Realities & Opportunities in Industrialization of Green Chemistry Green Chemistry & Engineering for Pharmaceutical Industry February 05, 2013 Hyderabad Nitesh H. Mehta Newreka Green-Synth Technologies Pvt. Ltd. nitesh.mehta@newreka.co.in
Flow E-Factor in Pharmaceutical Industries Reality of our processes, plants & effluent streams Our current practices for treatment of effluents Magnitude of environmental challenge & its impact Approaches to deal with these challenges Distinguishing Green Chemistry, some myths Opportunities in industrialization of Green Chemistry Conclusions
E-Factor in Pharmaceutical Industries 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 Nature of Pharmaceutical manufacturing: Complex molecules & multi-step synthesis Chemistry Intensive processes Stringent quality & regulatory requirements Source: R A Sheldon The above leads to High E - Factor or Environmental Impact Factor (defined as lbs of waste / lb of product). Need to explore ways to address this challenge of high E - Factor.
E-Factor in Pharmaceutical Industries Stage Average E - Factor Pre Clinical Phase I Phase II Phase III Commercial 185 kg Material Use / kg API 123 kg Material Use / kg API 117 kg Material Use / kg API 96 kg Material Use / kg API 45 kg Material Use / kg API Source Data: ACS GCI Pharmaceutical Roundtable benchmarking exercise 2007
Reality of our processes Step 1 Step 2 Step 3 Step 4 4-5 different chemicals 4-5 different chemicals 4-5 different chemicals 4-5 different chemicals Cocktail of 15-25 different chemicals No option except Effluent Treatment Plant or Incineration
Reality of our plants Mfg. Block for Dedicated Products Manufacturing Site Mfg. Block for Campaign Products Dedicated Product Product 1 Product 2 Product 3 Step 1 Step 2 Step 3 Step 1 Step 2 Step 1 Step 2 Step 3 Step 1 Step 2 Step 3 Step 4
Reality of our effluent streams Each effluent stream has its own: Physical properties colour, ph, temperature Chemical composition organics, inorganics Volume Characteristics COD, BOD, TDS, ammonical nitrogen, etc. Toxicity & hazard What we have is: multiple effluent streams with widely differing quantities & characteristics
Reality of our effluent streams Effluent stream from dedicated products Effluent stream from product 1 Effluent stream from product 2 Effluent stream from product 2 Cocktail of 40-50 different chemicals End-of-the-pipe Treatment (primary & secondary treatment, triple effect evaporator, incineration, solid waste disposal sites, land fill, etc.) Impossible to separate, recover or recycle Our Environment
Impact Impact: huge threat to water bodies & human health Quantity : e.g. approx. 1 bn kgs of API manufactured worldwide E-Factor = 25 to 100 + (ref: R. A. Sheldon) 25 to 100 bn kgs per annum only from Pharma add to it that generated by dyes, pigments agro, textile, mining, etc Practice : Issue : End-of-pipe-treatment (converting one kind of effluent in to other) Toxicity not fully known (Ecotoxicity data available for less than 1% of human pharmaceuticals Ref: journal Regulatory Toxicology Pharmacology, April 2004) Degradation : very slow, impact unknown after degradation Impact on Economics Direct Cost : loss of solvent, raw material & finished product, loss of utilities, treatment cost, higher overheads, loss of business Indirect Cost : unreliable supplies, loss of credibility in market, anxiety, etc.
Approaches to deal with environmental challenges Central Effluent Treatment Plant (CETP) - Capital intensive - Cost centric approach - Ineffective same treatment to wide variety of effluents End-of-the-pipe Treatment (ETP) - Capital intensive - Cost centric approach - Converts one type of effluent in to another Economics & Environmental Footprint Industrial Ecology - Low value creation - Logistics & capacity mismatch issues - Doesn t address problem at source level Green Chemistry - Address problem at source level - Profit centric approach, high value creation - Less capital intensive
Distinguishing Green Chemistry What is Green Chemistry? a science a philosophy an attitude a new domain or branch of chemistry greener way of doing chemistry Way we look at Green Chemistry: an approach a way of thinking place to come from while designing or working on a product or process
Distinguishing Green Chemistry Definition of Green Chemistry: Chemistry & chemical engineering to design chemical products & processes that reduce or eliminate the use or generation of hazardous substances while producing high quality products through safe and efficient manufacturing processes. - Green Chemistry as defined by Green Chemistry Research & Dev. Act of 2005 Definition of Green Engineering: Green Engineering is the development and commercialization of industrial processes that are economically feasible and reduce the risk to human health & environment.
Distinguishing Green Chemistry 12 Principles of Green Chemistry Prevent waste Design safer chemicals and products Design less hazardous chemical syntheses Use renewable feedstocks Use catalysts, not stoichiometric reagents Avoid chemical derivatives Maximize atom economy Use safer solvents and reaction conditions Increase energy efficiency Design chemicals and products to degrade after use Analyze in real time to prevent pollution Minimize the potential for accidents - Environmental Protection Agency, USA 12 Principles of Green Engineering Inherent Rather Than Circumstantial Prevention Instead of Treatment Design for Separation Maximize Efficiency Output-Pulled Versus Input-Pushed Conserve Complexity Durability Rather Than Immortality Meet Need, Minimize Excess Minimize Material Diversity Integrate Material and Energy Flows Design for Commercial "Afterlife" Renewable Rather Than Depleting - Anastas P.T. & Zimmerman J. B., Design through twelve principles of Green Engineering, Env. Sci. Tech. 2003, 37 (5), 94A 101A
Distinguishing Green Chemistry Some common myths about Green Chemistry: Its expensive, not worth it it is theory, doesn t work in real life it takes long time to develop & implement it s a cost center (biggest myth) Performance Green Chemistry Safety & Environment Cost/Economics
Opportunities in industrialization of Green Chemistry Where to start from? Basis of selection? Green Chemistry Metrices: may start with effluent stream with highest E-Factor, PMI, or any other matrices Toxicity Internal Competency Cost pressures Regulatory pressures Demand from customer Resources available Management s priority Ready availability of a particular technology in market place
Opportunities in industrialization of Green Chemistry Medium term e.g. Process Intensification of Unit Processes & Unit Operations (Greener catalyst, etc) Short term e.g. Immediate, workable solution (reduce COD or reduce effluent load by recycling) Long term e.g. Paradigm shift in Engineering like micro reactors Very Long term e.g. designing new route of synthesis starting from renewable feedstock, using Biomimicry
Opportunities in industrialization of Green Chemistry Medium term Time: 2 to 4 years Resources : low to medium Risk: low to medium Short term Time : 1 to 2 years Resources: very low Risk: very low Long term Time: 4 to 8 years Resources: high Risk: high Very Long term Time : 8 to 16 years Resources: very high Risk: very high
Conclusions We have plants which are manufacturing multiple products & each product involves a multi-step process. Each process generates a different type of effluent stream, multiple effluent streams with widely differing quantities & characteristics. Our molecules are complex, very less idea about their environmental consequences. Start wherever you want to or can. But let s START. Create short term & long term strategy to implement Green Chemistry & Green Engineering in to operations. Shift from a cost centre approach to a profit-centric approach. Environmental challenges are opportunities to make PROFITS.
Thank you For resources on Green Chemistry & Green Engineering: Please visit www.industrialgreenchem.com
Barriers to implementation of Green Chemistry Inertia to New Paradigm against the gravity of existing paradigm Technical Barriers: no ecosystem for knowledge-based entrepreneurship Seed capital & funding barriers IP Barriers: protecting IP Market Barriers: awareness, business model Human Barriers: Inertia to change, culture, language Scale-up Barriers: same result in lab as in plant, availability of plant, risk Barriers created by Old Nexus Regulatory Barriers: changes in DMF, FDA & Customer approvals Financial Barriers: working capital for growth
Key Barriers to implementation of Green Chemistry Human Barriers inertia to change from old paradigm to New Paradigm decades of shop-floor experience becomes barrier instead of resource Scale-up Barriers want to see same result in lab as that expected in plant availability of plant to take trials with new technology risk of scale-up who will bear? Market Barriers Lack of awareness about potential of Green Chemistry tool box Some myths like it s expensive, it will increase cost, etc IP Barriers challenge to protect IP little respect for IP in the industry no hesitation in copying idea
Potential Impact of a Green Chemistry Solution Impact of Recycle@Source TM Solutions that are ready with Newreka: No. Product Total Production in (TPM) E-Factor * (kgs waste/kg product) Effluent Quality Minimum No. of Recycles Effluent quantity before & after implementing NRS (litres per month) before after 1 Nevirapine 20 4 Mixture of solvents 500+ 80,000 0 2 Sildenafil Citrate 25 14 Neutral effluent 25 3,50,000 14,000 3 Omeprazole 50 8 Highly alkaline effluent 10 4,00,000 40,000 4 Albendazole 100 8 Highly alkaline effluent 25 8,00,000 32,000 5 Quietiapine 20 6 Neutral effluent 10 1,20,000 12,000 6 H-Acid 2000 26 Acidic effluent 15 5,20,00,000 35,00,000 7 OAPSA 75 13 Acidic effluent 15 9,75,000 65,000 8 FC Acid 50 10 Acidic effluent 15 5,00,000 33,000 9 4-ADAPSA 40 10 Acidic effluent 15 4,00,000 26,000 10 m-phenylene Diamine Sulphonic Acid (MPDSA) 100 5 Acidic effluent 15 5,00,000 33,000 Total Impact on environment : effluent discharge to environment & fresh water consumption of industry reduced by over 50,000 MT per month.