounds 7

8. www.issehs.com Approaches: Corporate and Regional EHS Commendable efforts Commendable efforts Audits Audits Regional training programs and meetings Regional training programs and meetings Strong contract manufacturing programs Strong contract manufacturing programs Emphasis on selection of credible, competent and cost-effective EHS service providers Emphasis on selection of credible, competent and cost-effective EHS service providers Providing limited financial support Providing limited financial support 8

9. www.issehs.com Approaches Education Programs in Industrial Hygiene Education Programs in Industrial Hygiene –University Level –Pharma specific training modules Managing cost effectively Managing cost effectively –Cost effective consulting –Exposure assessment strategy – three samples /HEG/API, never 1 sample –Analytical cost discounts –Return on investment (e.g., savings from loss of API) –Not loosing focus on QA 9

10. www.issehs.com Approaches Empowering region and manufacturing sites in EHS Empowering region and manufacturing sites in EHS Training Training –At the foundation of sustainable EHS program –Site specific, anecdotal, workshop at the site –One corporation spends closed to $1B in all training Qualitative Risk assessment and Control Banding Qualitative Risk assessment and Control Banding –If exposure is obvious, why do monitoring? –Exposure control and then monitoring Surrogate Monitoring Surrogate Monitoring 7/24 support 7/24 support 10

11. www.issehs.com Approaches – Supply Chain Corporate requirement for supplier to demonstrate exposure is below OEL through surrogate monitoring Corporate requirement for supplier to demonstrate exposure is below OEL through surrogate monitoring Corporate Audit Corporate Audit Local services provider to do hand-holding for some time Local services provider to do hand-holding for some time –On site training on process safety and IH –Limited exposure assessment –Periodic supervision –7/24 support Limit number of suppliers based on EHS performance Limit number of suppliers based on EHS performance Shutting down operation when risk is imminent- provide limited assistance in reducing risk Shutting down operation when risk is imminent- provide limited assistance in reducing risk 11

12. www.issehs.com Case Study 1 Third Party Manufacturer (TPM) 12

13. www.issehs.com Case Study 1: Background Supplier of Bulk drug to Pharma Corporation Supplier of Bulk drug to Pharma Corporation Formaldehyde and other solvents used Formaldehyde and other solvents used Open vessels, no inerting, high process safety risk Open vessels, no inerting, high process safety risk Open formaldehyde handling Open formaldehyde handling Compressed air used for barrel transfer of chemicals Compressed air used for barrel transfer of chemicals EHS expertise not available at site EHS expertise not available at site Local workforce with limited knowledge on process safety and occupational hygiene Local workforce with limited knowledge on process safety and occupational hygiene 13

14. Case Study 1: Approaches Adopted Corporate EHS professional conducted on- site review Corporate EHS professional conducted on- site review Shut down the operation with high process safety and health risk Shut down the operation with high process safety and health risk TPM contacted us TPM contacted us Detailed review and exposure assessment conducted, provided process and exposure controls Detailed review and exposure assessment conducted, provided process and exposure controls –Enclosed vessel –Inerting specifications –Grounding bonding, intrinsically safe lighting –LEV, PAPRs Re-evaluation of TPM site and facility started within 3 months with significantly reduced risk Re-evaluation of TPM site and facility started within 3 months with significantly reduced risk 14

15. www.issehs.com Case Study 1: Training In consultation with Corporate EHS staff conducted training for all suppliers and TPMs In consultation with Corporate EHS staff conducted training for all suppliers and TPMs Risk specific manual developed Risk specific manual developed Conducted 3-day workshop on basics of process safety, personal safety and industrial hygiene for all CMs and suppliers Conducted 3-day workshop on basics of process safety, personal safety and industrial hygiene for all CMs and suppliers About 40 professionals from all TPM sites attended About 40 professionals from all TPM sites attended Ongoing support to TPMs Ongoing support to TPMs 15

16. www.issehs.com Case Study 2 Corporation with Manufacturing in India 16

17. www.issehs.com Case Study 2: Background High potent compound formulations High potent compound formulations Effective containment for the most part Effective containment for the most part Limited Training Limited Training Previous exposure monitoring not conducted Previous exposure monitoring not conducted Half face APR or mask used Half face APR or mask used 17

18. Case Study 2: Approaches Adopted Detailed Qualitative Exposure Assessment Detailed Qualitative Exposure Assessment Base line – limited Quantitative exposure assessment Base line – limited Quantitative exposure assessment Exposures identified Exposures identified 7/24 support 7/24 support Participation in monthly meeting Participation in monthly meeting Recommendations: Recommendations: –Improve containment efficiencies –Work with equipment supplier –Additional exposure controls, e.g., LEV for compression machine part cleaning –PAPRs in place of APRs –Employee work practices 18

19. www.issehs.com Case Study 2: Approaches Exposure Assessment Exposure Assessment –CIH and IH conducted periodical exposure assessments to identify continual improvements –More than 400 API samples collected over a period of 4 years to identify continual improvements –American Industrial Hygiene Association (AIHA) accredited laboratory in the USA analyzed samples –The facility demonstrated continual improvements Training Training –Developed training manual with seven chapters – Specific for APIs used and risk identified –Corporate EHS reviewed manual and provided input –Conducted on site training with workshops 19

20. www.issehs.com Case Study 3 Domestic Pharmaceutical Company 20

21. www.issehs.com Case Study 3: Background Supplier is one of the largest drug manufacturers Supplier is one of the largest drug manufacturers Pharma Corporation selected the supplier Pharma Corporation selected the supplier Also, required the supplier to conduct surrogate monitoring and demonstrate that exposure will be controlled when their drugs are made Also, required the supplier to conduct surrogate monitoring and demonstrate that exposure will be controlled when their drugs are made Objectives Objectives –Containment validation –Identify cross contamination –FDA risk assessment 21

22. www.issehs.com Case Study 3: Approaches Adopted Surrogate monitoring Surrogate monitoring –ISPE protocol followed –Site specific protocol developed –Lactose used –More than 350 air and swab samples collected –Containment validation and cross contamination studies performed simultaneously Recommendations: Recommendations: –Improved containment –Engineering controls (LEV) 22

23. www.issehs.com Organizations and Institutions Organizations of Pharmaceutical Producers of India (OPPI) Organizations of Pharmaceutical Producers of India (OPPI) –http://www.indiaoppi.com/ –Key collaborator in EHS –We have offered two Workshops on Industrial Hygiene and Safety Indian Pharmaceutical Manufacturers Association Indian Pharmaceutical Manufacturers Association National Institute of Pharmaceutical Education and Research in India (4 locations) National Institute of Pharmaceutical Education and Research in India (4 locations) National Pharmaceutical Pricing Authority fixing and controlling prices of drugs National Pharmaceutical Pricing Authority fixing and controlling prices of drugs 23

24. www.issehs.com Health and Safety Regulations Director General Factory Advise and Service Labor Institute (equivalent of NIOSH, HSE) Director General Factory Advise and Service Labor Institute (equivalent of NIOSH, HSE) –http://dgfasli.nic.in/welcome.html Indian Factories Act 1948 and subsequent amendments Indian Factories Act 1948 and subsequent amendments –http://dgfasli.nic.in/statutes5.htm http://dgfasli.nic.in/statutes5.htm –Schedule 2 on Permissible exposure limits State Rules State Rules Drugs and Pharmaceutical Industries covered under List of Industries Involving Hazardous Processes Drugs and Pharmaceutical Industries covered under List of Industries Involving Hazardous Processes 24

25. www.issehs.com Conclusions Empower through effective training at regional and site levels Empower through effective training at regional and site levels Adopt cost effective approaches Adopt cost effective approaches Focus on qualitative exposure assessment Focus on qualitative exposure assessment Focus on exposure controls Focus on exposure controls Have strong control at design stage and surrogate monitoring program Have strong control at design stage and surrogate monitoring program Containment validation pre-requisite for TPMs Containment validation pre-requisite for TPMs Remain connected directly or through service provider Remain connected directly or through service provider 25