Green Chemistry in Real World Practice Case Study from Pharmaceutical Industry Nitesh H. Mehta Founder Director Newreka Green Synth Technologies Pvt. Ltd. Mumbai, India [email_address]

sharing context – a possible context for all status of effluents in Pharma Industry application of Green Chemistry brief background about Newreka a case study opportunities Agenda

sharing context – a possible context for all

status of effluents in Pharma Industry

application of Green Chemistry

brief background about Newreka

a case study

opportunities

This is the only World that exists. Real World ?? There is no other world. Then why specifically say “Real World” ?? Green Chemistry in Real World Practice

World of Chemists, Chemical Engineers, Researchers & Scientists: new fields or areas like Nano complex mechanisms fascinating instruments publications …… .etc. May be: to distinguish it from our individual worlds Green Chemistry in Real World Practice None of the above is a problem.

World of Chemists, Chemical Engineers,

Researchers & Scientists:

new fields or areas like Nano

complex mechanisms

fascinating instruments

publications

…… .etc.

None of the above is a problem.

Problem starts, when these become the ultimate objective, instead of larger causes like: reducing environmental footprint of industry making our industry competitive v/s china safety of shopfloor operators drugs being available at affordable prices clean water for all biodegradable/recyclable consumer products energy conservation, optimizing utilitzation …… .etc Green Chemistry in Real World Practice

Problem starts, when these become the ultimate objective, instead of larger causes like:

reducing environmental footprint of industry

making our industry competitive v/s china

safety of shopfloor operators

drugs being available at affordable prices

clean water for all

biodegradable/recyclable consumer products

energy conservation, optimizing utilitzation

…… .etc

World of Chemists, Chemical Engineers, Researchers & Scientists: new fields or areas complex mechanisms fascinating instruments publications …… .etc. Green Chemistry in Real World Practice A possible Context to operate from: All the above are tools or resources, useful for the purpose of serving society, our nation & our world to make it a better place to live.

World of Chemists, Chemical Engineers,

Researchers & Scientists:

new fields or areas

complex mechanisms

fascinating instruments

publications

…… .etc.

A possible Context to operate from:

All the above are tools or resources, useful for the purpose of serving society, our nation & our world to make it a better place to live.

E - Factor for Manufacturing Sectors Source: R A Sheldon E - Factor = Total waste generated per kg of Product Sector E - Factor Product Tonnage Oil Refining ≤ 0.1 10 6 - 10 8 Bulk Chemicals 1 – 5 10 4 – 10 6 Fine Chemicals 5 – 50+ 10 2 – 10 4 Pharmaceuticals 25 – 100+ 10 - 10 3

E - Factor for Pharmaceutical Sector Source Data: ACS GCI Pharmaceutical Roundtable benchmarking exercise 2007 Pharmaceutical Ind. annually makes 1bn kgs drugs Stage Average E - Factor Pre Clinical 185 kg Material Use / kg API Phase I 123 kg Material Use / kg API Phase II 117 kg Material Use / kg API Phase III 96 kg Material Use / kg API Commercial 45 kg Material Use / kg API

Pharmaceutical Ind. annually makes 1bn kgs drugs

When to implement “Green Chemistry”? Pre Clinical No. of molecules very high Phase I No. of molecules still high Volumes involved very low Phase II Limited No. of molecules Volumes increased Phase III No. of molecules further shortlisted Volumes further increased (kgs to ton) Commercial DMF Filed Volumes high (tens of tons) Phase II & Phase III : Right time to start exploring “Green Chemistry” based processes. Will ensure next generation drugs are manufactured through Green Processes.

When to implement “Green Chemistry”? Potential Generics : molecules going off - patent in next 5 years processes being used are “Synthetic Chemistry” based same as was filed in DMF during launch (high E – Factor) volumes expected to increase after patent expiry ( effluents ) price expected to crash after patent expiry (pressure on costing) Generics : patents already expired processes being used are “Synthetic Chemistry” based mostly same as was filed in DMF during launch (high E – Factor) volumes are high (huge quantities of effluents) high competition (pressure on costing) Potential Generics & Generics : ideal cases to start exploring “Green Chemistry” based processes.

Potential Generics : molecules going off - patent in next 5 years

processes being used are “Synthetic Chemistry” based

same as was filed in DMF during launch (high E – Factor)

volumes expected to increase after patent expiry ( effluents )

price expected to crash after patent expiry (pressure on costing)

Generics : patents already expired

processes being used are “Synthetic Chemistry” based

mostly same as was filed in DMF during launch (high E – Factor)

volumes are high (huge quantities of effluents)

high competition (pressure on costing)

Founders Team of Technocrats from IIT Bombay passionate about Nature Foundation Principles of Green Chemistry, Green Engineering & Enviropreneurship Knowledge Base & Over 40,000 experiments conducted by Experience a dedicated team of 50 Chemists & Chemical Engineers. Service Customized & Sustainable Solutions to reduce E-FACTOR * * E-FACTOR = kgs waste generated per kg product Newreka : Brief Introduction

All Unit Processes use H 2 O / Solvent as a Reaction Medium or Extraction Medium Reduction, Condensation, Nitration, Diazotization, Hydrolysis, Methylation, etc. Use is spread across all Industrial Sectors Pharma, Dyes, Pigments, Specialty & Fine Chemicals, Agro, etc. High Volume Products generate huge quantities of waste like H-Acid, DASDA, Paracetamol, Phenylephrine, Pigment CPC, Violet23, Pendimethylene.. Focus: Reducing E-FACTOR ( Recycle of Aqueous & Solvent Effluent Streams)

All Unit Processes use H 2 O / Solvent as a Reaction Medium

or Extraction Medium

Reduction, Condensation, Nitration, Diazotization, Hydrolysis,

Methylation, etc.

Use is spread across all Industrial Sectors

Pharma, Dyes, Pigments, Specialty & Fine Chemicals, Agro, etc.

High Volume Products generate huge quantities of waste

like H-Acid, DASDA, Paracetamol, Phenylephrine, Pigment CPC,

Violet23, Pendimethylene..

Solvent & Water contribute more than 90% of the Reaction Mass Source Data: ACS GCI Pharmaceutical Roundtable benchmarking exercise 2007 Average composition of Effluents will be similar. Recycle of Water & Solvent can take care of 90% of problem. Average Composition of Reaction Mass

Industry Pharmaceutical Customer One of the fastest growing Pharma Company in India Product Anti – Retroviral (or Anti – Aids) Drug Application prevents transfer of virus from mother to child Our Context Enable our customer to supply drug to patients at affordable price so that our next generation is not contaminated with the virus Convert entire API/Drugs synthesis Green Case Study

CONVENTIONAL SYNTHETIC CHEMISTRY PROCESS E-Factor 32 38 28 4 Effluent 1920 TPA 2280 TPA 1680 TPA 240 TPA Total = 6120 TPA (for 60TPA plant) (20,000 kgs per day) GREEN CHEMISTRY SOLUTION BY NEWREKA E-Factor 6 6 1 4 Effluent 360 TPA 360 TPA 60 TPA 240 TPA Total = 1020 TPA Case Study: Reducing E-Factor & Improving Yield Stage III Chlorination Stage IV Reduction Stage V Stage II Nitration Stage I Diazo. & Hydrolysis Stage VI Stage II Nitration Stage III Chlorination Stage IV Reduction Stage I Diazo & Hydrolysis Stage VI Stage V

CONVENTIONAL SYNTHETIC CHEMISTRY PROCESS Th. Yield 1.01 1.41 1.12 0.826 = Overall Yield 1.317 Yield 0.80 0.53 1.05 0.73 = Actual Yield 0.325 (25% of Th.) GREEN CHEMISTRY BASED PROCESS Th. Yield 1.01 1.41 1.12 0.826 Yield 0.95 1.38 1.10 0.79 = Actual Yield 1.140 (86% of Th.) 250% Improvement in Yield Case Study: Improving Yield & Reducing E-Factor Stage III Chlorination Stage IV Reduction Stage V Stage II Nitration Stage I Diazo. & Hydrolysis Stage VI Stage II Nitration Stage III Chlorination Stage IV Reduction Stage I Diazo & Hydrolysis Stage VI Stage V

Case Study: Improving Yield & Reducing E-Factor

Stage I : Diazotization - Hydrolysis 20% higher yield (higher conversion & selectivity, recycle of aq. acidic stream) Decreased fresh water consumption in process by recycle of ML. Elimination of one of the solvents from the process. Replacing a Class I solvent with a safer solvent.

20% higher yield (higher conversion & selectivity, recycle of aq. acidic stream)

Decreased fresh water consumption in process by recycle of ML.

Elimination of one of the solvents from the process.

Replacing a Class I solvent with a safer solvent.

Stage II : Nitration 163% higher yield (higher conversion & selectivity, recycle of aq. stream). Decreased fresh water consumption in process by recycle of ML. Replacing a Class I solvent with a safer solvent.

163% higher yield (higher conversion & selectivity, recycle of aq. stream).

Decreased fresh water consumption in process by recycle of ML.

Replacing a Class I solvent with a safer solvent.

Stage III : Chlorination 16% higher yield (increased conversion & selectivity). Decreased fresh water consumption in process by recycle aq. acidic stream. Replaced one solvent with another which is more effective & much safer to handle. Recovery & reuse of some of the raw materials.

16% higher yield (increased conversion & selectivity).

Decreased fresh water consumption in process by recycle aq. acidic stream.

Replaced one solvent with another which is more effective & much safer to handle.

Recovery & reuse of some of the raw materials.

Stage III : Reduction 23% higher yield (increased conversion & selectivity). Eliminated use of two solvents from the process by using Water as the reaction & extraction medium Decreased fresh water consumption in process by recycle of neutral ML. Safer process since solvents are eliminated & high pressure reaction replaced by atmospheric pressure process.

23% higher yield (increased conversion & selectivity).

Eliminated use of two solvents from the process by using Water as the reaction &

extraction medium

Decreased fresh water consumption in process by recycle of neutral ML.

Safer process since solvents are eliminated & high pressure reaction replaced by

atmospheric pressure process.

Inside the larger context of serving our society, our nation & our Real World, there are following opportunities for us: Industries: Pharma, Dyes, Pigment, Agro, etc. e.g. Pharma – 1 billion kgs per annum of Drugs Products: huge volumes & huge E-Factors Chemistries: Friedel Craft, Sulphonations, etc. Effluent Streams: Solid, Liquid, Gaseous Developing GC Tools: platform technologies Opportunities for all of us

Inside the larger context of serving our society, our nation & our Real World, there are following opportunities for us:

Industries: Pharma, Dyes, Pigment, Agro, etc.

e.g. Pharma – 1 billion kgs per annum of Drugs

Products: huge volumes & huge E-Factors

Chemistries: Friedel Craft, Sulphonations, etc.

Effluent Streams: Solid, Liquid, Gaseous

Developing GC Tools: platform technologies

Our world needs Chemists & Chemical Engineers operating from larger context of : “ Making a Difference to the world through their work”. Opportunities for all of us

Thank You & Wish all of You a “ Greener Future” from Team Newreka