Green Chemistry In Real World Practices Pharmaceutical Industry Experience

Green Chemistry in Real World Practice

Case Study from Pharmaceutical Industry

Nitesh H. MehtaFounder DirectorNewreka Green Synth Technologies Pvt. Ltd.Mumbai, India

nitesh.mehta@newreka.co.in

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

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.

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

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.

E - Factor for Manufacturing Sectors

Sector E - Factor Product Tonnage

Oil Refining ≤ 0.1 106 - 108

Bulk Chemicals 1 – 5 104 – 106

Fine Chemicals 5 – 50+ 102 – 104

Pharmaceuticals 25 – 100+ 10 - 103

Source: R A Sheldon

E - Factor = Total waste generated per kg of Product

E - Factor for Pharmaceutical Sector

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

Source Data: ACS GCI Pharmaceutical Roundtable benchmarking exercise 2007

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 highVolumes involved very low

Phase II Limited No. of moleculesVolumes increased

Phase III No. of molecules further shortlistedVolumes further increased (kgs to ton)

Commercial DMF FiledVolumes 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.

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 H2O / 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)

Solvents61%

Water31%

Reactants & other

reagents8%

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 Companyin 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

Stage IIIChlorination

Stage IVReduction

Stage VStage IINitration

Stage IDiazo. & Hydrolysis

Stage VI

Stage IINitration

Stage IIIChlorination

Stage IVReduction

Stage IDiazo &Hydrolysis

Stage VIStage V

Case Study: Reducing E-Factor & Improving Yield

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

Stage IIIChlorination

Stage IVReduction

Stage VStage IINitration

Stage IDiazo. & Hydrolysis

Stage VI

Stage IINitration

Stage IIIChlorination

Stage IVReduction

Stage IDiazo &Hydrolysis

Stage VIStage V

Case Study: Improving Yield & Reducing E-Factor

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.

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.

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.

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.

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

Opportunities for all of us

Our world needs Chemists & Chemical Engineers operating from larger context of :

“Making a Difference to the world through their work”.

Thank You

&

Wish all of You a

“Greener Future”from

Team Newreka