Académique Documents
Professionnel Documents
Culture Documents
S. Page No.
Description
No.
1.0 Executive Summary 1
1.1 Salient Features of the Project 1
2.0 Introduction 2
2.1 Identification of the Project and project proponent 2
2.2 Brief description of Nature of the Project 3
2.3 Need for the Project and its importance to the country 4
and or region
2.4 Demand and Supply Gap 4
2.5 Imports Vs. Indigenous production, Export Possibility, 4
Domestic/Export Markets
2.6 Employment Generation due to the proposed project 5
i
S. Page No.
Description
No.
4.8 Social Infrastructure 14
5.0 Planning 14
5.1 Planning Concept 14
5.2 Population Projection 14
5.3 Land use planning 14
5.4 Assessment of Infrastructure Demand 15
5.5 Amenities/Facilities 15
6.0 Proposed Infrastructure 15
6.1 Industrial Area 15
6.2 Residential Area 15
6.3 Green Belt 15
6.4 Social Infrastructure 16
6.5 Connectivity 16
6.6 Drinking Water management 16
6.7 Sewerage System 16
6.8 Industrial Waste Management 16
6.9 Hazardous/ Solid Waste Management 18
6.10 Power Requirement & Supply / Source 18
7.0 Rehabilitation and Resettlement (R&R) Plan 18
8.0 Project Schedule & Cost Estimates 19
8.1 Time Schedule for the project construction 19
8.2 Estimated project cost 19
9.0 Analysis of proposal (Final Recommendations) 19
9.1 Budgetary allocation for Pollution Control Measures 19
ii
List of Tables
iii
LIST of Annexures
Annexure
Title Page
No.
I Certificate of Incorporation 21
II General location of the Proposed Project 22
III Specific Location of the Proposed Project 23
IV Google map showing the coordinates 24
V Proposed Plant Layout 25
VI Typical process description & Flowchart for proposed products 26-74
VII Raw Materials required for the manufacture of Proposed products 75-98
VIII Hazardous chemicals list 99
IX Water analysis report 100
X Proposed Effluent Treatment Plant Flow Diagram 101
XI Schematic Flow Sheet for EIA Procedure 102-103
XII Topomap of 10 km Radius of Proposed Project 104
XIII Soil Analysis Report 105
Other Annexures
XIV Agreement of Sale 106-109
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
M/s. Orygamus Laboratories Pvt. Ltd., proposes its Active Pharmaceutical Ingredients
(APIs) and API Intermediates manufacturing with R&D facility at Sy. 208/17 & 208/18 at
Ramalingampally (V), Bommalaramaram (M), Nalgonda District, Telangana State with a total
investment of Rs. 45 crores.
The proposed project falls under the Category ‘A’ project or activity 5(f) according to the
EIA Notification 2006.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
• Diesel of about 320 lit / hr will be used in the proposed 1000 & 500 KVA D.G. Sets and 2 lak
K.cal/hr Thermic Fluid Heater.
• Industry will provide dual scrubbers based on the characteristics of process emissions.
Economizer, multi-cyclone separator & bag filter for Boiler emissions will be provided to
reduce the particulate emissions into atmosphere.
• The wastewater generated from the plant will be about 152 KLD from process, washing,
utilities, DM regeneration, Scrubber, Q.C, R&D and domestic wastewater.
• The effluent will be pumped to the above ground level R.C.C lined tanks for storage and
neutralization then sent to proposed ETP-ZLD of 200 KLD capacity within the premises.
• Domestic wastewater will be sent to septic tank and the overflow to ETP - ZLD.
• Hazardous waste will be segregated and collected in the HDPE drums / bags as appropriate
and will be stored in the covered and raised platform with provision of leachate collection
system.
• Solid waste like boiler ash will be sent to cement brick manufacturers.
• Compressors, Boilers and DG sets will be the major noise generating units in the plant. Out
of these, the generator will be functioning at the time of power failure. D.G. sets will be built-
in acoustic enclosures to minimize the noise levels. However the workers in this area will be
provided with ear muffs.
Industry has uploaded Form-I along with draft Terms of Reference (ToR) in MoEF&CC
website, in the process of obtaining ToR for preparation of EIA, in line with issue of Environmental
Clearance. Hence, a technical pre-feasibility report highlighting the proposed project and the
various operations including waste generation and mitigation measures are prepared & submitted
to the Environmental Appraisal Committee (EAC) for issuing ToR.
2.0 Introduction
2.1 Identification of the Project and Project Proponent
M/s. Orygamus Laboratories Pvt. Ltd., proposed greenfield project of manufacturing Active
Pharmaceuticals Ingredients (APIs) and API Intermediates manufacturing with R&D facility in an
area of 5.45 Ha located at Ramalingampally Village, Bommalaramaram Mandal, Nalgonda District,
Telangana State. A copy of the Certificate of the Incorporation from Registrar of Companies is
enclosed as Annexure-I. The proposal is to obtain Environmental Clearance from the Ministry of
Environment, Forests and Climate Change (MoEF&CC) and Consent for Establishment from
TSPCB.
• Total production capacity is 453.6 TPA from proposed 38 APIs and API intermediates on
campaign basis i.e., any 5 products at a time with R&D will be manufactured.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
Project Proponent:
• Dr. D. Srinivasa Reddy is the founder and Managing Director of Orygamus Laboratories Pvt.
Ltd., (Optimus Group), a global player in Specialty API and API Intermediates in API industry.
His vision has been to leverage technological advancements in drug development and
manufacturing towards realizing quicker cycles, cost-effective drugs and affordable healthcare.
He started Optimus (formerly Suryakiran) in 2004 with the intention to realize this goal. He
started his career by technical consulting assignments for other pharmaceutical companies in
India and abroad came to be recognized for expertise in developing and manufacturing new
molecules.
• Mr. V V Srinivasa Rao has 25 years of experience with leading pharmaceutical organizations
where he spearheaded innovative and advance research in Organic Chemistry. Mr. Rao has a
Master’s degree in Chemistry. He has been associated with Optimus group since 2005. His
efforts are very significant in the Company's growth in last 10 years. He is part of the Executive
Board since 2008.
• Mr. S. Bajeesaida Director and is responsible for the Technical activity of the company. He
holds a graduation in Engineering and has over 28 years of experience in Engineering and
Projects functions with some of the top Pharma companies in India. He is overall responsible
for achieving the company’s goals and objectives in terms of planning, strategies, reach and
regulatory milestones.
The project proponent proposed its API manufacturing unit. As per EIA Notification 2006,
the project is 5 (f) Synthetic Organic Chemical Industry (Bulk Drug (API) & Intermediates). The
products manufactured are used in API formulation industry and the therapeutic category of the
products is Antivertigo, Anti-Alzheimer's, Antithyroid, Antiasthmatic, Analgesic, Antidepressant,
Antiglaucoma, Antidyskinetic, Anti-viral, Anti-inflammatory, Antifibrotic, Antineoplastic,
Antiangiogenic, Antiglaucoma, Anticholinergic, Antiepileptic, Antibiotic, Antihyperlipidemic,
Anticonvulsant, Analgesic, Antidepressant, Antiasthmatic, Anti-multiple sclerosis agent,
Anticoagulant etc., which are applicable for human consumption around the world after formulation
activity.
The manufacturing process of APIs consists of chemical synthesis and multiple stage of
processing extending to maximum of 13 stages involving different types of chemical reactions. The
entire process operations are operated by various technical, skilled and unskilled persons with due
care to be met various standards prescribed by authorities.
Technology for manufacturing the products listed under proposed project is available from
in-house R&D & private consultants and proposes to adopt new technologies and techniques that
are continuously refined in every stage of manufacturing to meet global standards. Industry will
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
implement the proven technologies in the R&D for the cost effective & environment friendly
practices.
2.3 Need for the Project and its Importance to the Country and or Region
India has achieved an eminent global position in pharma sector. The Indian
pharmaceuticals market is third largest in terms of volume and thirteen largest in terms of
value, as per a pharmaceuticals sector analysis report by equity master.
The market is dominated majorly by branded generics which constitute nearly 70% to 80%
of the market. The Indian pharmaceutical industry is estimated to grow at 20 per cent
compound annual growth rate (CAGR) over the next five years, as per India Ratings. The
domestic pharma growth rate was 11.9 per cent in October 2014.
The Government of India has unveiled 'Pharma Vision 2020' aimed at making India a
global leader in end-to-end drug manufacture.
Telangana has proposed to set up India's largest integrated pharmaceutical city spread
over 11,000 acres near Hyderabad, complete with effluent treatment plants and a township
for employees, in a bid to attract investment of Rs 30,000 crore (US$ 4.85 billion) in
phases.
Hyderabad, which is known as the bulk drug capital of India, accounts for nearly a fifth of
India's exports of drugs, which stood at Rs 90,000 crore (US$ 14.56 billion) in 2013-14.
The products manufacture by the proponent has demand from China, Japan, Middle East,
Latin American countries and other Asian countries etc. In addition, the products are consumed in
domestic market by Dr. Reddy labs, NATCO, Pfizer, Cipla, Mylan, Novartis etc. It is reported that
there is increase in the consumption of these products by about 5-6% every year. As Indian
industries are importing from neighbouring countries and western countries, indicates the gap in
the demand and supply of the products in the domestic markets.
Presently China is dominating in the API (bulk drug) market the world over. India is
importing all major intermediate chemicals required for manufacturing lifesaving drugs i.e., Anti-
Cancer Drugs, Anti ulcerative, etc. We are importing from China – the Third generation Antibiotics
mainly Cephalosporin intermediates that are of very high value. Most of our imports are from
Chinese companies and thus we are losing our valuable foreign reserves to China. As mentioned
above the imports have gone up from $ 2.9 billion in 2011 to about $ 4.6 billion in 2012 on account
of APIs, Pharmaceuticals and fine chemicals. During the same period the imports of formulations
has also doubled. The Chinese, American and European markets play a very vital role in the
supply of these products to our country. This clearly indicates that there is tremendous scope for
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
developing the indigenous products by reducing the imports and thus saving the foreign exchange
reserves of the country. This potential can be utilized to the fullest extent possible by increasing
the production capacity of the existing industries or by establishing new industries to meet the
market demand of the products.
As it is a well-known fact that Indian products are well accepted abroad for its quality and
marketing flexibility. The exports from the Indian companies to other foreign countries such as
Europe, America, Japan and other African countries has been increasing from Rs.8007 in 2005 to
Rs.16565 Crores in 2009. This shows the acceptability of the products produced in India. The
formulations market has shown a tremendous increase in the exports from about Rs.9500 to
Rs.23700 Crores during the same period. However, the basic raw material for formulations is
APIs. Hence, this sector has a tremendous potential of indigenous market as well as export market
and the promotion of such projects will not only help by way of generation of employment but also
by generation of foreign currency reserves for the country. The figures mentioned above are
sourced from BDMA.
3.2 Location
The unit is located at Sy. 208/17 & 208/18, Ramalingampally (V), Bommalaramaram (M),
Nalgonda District, Telangana State. The proposed site is located in an intersection of Latitude
17°33'48"N & Longitude 78°42'23"E. The study area represents Rural Environment.
The map showing general location, specific location, Google map showing the Coordinates
and plant layout of the Project is enclosed at Annexures II, III, IV, and V respectively.
This proposed project is in the area of 5.45 Ha at Sy. Nos. 208/17 & 208/18,
Ramalingampally (V), Bommalaramaram (M), Nalgonda District, Telangana State. Considering
other acceptable sites, Proponent has chosen this project site because the site is barren rocky
land and surrounded by chemical and stone crusher industries.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
Production Capacity: 453.6 TPA from 38 APIs & API intermediates and R&D activity
(5 products will be manufactured at a time).
Products: The proposed products and by-products along with its production capacities are
presented in Table 1.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
Therapeutic Category
SI. Quantity Quantity
Product / Intermediate to the
No. (kg/day) (TPA)
product
14 Imatinib Mesylate 41.67 15 Antineoplastic
15 Gefitinib 33.33 12 Antineoplastic
16. Erlotinib 50 18 Antineoplastic
17 Dasatinib 16.67 6 Antineoplastic
18 Atazanavir Sulfate 166.67 60 Antiviral
19 Pomalidomide 8.33 3 Antineoplastic
20 Lenalidomide 16.67 6 Antiangiogenic
21 Latanoprost 20.83 7.5 Antiglaucoma
22 Solifenacin Succinate 41.67 15 Anticholinergic
23 Cabazitaxel 8.33 3 Antineoplastic
24 Entecavir 41.67 15 Antiviral
25 Perampanel 8.33 3 Antiepileptic
1-((2R,3R,4R,5R)-3-fluoro-4-
hydroxy-5-(hydroxymethyl)-3- Sofosbuvir
26 23.33 8.4
methyl tetrahydrofuran-2- Intermediate
yl)pyrimidine-2,4(1H,3H)-dione
(S)-Isopropyl-2-(((R)-(perfluoro
Sofosbuvir
27 phenoxy)(phenoxy) phosphoryl) 41.67 15
Intermediate
amino) propanoate
28 Daclatasvir Dihydrochloride 41.67 15 Antiviral
29 Rifaximin 125 45 Antibiotic
30 Linezolid 250 90 Antibiotic
31 Rosuvastatin Calcium 116.67 42 Antihyperlipidemic
32 Pregabalin 83.33 30 Anticonvulsant
33 Flurbiprofen 108.33 39 Analgesic
34 Vilazodone Hydrochloride 37.5 13.5 Antidepressant
35 Montelukast Sodium 166.67 60 Antiasthmatic
Anti-multiple sclerosis
36 Teriflunomide 41.67 15
agent
37 Abiraterone Acetate 125 45 Antineoplastic
38 Dabigatran Etexilate Mesylate 166.67 60 Anticoagulant
Total Production Capacity
1250 450
(Maximum 5 products at a time).
R&D activity 10 3.6
Total Production Capacity
(Maximum 5 products at a time and 1260 453.6
R&D activity)
List of By-Products
SI. Quantity Quantity Generated from the
By-product
No. (kg/day) (TPA) product
1 Selenium 159 57 TPA Fenoterol
2 Aluminium Hydroxide sol. (8%) 681 245 TPA Hydrobromide
Scrubbing liquid from
3 Dil. HCl 20% 2029 730 TPA
process emissions
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
The raw materials required for the manufacture of proposed products are the chemicals
and the fuel.
• The APIs & API Intermediates manufacturing involve the use of various chemicals and
organic solvents either directly as reactant or for extraction of a product of interest from the
reaction mixture.
• Coal consumption will be 64 TPD for the proposed 12 and 4 TPH coal fired boilers
• About 320 lit/hr diesel will be used at full operation load in the proposed 1000 & 500 KVA
DG sets and 2 lac.Kcal/hr TFH.
• The total power requirement of the proposed plant is 1000 KVA. DG sets are used as
standby during power failure.
• Mode of transportation of all raw materials and finished products from the project site is by
road to local markets and by road / rail / sea if exported / imported.
The chemicals (raw materials) required for the manufacture of proposed products is
presented at Annexure – VII and Hazardous chemicals list is presented at Annexure – VIII.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
The total fresh water requirement is about 328 KLD which will be met from Groundwater
through from Bore well/ tankers. The proposal is to minimize the effect on the level of water table
by practicing reuse / recycling of the treated water wherever possible thereby reducing the fresh
water requirement. Water analysis report of the raw water at project is enclosed as Annexure–IX.
The total power requirement will be met from Telangana State Southern Power Distribution
Committee (TSSPDC) limited. Coal and Diesel will be procured from the distribution sources
closer to the project.
3.9.1 Water requirement and Wastewater Generation and their Management / Disposal
The proposed water requirement and wastewater generation and its proposed treatment is
presented in Table 2. The sources of wastewater generation are from the process, floor & reactor
washes, utilities, Q.C, R&D, scrubber and plant domestic waste. Total proposed wastewater will be
152 KLD, which will be segregated into HTDS/HCOD & LTDS/LCOD and collected by gravity into
a collection tank separately. This individual effluent will be pumped to the above ground level
R.C.C lined tanks for storage and neutralization then sent to ETP-ZLD. The effluents segregated
quantity, characteristics and treatment flow is briefly presented in Table 3.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
91 0 64 13
(Blow down)
Boiler
(12 & 4TPH) 14 Utilities
(24% (LTDS/LCOD)
(MEE steam
make up) condensate)
Cooling Tower 20
106 134 220
4000 TR (Bleed)
DM
5 5 HTDS / LCOD
Regeneration
Scrubber
8 8 HTDS / LCOD
(4 Nos.)
Q.C and R&D 5 5 LTDS/LCOD
Domestic (300
15 3 12 LTDS/LCOD
nos @50 lpcd)
Greenbelt
25 - 25 - --
(5 acres)
Reuse:
328 134 310 152 Stripper Condensate : 1 KLD
Moisture in Salt and ETP
Total Sludge : 2 KLD
Water loss in ETP 15 KLD
462 462 (Total water loss is 18 KLD =
12 %)
Note: 55 KLD is 58.9 Tons consists of 55.3 KLD effluent and 3.6 Tons of salts (Max. on various
combinations) as per material balance.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
Proposed ETP facility is enclosed as Annexure-X. All the treatment tanks etc., will be
constructed / installed above the ground with water proof lining. This individual effluent will be
pumped to the above ground level R.C.C lined tanks for storage and neutralization then sent to
proposed ETP-ZLD of 200 KLD capacity within the premises.
ETP – ZLD facility with primary (equalization and neutralization), secondary (stripper with
MEE, ATFD & biological) and tertiary treatment (PSF, ACF & R.O) will be provided. Domestic
wastewater will be sent to septic tank and the overflow to ETP (biological treatment). Concentrate
from MEE system will be sent to ATFD and the salts from the evaporation system will be collected
and sent to TSDF, Dundigal for safe disposal.
Solid waste will be segregated, detoxified and collected in the HDPE Drums / Bags and will
be stored in the extended covered and raised platform with Leachate collection system. The
proposed solid waste and other waste generated, handling and disposal method from the various
stages of APIs & API intermediates manufacturing plant is presented in the Table 4. Spillages
such as wastewater / solid wastes / raw material are possible and the risk of this would be limited
to within the premises of the manufacturing facility. A precautionary measure like spillage control
management is practiced in the industry.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
Proposed
Sl. Handling
Source Quantity Disposal
No. Method
(TPD)
Stored in Sold to Cement Brick
7. Boiler Ash 25.6 covered Manufacturers
area
Other Hazardous Waste generation from the Plant
Detoxified Container / Disposed to TSPCB
500 Nos / Designated
8. Liners drums / HDPE Authorized agencies
month covered
Carboys / Fiber Drums after complete
area
9. PP Bags 200 Kg/ month detoxification
Spent solvents Stored in Sent to Inhouse
10. (with moisture) 80 KLD Drums / Solvent Recovery
(Solvents 77 + water 3) Tanks System
Recovered Solvents Tanks/ Reuse in process /
11. 74 KLD
from spent solvents Drums Authorized Recyclers
Spent Mixed solvents Stored in Sent to TSPCB
12. (from SRS + ETP) 4 KLD Drums / Authorized Recyclers /
(3 + 1) Tanks Cement industries
Sent to TSPCB
Stored in Authorized agencies
13. Waste oils & Grease 2 KL/A
Drums for reprocessing /
recycling.
Designated
Used Lead acid 100 Nos. / Sent to suppliers on
14. covered
Batteries annum buy-back basis.
area
Misc. Waste Stored in
15. 45 TPA TSDF
(spill control waste) Drums
Sent to suppliers on
16. Spent catalyst 150 TPA
Stored in buy back basis
Drums Used in ETP for
17. Spent Hydrochloric Acid 68 TPA
Neutralization
* Solid waste quantities maximum on various combinations i.e., maximum 5 campaign products at
a point of time with R&D activity.
The schematic flow sheet for EIA procedure is depicted as Annexure -XI.
The proposed project site is about 0.5 km (E) from Rangapuram village, 1.3 km (NW) from
Ramalingampally; 8 km (SW) from Hyderabad ORR; 3.1 km (E) from Bommalaramaram; 3.5 km
(SSW) from Keesaraguta; 46 km (SW) from Shamshabad Airport, Hyderabad; 79 km (SE) from
direction Nalgonda;
Total land is 5.45 Ha. Industry has entered agreement with land owner and will be in
possession by February 2016.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
4.3 Topography
The proposed land use pattern of project area (core area) 5.45 Ha. Industrial land and
shortest distance of environmental components in buffer area from the project periphery is given in
Table 5.
The soil in the project site is Red and in the study area is mostly red in colour, containing
46.86% sand, 38.22% silt and 14.92% clay. The soil analysis report of the project site is enclosed
at Annexure-XIII.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
The area enjoys pleasant, warm and dry climate. The coldest season is during December
and January, where the temperature touch a minimum of 12-16°C and warmest period is during
the month of April to May when the Mercury shoots up to 43 - 46 °C.
The area experiences the maximum rainfall during the months of June to September and a
little rainfall during October and November due to North-East monsoon. Apart from these,
occasional rainfall is obtained from cyclonic storms and depression originating in the Bay of
Bengal. The average annual rainfall of the area is 786 mm. The rainfall is erratic and long period of
dry spells leading to drought conditions are frequent and periodic. The relative humidity ranges
between 75-95% during monsoon and 35-40% in summer afternoon.
5.0 Planning
5.1 Planning Concept
Type of Industry: The proposed project is of APIs & API Intermediates manufacturing industry
with R&D facility.
Facilities: Facilities required for the project will be provided as per requirement.
Transportation: Transportation of raw material and final products is done via roads as the
proposed project is well connected with roads, rail and airways.
Town and Country Planning Classification: This industry land is private land and will be
converted to industrial use.
The unit has been proposed in the total area of 5.45 Ha. Land use pattern of the Project
area is given in Table 6.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
There is no much demand for infrastructure for the proposed project as all infrastructure is
available near the project site.
5.5 Amenities/Facilities
Industry will provide the following amenities / facilities in the proposed project.
• Canteen
• Potable drinking water
• Training block
• Laying of Black top / Concrete internal roads
• Fire hydrant facility
• Eye/body wash showers
• First Aid kits at all prominent places.
• Head nurse for emergency medication.
• Rest Room for employees
• Seating facilities for those employees who do their work standing and ergonomically
designed sitting facilities for those who do their work sitting
• Pre-employment and routine medical examinations and the necessary follow up actions
• Communication systems like Phone, Internet with safety measures, etc.
• Security system at the entrance etc.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
6.5 Connectivity
There is no change in connectivity compare to current facility.
6.6 Drinking Water Management
Potable drinking water will be provided to all employees. The source of drinking water is
Groundwater.
Storage system needs to meet the project demand. The management of these wastes is to
be handled very sensitively and by adopting proper segregation techniques.
Liquid Waste Management: The liquid wastes from the various industrial activities will be
segregated and send to ETP-ZLD.
Manufacturing of APIs and API intermediates will result in gaseous emissions. Maximum
Process emissions from proposed products on campaign basis are given in Table 7. Proposed
gaseous emissions will be scrubbed in two stage scrubber with water or other liquid based on the
characteristics of gases. Dil HCl (20%) will be sold as by-product.
Maximum Quantity on
Sl. Process
various combinations Treatment Method
No. Emission
(kg/day)
1. HCl 405.83 • Scrubbed with water
2. SO2 120.83 • Scrubbed with caustic sol.
3. Methyl Chloride 182.58 • Scrubbed using caustic sol
4. CO2 388.63 • Dispersed into atmosphere
5. H2 23.17 • Diffused with flame arrestor
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
Proper earthing will be provided to all the electrical equipment and the joints / connections
wherever solvent handling is done.
Reactor and solvent handling pump will have mechanical seals to prevent leakage.
The industry will take measures for reduction of fugitive emissions and further reduction
industry will provided vent condensers to the tanks.
Chilled brine circulation will be carried out to condensate the solvent vapor and to the
receivers of the solvent vapors which ensures the maximum recovery.
Solvent vapours from the Centrifuge and Catch pots will connect to vent condensers.
The height of the solvent receiver tank vent is above production block roof level and the
diameter is 20 mm.
Flame proof fitting / equipments / pumps / lighting will be used wherever solvents are used.
The solvent storage tanks will be provided with breather valve to prevent losses.
Boilers and DG sets are the two main sources contributing to emissions from the plant. The
proposed 12 & 4 TPH coal fired boilers and 2 lak Kcal/hr TFH will be which will be used for steam
requirements. Proposed 1000 KVA and 500 KVA DG Sets will be used as standby power during
power failures. The emissions from the boiler are given in Table 8.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
Multi-cyclone separator followed by Bag filter will be installed to control the particulate (PM)
emissions within statutory limit of 115 mg/Nm3. To facilitate wider dispersion of pollutants,
40m & 30m height stack each will be installed.
The NOx emissions from the boilers will be controlled by controlling combustion measures,
which will be approached by way of low NOx burners or by air stagging in boiler. The NOx
emissions will be restricted to below 500 mg/Nm3.
Stacks will be provided to proposed 2 lak.cal/hr TFH, 500 & 1000 KVA D.G sets as per
CPCB / SPCB Guidelines.
Fugitive dust will be controlled by adopting dust extraction and dust suppression measures
and development of greenbelt along the periphery of the proposed Boiler area.
Noise Management:
• Compressors, Boilers and DG sets will be the major noise generating units in the plant.
• The noise levels of the DG sets will be well within the limits as these will be installed with
acoustic enclosures. Workers will always be provided with ear muffs.
• All the equipment in the plant would be designed to have a total noise level not exceeding
85-90 dB(A) as per the requirement of OSHA (Occupational Safety and Health
Administration) standards.
• Solid waste mainly segregated into process organic residues, inorganic salts, boiler ash
spent mixed unrecoverable solvents and spent carbon.
• The organic residues, Spent carbon & Spent mixed unrecoverable solvents can be
disposed off to Cement plants as recommended by CPCB for use as alternate fuels either
in the solid or liquid form.
• Boiler ash will be sold to cement brick manufacturers.
• Inorganic salts are to be sent for landfill at HWMP – TSDF.
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
The timelines for commencement of proposed construction activity will be from April 2017
as it is expected that the proposed project will be in a position to obtain Environmental Clearance
& Consent for Establishment for the project. In 2017-18 the commercial production is expected to
be commenced.
Overall estimated cost involved in the total project like land, building, plant & machinery is
Rs. 45 Crores. Total capital cost allocated towards environmental pollution control measures is
Rs. 9.2 Crores and the Recurring cost will be about Rs.7 Crores per annum.
• The proposed project will result in growth of surrounding area by generating direct and
indirect employment to local people. Around 300 members will be benefitted due to the
proposed project.
• Under the Corporate Social Responsibility the Industry will develop a policy of developing the
villages in the vicinity by identifying the requirements.
• Industry will provide the Safety, Health & Environment Department and also engage
recognized laboratories to carry out all necessary monitoring parameters for its activities.
• The segregated (HTDS / LTDS) wastewater will regularly analyzed before and after
treatment in ETP-ZLD.
• Qualified staff will be appointed for the purpose of Operation and Maintenance of the
pollution control facilities.
• Stand-by facilities will be provided to all the pumps so as to ensure fail proof treatment,
handling and disposal.
The management will set aside adequate funds in its budget to fully meet the stated
objectives of the environmental policy. The proposed capital equipment for environmental
management include effluent treatment plants, pipelines and channels for wastewater discharge,
air pollution control, solid/hazardous waste storage facilities, Noise attenuation, Occupation health
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M/s. Orygamus Laboratories Pvt. Ltd. Pre-Feasibility Report
/ safety, greenbelt development and the environment laboratory. The break-up of budgetary
allocation for various control measures is presented in Table 9.
20
ANNEXURES
ANNEXURE - I
21
General Location Map ANNEXURE - II
Telangana state
Project Site
(1)Bommalaramaram (M), Nalgonda District.22
ANNEXURE - III
Specific Location (Route map)
24
ANNEXURE - V
NORTH
W E
6 M WIDE ROAD
5 WAREHOUSE 40.0 20.0 SECURITY
12 X 10 M
8 M WIDE ROAD
11 TANK FORM 30.0 15.0
PRODUCTION BLOCK-1 GREEN BELT
12 ETP 40.0 20.0 70 X 20 M
LAWN
13 DISTILLATION COLUMN 20.0 20.0
6 M WIDE ROAD
6 M WIDE ROAD
6 M WIDE ROAD
PRODUCTION BLOCK-3
70 X 20 M
LAWN
TANK FORM
30 X 15 M
GREEN BELT
6 M WIDE ROAD
GREEN BELT
6 M WIDE ROAD
LAWN/OPEN AREA
ETP
20 X 40 M 90X40M
GREEN BELT
100X30M
20 X 20 M
70 X 20 M
6 M WIDE ROAD
LAWN/OPEN AREA
86X30M
BOILER
20 X 15M
Total 54459.2
53366.74 100.00 Revision History First Issue
25
ANNEXURE - VI
PRODUCT : Betahistine
Description :
Stage-2 : 3-Pyridin-2-yl acrylic acid is reduced with Hydrogen on Palladium Carbon and treated with Ammonium
Hydroxide in presence of Methanol solvent media to get 3-Pyridin-2-yl propionamide.
Stage-3 : 3-Pyridin-2-yl propionamide is reacted with Bromine and Sodium Methoxide in presence of Methanol
solvent media to get (2-Pyridin-2-yl ethyl) carbamic acid methyl ester.
Stage-4 : (2-Pyridin-2-yl ethyl) carbamic acid methyl ester is heated with Potassium Hydroxide to get 2-Pyridin-2-
yl ethylamine.
Stage-5 : 2-Pyridin-2-yl ethylamine reacted with Methyl Iodide in presence of Sodium Carbonate in Toluene
solvent media to get Betahistine.
Flow Chart
2-Hydroxy-1-Pyridinyl-3- Sol.Recovery
trichloro Propane Evaporation Loss
Methanol (90%) Stage I Organic Residue
Sulfuric Acid Inorgainc Solid Waste
Process Emissions
Stage-1 Sol.Recovery
Hydrogen Evaporation Loss
Palladium Carbon Stage II Effluent
Ammonium Hydroxide (28%) Organic Residue
Methanol Process Emissions
Stage-2
Bromine Sol.Recovery
Sodium Methoxide Stage III Evaporation Loss
Methanol Effluent
Water
Stage-3
Potassium Hydroxide Stage IV Effluent
DM Water
Stage-4
Toluene Sol.Recovery
Sodium Carbonate Stage V Evaporation Loss
Methyl Iodide Effluent
DM Water
Betahistine
26
ANNEXURE - VI
PRODUCT : Rivastigmine
Description :
Stage-1 : a-m-Hydroxy phenyl ethyl dimethylamine in dry Acetonitrile reacted with n-Ethyl methyl carbomyl
chloride in presence of Sodium Hydride and Diethylether to get Rivastigmine.
Flow Chart
a-m-Hydroxy phenyl ethyl
dimethy amine
Acetonitrile Sol.Recovery
N-Ethyl methyl Carbomyl Evaporation Loss
chloride Stage I
Effluent
Diethyl ether Organic Residue
Sodium Hydride (60%) Process Emissions
Water
Rivastigmine
27
ANNEXURE - VI
PRODUCT : L-Thyroxine
Description :
Stage-1 : 2-Acetylamino-3-(4-hydroxy-3,5-diiodo phenyl) propionic acid ethyl ester under goes digestive
coupling reaction it was suspended in Boric acid and Ethanol and digested with Sodium Hydroxide to get
2-Acetylamino-3-[4-(4-hydroxy-3,5-diiodo phenoxy)-3,5-diiodo phenyl] propionic acid ethyl ester.
Flow Chart
2-Acetylamino-3-(4-hydroxy-
3,5-diiodo phenyl) propionic
acid ethyl ester Sol.Recovery
Boric Acid Stage I Evaporation Loss
Ethanol Effluent
Sodium Hydroxide Organic Residue
Water
Stage-1
Acetic Acid
Stage II Effluent
Hydrochloric Acid (36%)
Water
L-Thyroxine
28
ANNEXURE - VI
Description :
Stage-1 : 3,5-Dibenzyloxy Acetophenone is reacted with Selenium Dioxide in presence of 1,4-Dioxane to get (3,5-
Bis benzyloxy phenyl) oxo acetaldehyde.
Stage-2 : (3,5-Bis benzyloxy phenyl) oxo acetaldehyde is reacted with 4-Methoxy phenyl-2-aminopropane in
presence of Methanol to get amine compound and it is reduced with Sodium Borohydride in presence of
Hydrochloric acid to get 1-(3,5-Bis benzyloxy phenyl)-2-[2-(4-methoxy phenyl)-1-methyl ethylamino] ethanol.
Stage-3 : 1-(3,5-Bis benzyloxy phenyl)-2-[2-(4-methoxy phenyl)-1-methyl ethylamino] ethanol is treated with
Aluminum Chloride in presence of Toluene to get 4-{2-[2-(3,5-Bis benzyloxy phenyl)-2-hydroxy ethylamino] propyl}
phenol.
Stage-4 : 4-{2-[2-(3,5-Bis benzyloxy phenyl)-2-hydroxy ethylamino] propyl} phenol is treated with Maleic Acid in
presence of Ethyl Acetate to form Maleate Salt then basified with Sodium Bicarbonate to get 4-{2-[2-(3,5-Bis
benzyloxy phenyl)-2-hydroxy ethylamino] propyl} phenol.
Stage-5 : 4-{2-[2-(3,5-Bis benzyloxy phenyl)-2-hydroxy ethylamino] propyl} phenol is debenzylated with Hydrogen on
Palldium Carbon in presence of Ethyl Acetate to get Fenoterol.
Stage-6 : Fenoterol is treated with Hydrogen Bromide in Acetic Acid (33%) in presence of Isopropyl Alcohol to get
Fenoterol Hydrobromide.
29
ANNEXURE - VI
Flow Chart
3,5-Dibenzyloxy Acetophenone By-Product
Selenium Dioxide Sol.Recovery
Stage I
1,4-Dioxane Evaporation Loss
Organic Residue
Stage-1
4-Methoxy phenyl-2-
aminopropane Sol.Recovery
Methanol Stage II Evaporation Loss
Sodium Borohydride Effluent
Hydrochloric Acid (36%) Organic Residue
Water
Stage-2 Sol.Recovery
Aluminum Chloride Evaporation Loss
Toluene Stage III Aqueous Send to Auth. Party
Water Organic Residue
Process Emissions
Stage-3 Sol.Recovery
Maleic Acid Evaporation Loss
Ethyl Acetate Stage IV Effluent
Sodium Bicarbonate Organic Residue
DM Water Process Emissions
Stage-4 Sol.Recovery
Hydrogen Evaporation Loss
Stage V
Palladium Carbon Organic Residue
Ethyl Acetate Process Emissions
Fenoterol
Hydrogen Bromide in Acetic Sol.Recovery
Stage VI
Acid (33%) Evaporation Loss
Isopropyl Alcohol Organic Residue
Fenoterol Hydrobromide
30
ANNEXURE - VI
Description :
Stage-1 : 2,6-Dimethyl Aniline react with Thiophosgene in presence of Sodium Carbonate in Chloroform solvent
media to get 2,6-Dimethyl phenyl isothiocyanate.
Stage-2 : 2,6-Dimethyl phenyl isothiocyanate is reacted with 3-Amino propanol in presence of Toluene we get
Phenyl thiourea compound and reacted with concentrated Sulfuric acid and Sodium Carbonate to get Xylazine
Base.
Stage-3 : Xylazine Base purified in Isopropyl Alcohol and react with Hydrogen Chloride in Isopropyl Alcohol
(20%) to get Xylazine Hydrochloride.
Flow Chart
2,6-Dimethyl Aniline Sol.Recovery
Thiophosgene Evaporation Loss
Chloroform Stage I Effluent
Sodium Carbonate (10%) Organic Residue
DM Water Process Emissions
Stage-1
3-Amino Propanol Sol.Recovery
Sufluric Acid Evaporation Loss
Toluene Stage II Effluent
Sodium Carbonate (10%) Organic Residue
DM Water Spent Carbon
Carbon Process Emissions
Xylazine Sol.Recovery
Isopropyl Alcohol Evaporation Loss
Hydrochloride (20%) Stage III
Organic Residue
Isopropyl Alcohol Process Emissions
Xylazine Hydrochloride
31
ANNEXURE - VI
Description :
Stage-1 : 2-Acetyl Thiophene is reacted with Paraformaldehyde and Dimethylamine Hydrochloride in presence of
Acetone and Hydrochloric acid to get 3-Dimethylamino-1-thiophen-2-yl propan-1-one Hydrochloride.
Stage-5 : R,S-Duloxetine resoluted with Di-P-Tolyl-L-Tartaric Acid in presence of Methanol and Acetone to get S-
Duloxetine DPTTA Salt.
Stage-6 : S-Duloxetine DPTTA Salt Resolution with Sodium Hydroxide in presence of Methylene Dichloride to get
S-Duloxetine this is further treated with Isopropyl Alcohol Hydrochloride (20%) in presence of Acetone to get
Duloxetine Hydrochloride.
32
ANNEXURE - VI
Flow Chart
2-Acetyl Thiophene
Acetone Sol.Recovery
Dimethylamine Hydrochloride Stage I Evaporation Loss
Paraformaldehyde Aqueous Send to Auth. Party
Hydrochloric Acid (36%) Organic Residue
Stage-1
Methanol
Sodium Hydroxide Sol.Recovery
Sodium Borohydride Stage II Evaporation Loss
Methylene Dichloride Effluent
n-Hexane Organic Residue
DM Water
Stage-2
Dimethyl Sulfoxide
Potassium Hydroxide
18-Crown-6 Sol.Recovery
1-Fluoro naphthalene Evaporation Loss
Stage III
Toluene Effluent
Oxalic Acid Organic Residue
Sodium Hydroxide
Ethyl Acetate
DM Water
Stage-3
Diisopropyl ether
Toluene
Phenyl Chloroformate Sol.Recovery
Hydrochloric Acid (10%) Evaporation Loss
Stage IV
Sodium Bicarbonate (50%) Effluent
Potassium Hydroxide Organic Residue
Dimethyl Sulfoxide Process Emissions
Ethyl Acetate
Water
33
ANNEXURE - VI
Flow Chart
R,S-Duloxetine
Di-P-Tolyl-L-Tartaric Acid Sol.Recovery
Stage V
Methanol Evaporation Loss
Acetone Organic Residue
Duloxetine Hydrochloride
34
ANNEXURE - VI
Description :
Stage-1 : Methyl(R)-3-hydroxy butyrate is treated with p-Toluene sulfonyl chloride in presence of Pyridine
solvent media to get 3-(Toluene-4-sulfonyloxy) butyric acid methyl ester.
Stage-2 : 3-(Toluene-4-sulfonyloxy) butyric acid methyl ester is made to react with 2-Thiophene thiolithium in
presence of Tetrahydrofuran to get 3-(Thiophen-2-ylsulfanyl) butyric acid methyl ester.
Stage-3 : 3-(Thiophen-2-ylsulfanyl) butyric acid methyl ester is heated with Hydrochloric acid in presence of
Toluene solvent media to get 3-(Thiophen-2-ylsulfanyl) butyric acid.
Stage-4 : 3-(Thiophen-2-ylsulfanyl) butyric acid made to react with Trifluoro Acetic Anhydride in presence of
Toluene solvent media to get 6-Methyl-5,6-dihydro thieno[2,3-b]thiopyran-4-one.
Stage-12 : Dorzolamide Base was treated with Maleic acid in presence of Acetone solvent media to get
Dorzolamide Maleate.
Stage-13 : Dorzolamide Maleate is treated with Sodium Bicarbonate in presence of Ethyl Acetate solvent
media to get pure Dorzolamide this is further treated with Isopropyl Alcohol Hydrochloride (20%) to get
Dorzolamide Hydrochloride.
35
ANNEXURE - VI
Flow Chart
P-Toluene Sulfonyl Chloride Sol.Recovery
Evaporation Loss
Methyl ( R )-3-hydroxy butyrate
Stage I Effluent
Pyridine Organic Residue
Water Process Emissions
Stage-1
2-Thiophene thiolithium Sol.Recovery
Sodium Chloride Stage II Evaporation Loss
Tetrahydrofuran Effluent
Water Organic Residue
Stage-2 Sol.Recovery
Toluene Evaporation Loss
Hydrochloric Acid (36%) Stage III Effluent
Water Organic Residue
Process Emissions
Stage-3 Sol.Recovery
Trifluoro Acetic Anhydride Evaporation Loss
Stage IV
Toluene Effluent
Water Organic Residue
Stage-4
Lithium Aluminum Hydride in Sol.Recovery
Tetrahydrofuran (60%) Stage V Evaporation Loss
Toluene Effluent
Water Organic Residue
36
ANNEXURE - VI
Flow Chart
Stage-5
Sulfuric Acid Stage VI Effluent
Water
Stage-6
Hydrogen Peroxide (50%) Sol.Recovery
Ethyl Acetate Stage VII Evaporation Loss
Catalyst Effluent
Water Organic Residue
Stage-7
Acetic Anhydride
Pyridine Sol.Recovery
Acetonitrile StageVIII Evaporation Loss
Tetrahydrofuran Effluent
Sulfuric Acid Organic Residue
Water
Stage-8 Sol.Recovery
Chlorosulfonic Acid Evaporation Loss
Stage IX
Thionyl Chloride Organic Residue
Ethylene Dichloride Process Emissions
Stage-9 Sol.Recovery
Ammonium Hydroxide (26%) Evaporation Loss
Stage X
Tetrahydrofuran Effluent
Water Organic Residue
37
ANNEXURE - VI
Flow Chart
Stage-10 Sol.Recovery
Borane Dimethyl Sulfide Evaporation Loss
Tetrahydrofuran Stage XI Effluent
Sodium Hydroxide Organic Residue
DM Water Process Emissions
Dorzolamide Sol.Recovery
Maleic Acid Stage XII Evaporation Loss
Acetone Organic Residue
Dorzolamide Maleate
Ethyl Acetate Sol.Recovery
Sodium Bicarbonate Evaporation Loss
DM water StageXIII Effluent
Isopropyl Alcohol Organic Residue
Hydrochloride (20%) Process Emissions
Sodium Sulfate
Dorzolamide Hydrochloride
38
ANNEXURE - VI
Description :
Stage-1 : Cyclopentadiene is reacted with Methyl vinyl ketone in presence of Sodium Methoxide in Methanol
solvent media to get 1-Bicyclo[2.2.1]hept-5-en-2-yl ethanone.
Stage-2 : 1-Bicyclo[2.2.1]hept-5-en-2-yl ethanone is react with Piperidine Hydrochloride and Paraformaldehyde
in presence of Sodium Hydroxide in Isopropyl Alcohol solvent media to get 1-Bicyclo[2.2.1]hept-5-en-2-yl-3-
piperidin-1-yl-propan-1-one.
Stage-3 : 1-Bicyclo[2.2.1]hept-5-en-2-yl-3-piperidin-1-yl-propan-1-one is treated with Phenyl Magnesiumchloride
in presence of Tetrahdyrofuran and 1,4-Dioxane solvent media to get Biperiden.
Stage-4 : Biperiden is treated with Hydrochloric acid in presence of Isopropyl Alcohol solvent media to get
Biperiden Hydrochloride.
Flow Chart
Cyclopentadiene
Methyl vinyl ketone Sol.Recovery
Stage I
Sodium Methoxide Evaporation Loss
Methanol Organic Residue
Stage-1
Piperidine Hydrochloride Sol.Recovery
Sodium Hydroxide Evaporation Loss
Stage II
Paraformaldehyde Effluent
Isopropyl Alcohol Organic Residue
Water
Stage-2
Phenyl maganesium chloride Sol.Recovery
1,4-Dioxane Evaporation Loss
Stage III
Tetrahydrofuran Effluent
Hydrochloric Acid (18%) Organic Residue
Water
Biperiden Sol.Recovery
Isopropyl Alcohol Evaporation Loss
Isopropyl Alcohol Stage IV
Organic Residue
Hydrochloride (20%) Process Emissions
Biperiden Hydrochloride
39
ANNEXURE - VI
PRODUCT : Modafinil
Description :
Stage-1 : Thiourea dissolve in 48% Hydrobromic acid and reacted with Benzhydrol and Chloroacetic acid in
presence of Sodium Hydroxide in Ethylene Dichloride solvent media to get Benzhydrylsulfanyl acetic acid.
Stage-2 : Benzhydrylsulfanyl acetic acid treated with Thionyl Chloride in presence of Toluene solvent media to
get Benzhydrylsulfanyl acetyl chloride.
Stage-3 : Benzhydrylsulfanyl acetyl chloride treated with Ammonium Hydroxide to get 2-Benzhydrylsulfanyl
acetamide.
Stage-4 : 2-Benzhydrylsulfanyl acetamide treated with Hydrogen Peroxide in presence of Acetic acid solvent
media to get Modafinil.
Flow Chart
Benzhydrol
Thio Urea
Hydrobromic Acid (48%) Sol.Recovery
Ethylene Dichloride Stage I Evaporation Loss
Sodium Hydroxide Effluent
Chloroacetic Acid Organic Residue
Water
Stage-1 Sol.Recovery
Thionyl Chloride Evaporation Loss
Stage II
Toluene Organic Residue
Process Emissions
Stage-2
Ammonium Hydroxide (26%) Stage III Effluent
Water
Stage-3
Hydrogen Peroxide (50%) Sol.Recovery
Stage IV
Acetic Acid Evaporation Loss
Water Effluent
Modafinil
40
ANNEXURE - VI
PRODUCT : Ledipasvir
Description :
Stage-2 : To a solution of Stage-1 Compound in Acetonitrile at 65°C, charged Hydrochloric acid solution, the reaction
mixture was stirred for 2 hours at 65°C, reaction completion was monitored, after reaction completion, cooled to 40-
45°C, Acetonitrile was added, the resulting slurry was cooled to ambient temperature and filtered, dried to get Stage-2
Intermediate.
Stage-3 : Stage-2 Intermediate reacted with 2-((Methoxy carbonyl) amino)-3-methyl butanoic acid in presence of 1-Ethyl-
3-(3-dimethylaminopropyl)carbodiimide,Diisopropylethylamine and Sodium Bicarbonate using Butyl Alcohol,
Dimethylformamide and Ethyl Acetate as solvent media to obtain Ledipasvir.
41
ANNEXURE - VI
PRODUCT : Ledipasvir
Flow Chart
(1R,3S,4S)-3-(6-Bromo-1H-
benzimidazol-2-yl)-2-azabicyclo
[2.2.1]heptane-2-carboxylic acid-1,1-
dimethylethyl ester
6-{5-(7-Bromo-9,9-difluoro-9H-
fluoren-2-yl)-1H-imidazol-2-yl]-5-aza-
spiro[2,4]heptane-5-carboxylic acid
tert-butyl ester Sol.Recovery
Potassium Propionate Evaporation Loss
Hydrogen Stage I Effluent
Bis(pinacolato)diboron Organic Residue
Dichlorobis(di-tert-butylphenyl Process Emissions
phosphine)palladium(II)
Isopropyl Acetate
N-Acetyl-L-cystine
Tripotassium Phosphate (20%)
Oxalic acid
Sodium Hydroxide
Water
Stage-1 Sol.Recovery
Acetonitrile Evaporation Loss
Stage II
Hydrochloric acid (4%) Effluent
Process Emissions
Stage-2
Dimethylformamide
1-Ethyl-3-(3-dimethylaminopropyl)
carbodiimide
Butyl Alcohol Sol.Recovery
2-((Methoxy carbonyl) amino)-3- Evaporation Loss
methyl butanoic acid Stage III
Effluent
Diisopropylethylamine Organic Residue
Ethyl Acetate Inorgainc Solid Waste
Sodium Bicarbonate
Hyflo
Water
Ledipasvir
42
ANNEXURE - VI
PRODUCT : Pirfenidone
Description :
Flow Chart
Bromobenzene
5-Methyl-1H-pyridin-2-one
Potassium Carbonate Sol.Recovery
Copper Oxide Evaporation Loss
Dimethylformamide Effluent
Stage I
Toluene Organic Residue
Hexane Inorgainc Solid Waste
Sodium Hydroxide Process Emissions
Hydrochloric acid (35%)
Water
Pirfenidone
43
ANNEXURE - VI
Description :
Flow Chart
4-Amino-N-((2S,3S)-3-amino-2-
hydroxy-4-phenylbutyl)-N-
isobutylbenzenesulfonamide
(3R,3aS,6aR)-Hexahydrofuro
[2,3-b]furan-3-yl (4-nitrophenyl) Sol.Recovery
carbonate Evaporation Loss
Stage I
N-Methyl-2-Pyrrolidinone Effluent
Sodium Carbonate Organic Residue
Sodium Chloride
Ethyl Acetate
Ethanol
Water
Darunavir Ethanolate
44
ANNEXURE - VI
PRODUCT : Sofosbuvir
Description :
Flow Chart
2'-Deoxy-2'-fluoro-2'-C-
methyluridine
Propan-2-yl(2S)-2-{[(pentafluoro
phenoxy)(phenoxy)phosphoryl]
amino}propanoate Sol.Recovery
Tetrahydrofuran Evaporation Loss
Sodium Bicarbonate Stage I Effluent
Methylene Dichloride Organic Residue
Hydrochloric acid (35%) Inorgainc Solid Waste
tert-Butylmagnesium Chloride Process Emissions
(20%) in Tetrahydrofuran
Hyflo
Water
Sofosbuvir
45
ANNEXURE - VI
Description :
Stage-2 : Imatinib reacts with Methanesulfonic acid in presence of Acetone, after completion of the reaction,
the resulting product is subjected to filtration and washing using Acetone to form the Imatinib Mesylate as a
white solid.
Flow Chart
6-Methyl-N1-(4-(pyridin-3-yl)
pyrimidin-2-yl)benzene-1,3-
diamine
4-((4-Methylpiperazin-1-yl)
methyl) benzoyl chloride Sol.Recovery
Dihydrochloride Evaporation Loss
Stage I
N-Methylmorpholine Effluent
Methylene Dichloride Organic Residue
Dimethylformamide
Acetonitrile
Sodium Hydroxide
Water
Imatinib Sol.Recovery
Methanesulfonic acid Stage II Evaporation Loss
Acetone Organic Residue
Imatinib Mesylate
46
ANNEXURE - VI
PRODUCT : Gefitinib
Description :
Flow Chart
4-Chloro-6-(3-chloropropoxy)-7-
methoxyquinazoline Sol.Recovery
Morpholine Evaporation Loss
Dimethylformamide Stage I Effluent
Methylene Dichloride Organic Residue
Sodium Sulfate Inorgainc Solid Waste
Water
Stage-1 Sol.Recovery
3-Chloro-4-fluoroaniline Evaporation Loss
Methanol Stage II Effluent
Hydrochloric acid (35%) Organic Residue
Process Emissions
Gefitinib
47
ANNEXURE - VI
PRODUCT : Erlotinib
Description :
Stage-1 : 6,7-Bis(2-methoxy ethoxy) quinazoline, Methylene Dichloride and Dimethylformamide are taken in
0
round bottom flask and start stirring, to the content added Oxalyl Chloride at 25-30 C slowly for 30 minutes,
heated to reflux temperature for 1 hour 30 minutes and cooled to room temperature then washed with 8%
Sodium Bicarbonate solution and the resulting organic layer is washed with water and dried the organic layer
using Sodium Sulfate and distilled the solvent under vacuum at 55-600C. To the residue added n-Heptane and
stirred for 1 hour at 25-300C, filtered the material and washed with n-Heptane to get Stage-1 Compound.
Stage-2 : Stage-1 Compound and Isopropyl Alcohol are added to 3-Ethynylaniline at 25-300C. Under stirring,
the contents are heated to reflux and then refluxed for 1 hour 30 minutes to 2 hours. The reaction mass is
cooled to 25-300C and stirred for 30 minutes. Filtered the material, washed with chilled Isopropyl Alcohol
followed by n-heptane and dried the material at 50-600C to form Erlotinib.
Flow Chart
6,7-Bis(2-methoxy ethoxy)
quinazoline
Oxalyl Chloride Sol.Recovery
Dimethylformamide Evaporation Loss
Methylene Dichloride Stage I Effluent
Sodium Sulfate Organic Residue
Sodium Carbonate Inorgainc Solid Waste
n-Heptane Process Emissions
Water
Stage-1
3-Ethynylaniline Sol.Recovery
Stage II
Isopropyl Alcohol Evaporation Loss
n-Heptane Organic Residue
Erlotinib
48
ANNEXURE - VI
PRODUCT : Dasatinib
Description :
Flow Chart
2-((6-Chloro-2-methylpyrimidin-4-
yl)amino)-N-(2-chloro-6-methyl
phenyl)thiazole-5-carboxamide Sol.Recovery
1-(-2-Hydroxyethyl) piperazine Evaporation Loss
Stage I
Triethylamine Effluent
Tetrabutylammonium Bromide Organic Residue
Acetonitrile
Water
Dasatinib
49
ANNEXURE - VI
Description :
Stage-1 : The tert-Butyl-2-((2S,3R)-3-((tert-Butoxycarbonyl)amino)-2-hydroxy-4-phenylbutyl)-2-(4-(pyridin-2-
yl)benzyl)hydrazine carboxylate is suspended in Methylene Dichloride. Concentrated Hydrochloric acid is added at a
0
sufficiently slow rate to maintain the temperature of the reaction below 30 C. The resulting biphasic mixture is
0
heated at 30-40 C until the two BOC groups have been cleaved. The aqueous solution of the resulting
trihydrochloride salt is added to a buffered solution of the active esters generated from (R)-2-((Methoxycarbonyl)
amino)-3,3-dimethylbutanoic acid and N-Ethyl-N'-dimethyl aminopropyl carbodiimide in Methylene Dichloride. The
0
mixture is stirred at 30-40 C until the coupling reaction is deemed complete by HPLC. The resulting free base is
washed sequentially with 1M Sodium Dihydrogen Phosphate, 0.5 Dipotassium Phosphate and 10% brine. The
0
resulting solution is polished filtered at 40-50 C. Crystallisation of the bisulfate salt was performed by the addition of
10% of the sulfuric acid charge, seeding followed by the addition of the remainder of the acid charge after according
to five progressively faster flow rates, as calculated by an empirically derived cubic equation over approximately
0
5hrs. The product slurry is cooled to 20-25 C over 1hr and held in this temperature range for at least 1hr. Isolation of
product is carried out on a centrifuge. After Methylene Dichloride wash to remove N-Methyl Pyrrolidone, the product
is dried to get Atazanavir Sulfate.
Flow Chart
tert-Butyl-2-((2S,3R)-3-((tert-
Butoxycarbonyl)amino)-2-
hydroxy-4-phenylbutyl)-2-(4-
(pyridin-2-yl)benzyl)hydrazine
carboxylate
(R)-2-((Methoxycarbonyl)
amino)-3,3-dimethylbutanoic
acid Sol.Recovery
Hydrochloric acid (35%) Evaporation Loss
Dipotassium Phosphate Effluent
Stage I
Methylene Dichloride Organic Residue
N-Ethyl-N'-dimethyl amino Inorgainc Solid Waste
propyl carbodiimide Spent Carbon
1-Hydroxybenzotriazole Process Emissions
Sodium Dihydrogen Phosphate
Sodium Hydroxide
Sulfuric acid
N-Methyl Pyrrolidone
Sodium Chloride
Water
Atazanavir Sulfate
50
ANNEXURE - VI
PRODUCT : Pomalidomide
Description :
Stage-1 : Stirred mixture of 3-Nitrobenzene-1,2-dicarboxylic acid with Acetic Anhydride and Acetic acid at
elevated temperature till completion of reaction and reaction mixture cooled to room temperature. Water was
added to isolate the solid. Solid was collected by filtration and dried to obtained the Stage-1 Compound.
Stage-2 : Stage-1 Compound and 3-Aminopiperidine-2,6-dione Hydrochloride was charged to Acetic acid.
Resulting mixture was stirred at elevated temperature till completion of reaction. Cool the reaction mass to room
temperature. Charged Methylene Dichloride and water. The product is extracted in Methylene Dichloride. The
solvent is evaporated and crude product is isolated in water. Further the crude product is purified in Acetone to
obtained the Stage-2 Intermediate.
Stage-3 : Stirred the mixture of Stage-2 Intermediate, Palladium Carbon and Ethyl Acetate till completion of
reaction. Then Palladium Carbon was filtered off and solvent was distilled out to get the crude Pomalidomide
which was purified in Ethanol to gave pure Pomalidomide.
Flow Chart
3-Nitrobenzene-1,2-dicarboxylic
acid Sol.Recovery
Acetic acid Stage I Evaporation Loss
Acetic Anhydride Effluent
Water
Stage-1
3-Aminopiperidine-2,6-dione
Hydrochloride Sol.Recovery
Triethylamine Evaporation Loss
Stage II
Acetic acid Effluent
Methylene Dichloride Organic Residue
Acetone
Water
Stage-2 Sol.Recovery
Palladium Carbon Evaporation Loss
Ethyl Acetate Stage III Effluent
Ethanol Organic Residue
Hydrogen Process Emissions
Pomalidomide
51
ANNEXURE - VI
PRODUCT : Lenalidomide
Description :
Stage-2 : Stirred the mixture of Stage-1 Compound, Palladium Carbon and Ethyl Acetate in presence of
Hydrogen atmosphere till completion of reaction. Then Palladium Carbon was filtered off and solvent was
distilled out to get the crude Lenalidomide, which was purified in Ethanol obtain Pure Lenalidomide.
Flow Chart
2-(Bromomethyl)-3-nitrobenzoic
acid
Aminopiperidine-2,6-dione
Hydrochloride Sol.Recovery
Triethylamine Stage I Evaporation Loss
Acetic acid Effluent
Methylene Dichloride Organic Residue
Acetone
Water
Stage-1 Sol.Recovery
Palladium Carbon Evaporation Loss
Ethyl Acetate Stage II Effluent
Ethanol Organic Residue
Hydrogen Process Emissions
Lenalidomide
52
ANNEXURE - VI
PRODUCT : Latanoprost
Description :
Stage-2 : Stirred the mixture of Stage-1 Compound, water and dilute Hydrochloric acid at ambient temperature
till completion of reaction. Slowly added Sodium Bicarbonate solution to adjust pH to 6.5. Charged Ethyl Acetate
and the product is extracted in Ethyl Acetate. Solvent was distilled out completely and crude product was
purified by column cromatography to obtained Latanoprost.
Flow Chart
[(Z)-7-(1R,2R,3R, 5S)-5-
Hydroxy-2 [(3R)Trimethyl
silyloxy-5-(phenyl-1-pentyl)-3-
trimethyl silyloxy] cyclopentyl-5- Sol.Recovery
hept-enoic acid] Evaporation Loss
Isoproyl Bromide Stage I Effluent
Cesium Carbonate Organic Residue
Dimethylformamide Process Emissions
Ethyl Acetate
Potassium Hydrogen Sulfate
Water
Stage-1 Sol.Recovery
Ethyl Acetate Evaporation Loss
Hydrochloric acid (35%) Stage II Effluent
Sodium Bicarbonate Organic Residue
Water Process Emissions
Latanoprost
53
ANNEXURE - VI
Description :
Flow Chart
(1S)-1-Phenyl-1,2,3,4-
tetrahydroisoquinoline Sol.Recovery
Ethyl Chloroformate Evaporation Loss
Toluene Stage I Effluent
Triethylamine Organic Residue
Hydrochloric acid (35%) Process Emissions
Water
Stage-1
3-Quinuclidinol
Dimethylformamide
Sodium Hydride (60%) in
Paraffin oil Sol.Recovery
Sodium Hydroxide Evaporation Loss
Stage II
Ethyl Acetate Effluent
Toluene Organic Residue
Succinic acid Process Emissions
Ethanol
Sodium Hydroxide (50%)
Water
Solifenacin Succinate
54
ANNEXURE - VI
PRODUCT : Cabazitaxel
Description :
Flow Chart
(2aR,4S,4aS,6R,9S,11S,12S,12
aR,12bS)-12b-acetoxy-9-
(((2R,3S)-3-((tert-butoxy
carbonyl) amino)-3-phenyl-2-
((triethylsilyl)oxy)propanoyl)oxy)-
11-hydroxy-4,6-dimethoxy-
4a,8,13,13-tetramethyl-5-oxo-
2a,3,4,4a,5,6,9,10,11,12,12a,12 Sol.Recovery
b-dodecahydro-1H-7,11- Stage I Evaporation Loss
methanocyclodeca [3,4]benzo Effluent
[1,2-b]oxet-12-yl benzoate Organic Residue
Hydrogen Fluoride
Pyridine
Acetonitrile
Methylene Dichloride
Methanol
Water
Cabazitaxel
55
ANNEXURE - VI
PRODUCT : Entecavir
Description :
Flow Chart
6-(Benzyloxy)-9-((1S,3R,4S)-4-
(benzyloxy)-3-((benzyloxy)
methyl)-2-methylenecyclopentyl)- Sol.Recovery
9H-purin-2-amine Evaporation Loss
Stage I
Hydrogen Organic Residue
Palladium Carbon Process Emissions
Methanol
Acetone
Entecavir
56
ANNEXURE - VI
PRODUCT : Perampanel
Description :
Flow Chart
2,3'-Bipyridin-6'(1'H)-one
Phenylboronic acid
2-(1,3,2-Dioxaborolan-2-yl)
benzonitrile Sol.Recovery
Copper Acetate Evaporation Loss
N-Bromo Succinimide Effluent
Stage I
Triphenylphosphine Organic Residue
Palladium Acetate Inorgainc Solid Waste
Copper Iodide Process Emissions
Methylene Dichloride
Toluene
Water
Perampanel
57
ANNEXURE - VI
PRODUCT : 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-
methyltetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
Description :
Stage-1 : ((2R,3R,4R)-3-(benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate is treated with
Vitride solution in Toluene in presence of solvent Toluene, after completion of reaction, pH is adjusted to 2.0-3.0
by adding dilute Hydrochloric acid solution in the reaction mass, layer was separated, further water and Sodium
Chloride wash is given to the reaction mass. Distilled out Toluene from the reaction mass below 65°C to get
concentrated syrupy mass is identified as Stage-1 Compound.
Stage-2 : Stage-1 Compound is dissolved in solvent Methylene Dichloride in which Triethylamine is added,
further Sulfuryl Chloride is added at elevated temperature, after completion of reaction, water added in the
reaction mass, layer was separated, further Citric acid solution andPotassium Hydroxide solution wash is given to
the reaction mass and layer was separated. Distilled out Methylene Dichloride from the reaction mass below 40°C
to get concentrated syrupy mass is identified as Stage-2 Intermediate.
Stage-3 : N-(2-Oxo-1,2-dihydropyrimidin-4-yl)benzamide, Hexamethyldisilazane and Ammonium Sulfate is reflux
in the presence of solvent Chlorobenzene. After completion of clear solution, distilled out Chlorobenzene under
vacuum below 120°C, further cool the reaction mass and dissolve the concentrated syrupy mass in the solvent
Methylene Dichloride. In this solution Stage-2 Intermediate is added at 25-35°C, after completion of addition, Tin
Chloride is added further reaction is reflux at 60-70°C for 12 hrs, cool the reaction mass to 25-35°C. Dilute the
reaction mass with Methylene Dichloride and charge NaHCO3 solution and hyflow filter the reaction mass. Again
and charge Sodium Bicarbonate solution and separate the layer. Distilled out Methylene Dichloride from the
reaction mass below 40°C to get concentrated syrupy mass and product was isolated in Isopropyl Alcohol to give
Stage-3 Compound.
Stage-4 : Stage-3 Compound is hydrolysed with water in acidic medium by using Acetic acid at the elevated
temperature 100-105°C for 3-4 hrs, which is further diluted by adding water at ambient temperature and filter the
product which is identified as Stage-4 Intermediate.
Stage-5 : Stage-4 Intermediate is treated with Ammonia in the presence of solvent Methanol at elevated
temperature 10-20°C, after completion of reaction, on filtration Methanol is distilled out under vacuum below 60-
65°C to get concentrate mass. In this mass Ethyl Acetate added and distilled out to remove traces of Methanol
and Ethyl Acetate and the product was isolated in Ethyl Acetate to obtain 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-
(hydroxymethyl)-3-methyltetrahydrofuran-2-yl) pyrimidine-2,4(1H,3H)-dione.
58
ANNEXURE - VI
PRODUCT : 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-
methyltetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
Flow Chart
((2R,3R,4R)-3-(Benzoyloxy)-4-
fluoro-4-methyl-5-oxotetra
hydrofuran-2-yl)methyl Sol.Recovery
benzoate Evaporation Loss
Vitride (70%) in Toluene Stage I Effluent
Toluene Organic Residue
Sodium Chloride Process Emissions
Hydrochloric acid (35%)
Water
Stage-1
Sulfuryl Chloride Sol.Recovery
Triethylamine Evaporation Loss
Stage II
Methylene Dichloride Effluent
Citric acid (15%) Organic Residue
Potassium Hydroxide (7%)
Stage-2
N-(2-Oxo-1,2-dihydropyrimidin-
4-yl)benzamide
Chlorobenzene Sol.Recovery
Hexamethyldisilazane Evaporation Loss
Stage III
Ammonium Sulfate Effluent
Tin Chloride Organic Residue
Methylene Dichloride Process Emissions
Isopropyl Alcohol
Sodium Bicarbonate (5%)
Stage-3 Sol.Recovery
Acetic acid Stage IV Evaporation Loss
Water Effluent
Stage-4 Sol.Recovery
Methanol Evaporation Loss
Stage V
Ammonia (20%) Effluent
Ethyl Acetate Organic Residue
1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidine-
2,4(1H,3H)-dione
59
ANNEXURE - VI
PRODUCT : (S)-Isopropyl-2-(((R)-(perfluorophenoxy)(phenoxy)
phosphoryl)amino)propanoate
Description :
Stage-1 : Phenyl Phosphorodichloridate is treated with (S)-Isopropyl-2-aminopropanoate Hydrochloride in the
presence of alkaline medium by using Triethylamine in the solvent Methylene Dichloride at the elevated temperature
after completion of reaction, mixture of 2,3,4,5,6-Pentafluorophenol, Triethylamine in Methylene Dichloride is added
at the elevated temperature after completion of reaction, filter the reaction mass to remove Triethylamine salt.
Filtrate is distilled out under vacuum below 35°C further Hexane is added and distilled out to remove traces of
Methylene Dichloride. After completion of distillation, the product was isolated in Hexane and Methyl tert-Butyl ether
and to obtain crude (S)-Isopropyl-2-(((R)-(perfluoro phenoxy)(phenoxy)phosphoryl) amino)propanoate. This Crude is
dissolved in Ethyl Acetate, water and brine wash is given further Ethyl Acetate is distilled out under vacuum below
35°C further Hexane is added and distilled out to remove traces of Ethyl Acetate. After completion of distillation, the
product was isolated in Hexane and Methyl tert-Butyl ether and to obtain pure (S)-Isopropyl-2-(((R)-(perfluoro
phenoxy)(phenoxy)phosphoryl) amino)propanoate.
Flow Chart
Phenyl Phosphodichloridate
(S)-Isopropyl-2-aminopropanoate
Hydrochloride
2,3,4,5,6-Pentafluorophenol
Methylene Dichloride Sol.Recovery
Triethylamine Stage I Evaporation Loss
Hexane Effluent
Methyl tert-Butyl ether Organic Residue
Ethyl Acetate
Sodium Chloride
Water
(S)-Isopropyl-2-(((R)-(perfluorophenoxy)(phenoxy)phosphoryl)amino)propanoate
60
ANNEXURE - VI
Description :
61
ANNEXURE - VI
Flow Chart
1,1'-([1,1'-Biphenyl]-4,4'-diyl)
diethanone Sol.Recovery
Bromine Stage I Evaporation Loss
Methylene Dichloride Organic Residue
Tetrahydrofuran Process Emissions
Stage-1
BOC-L-Proline
Diisopropylethylamine
Acetonitrile Sol.Recovery
Ammonium Acetate Evaporation Loss
Acetic acid Stage II Effluent
Ethyl Acetate Organic Residue
Toluene Process Emissions
Methanol
N-Methyl Pyrrolidone
Water
Stage-2 Sol.Recovery
Hydrochloric acid (35%) Evaporation Loss
Isopropyl Alcohol Stage III Effluent
Methanol Organic Residue
Water Process Emissions
Stage-3
N-(Methoxycarbonyl)-L-valine
Hydroxybenzotriazole
1-Ethyl-3-(3-dimethylaminopropyl)
carbodiimide Hydrochloride
Methylene Dichloride Sol.Recovery
Triethylamine Evaporation Loss
Isopropyl Alcohol Hydrochloride Stage IV Effluent
(15%) Organic Residue
Dimethyl Sulfoxide Process Emissions
Methanol
Sodium Bicarbonate
Ethanol
Isopropyl Alcohol
Water
Daclatasvir Dihydrochloride
62
ANNEXURE - VI
PRODUCT : Rifaximin
Description :
Stage-1 : Rifamycin-O on reaction with 2-Amino-4-methylpyridine in presence of Iodine and Ascorbic acid in
Ethanol and water. After completion of the reaction, the reaction mass was cooled and filtered to get the crude
material. Crude material further purification in Ethanol and water to obtain pure Rifaximin as red colour powder.
Flow Chart
Rifamycin-O
2-Amino-4-methylpyridine
Acetic acid Sol.Recovery
Ascorbic acid Evaporation Loss
Stage I
Hydrochloric acid (35%) Effluent
Ethanol Organic Residue
Iodine Inorgainc Solid Waste
Water
Rifaximin
63
ANNEXURE - VI
PRODUCT : Linezolid
Description :
Stage-2 : Reaction of Stage-1 Compound with Monomethylamine in Water and Methanol, after completion of
reaction product was partitioned between water and Methylene Dichloride, washed with Hydrochloric acid. To the
Methylene Dichloride layer Acetic Anhydride was added. After completion of the reaction, reaction mass was
washed with water and solvent was evaporated under reduced pressure to get crude material. Isolation of
Linezolid frm Toluene to form Pure Linezolid.
Flow Chart
2-[(2S)-Oxiran-2-yl-methyl]-1H-
isoindole-1,3(2H)-dione
Methyl-[3-fluoro-4-(morpholin-4-
yl)phenyl]carbamate Sol.Recovery
Stage I
Triethylamine Evaporation Loss
Dimethylformamide Organic Residue
Ethyl Acetate
Methanol
Stage-1
Monomethylamine (40%)
Acetic Anhydride Sol.Recovery
Methylene Dichloride Stage II Evaporation Loss
Hydrochloric acid (35%) Effluent
Ammonia (25%) Organic Residue
Water
Linezolid
64
ANNEXURE - VI
Description :
Stage-2 : Stage-1 Compound is reacted with dilute Hydrochloric acid in presence of Methanol and Toluene. After
completion of reaction, the reaction mass was treated with Sodium Hydroxide solution and washed with Methyl
tert-Butyl ether. Finally the reaction mass is treated with Calcium Acetate to obtain Rosuvastatin Calcium.
Flow Chart
N-[5-(Bromomethyl)-4-(-4-
Fluorophenyl)-6-propan-2-yl)
pyrimidin-2-yl]-N-methyl
methanesulfonamide
phosphonium salt Sol.Recovery
tert-Butyl-[(4R,6S)-6-formyl-2,2- Evaporation Loss
dimethyl-1,3-dioxan-4-yl] Stage I Effluent
acetate Organic Residue
Potassium Carbonate Process Emissions
Dimethyl Sulfoxide
Toluene
Methanol
Water
Stage-1
Methanol
Toluene Sol.Recovery
Sodium Hydroxide Evaporation Loss
Stage II
Calcium Acetate Effluent
Methyl tert-Butyl ether Organic Residue
Hydrochloric acid (35%)
Water
Rosuvastatin Calcium
65
ANNEXURE - VI
PRODUCT : Pregabalin
Description :
Stage-1 : Hydrolysis of Diethyl-(1-cyano-3-methylbutyl) propanedioate with Potassium Hydroxide gives Potassium 3-
Cyano-5-methyl hexanoate, which in-situ reduced by using Raney Nickel as catalyst in presence of Acetic acid in
Methanol solvent medium to give Stage-1 Compound.
Stage-2 : Racemic Stage-1 Compound is then subjected to resolution by using S(+) Mandelic acid as resolving agent
in mixture of Isopropyl Alcohol and Water to form optically pure [S(+)-3-(Amino methyl)-5-methylhexanoic acid
Mandelic acid salt as Stage-2 material.
Stage-3 : Stage-2 material is on basic and acidic treatment with Sodium Hydroxide and Hydrochloric acid gives crude
Pregabalin. It is recrystallised in aqueous medium by conventional manner to obtain Pure Pregabalin.
Flow Chart
Diethyl-(1-cyano-3-methylbutyl)
propanedioate
Potassium Hydroxide Sol.Recovery
Methanol Evaporation Loss
Stage I
Raney Nickel Effluent
Hydrogen Organic Residue
Acetic acid Process Emissions
Water
Stage-1 Sol.Recovery
S(+) Mandelic acid Evaporation Loss
Stage II
Isopropyl Alcohol Effluent
Water Organic Residue
Stage-2
Sodium Hydroxide
Stage III Effluent
Hydrochloric acid (35%)
Water
Pregabalin
66
ANNEXURE - VI
PRODUCT : Flurbiprofen
Description :
Flow Chart
2,4-Difluoronitrobenzene
Diethyl methylmalonate
Sodium Hydroxide Sol.Recovery
Dimethylformamide Evaporation Loss
Methanol Stage I Effluent
Toluene Organic Residue
Palladium Carbon Process Emissions
Hydrogen
Water
Stage-1 Sol.Recovery
Toluene Evaporation Loss
Copper Powder Effluent
Stage II
Trichloroacetic acid Organic Residue
Isopropyl Nitrite Inorgainc Solid Waste
Water Process Emissions
Stage-2 Sol.Recovery
Sodium Hydroxide Evaporation Loss
Acetic acid Stage III Effluent
Toluene Organic Residue
Water Process Emissions
Flurbiprofen
67
ANNEXURE - VI
Description :
Stage-2 : Reduction of Stage-1 Compound with Sodium Borohydride in presence of Trifluoroacetic acid using
Tetrahydrofuran at 0-50C for 3-4 hrs after completion of reaction, reaction mass was quenched with Sodium
Hydroxide and extracted in Ethyl Acetate, and washed Ethyl Acetate layer with water, distilled out Ethyl Acetate
and isolated the compound in water to get Stage-2 Intermediate.
68
ANNEXURE - VI
Flow Chart
1H-Indole-5-carbonitrile
4-Chlorobutyryl Chloride
Aluminium Chloride Sol.Recovery
Methylene Dichloride Evaporation Loss
Stage I
Nitromethane Effluent
Hydrochloric acid (35%) Organic Residue
Methanol Process Emissions
Water
Stage-1
Sodium Borohydride
Tetrahydrofuran Sol.Recovery
Ethyl Acetate Evaporation Loss
Stage II
Trifluoroacetic acid Effluent
Sodium Hydroxide Organic Residue
Isopropyl Alcohol Process Emissions
Water
Ethyl-5-nitro-1-benzofuran-2-
carboxylate Sol.Recovery
Palladium Carbon Evaporation Loss
Ethyl Acetate Hydrochloride Stage III Effluent
(12%) Organic Residue
Hydrogen Process Emissions
Ethyl Acetate
Stage-3
Bis(2-chloroethyl)amine
Hydrochloride
o-Xylene Sol.Recovery
Acetone Evaporation Loss
Methanol Stage IV Effluent
2-(2-Ethoxyethoxy)ethanol Organic Residue
(Carbitol) Process Emissions
Ethyl Acetate
Sodium Carbonate
Water
69
ANNEXURE - VI
Flow Chart
Stage-2
Stage-4
Sodium Iodide Sol.Recovery
Sodium Carbonate Evaporation Loss
N-Methyl Pyrrolidone Stage V Effluent
Hydrochloric acid (35%) Organic Residue
Ethyl Acetate Process Emissions
Acetone
Water
Stage-5
Ammonia (20%)
Methanol Sol.Recovery
Dimethylformamide Stage VI Evaporation Loss
Hydrochloric acid (35%) Effluent
Sodium Hydroxide Organic Residue
Water
Vilazodone Hydrochloride
70
ANNEXURE - VI
Description :
Stage-2 : Stage-1 Compound reacted with Sodium Hydroxide in presence of Methanol and Toluene solvent media, the
resulting solution is subjected to distillation with n-Heptane to obtain Montelukast Sodium.
Flow Chart
(S,E)-1-(3-(2-(7-Chloroquinolin-2-
yl)vinyl)phenyl)-3-(2-(2-hydroxy
propan-2-yl)phenyl)propan-1-ol
Acetonitrile
Toluene
Petroleum Ether
Diisopropylethylamine
Methanesulfonyl Chloride Sol.Recovery
Dimethyl Sulfoxide Stage I Evaporation Loss
Sodium Methoxide (25%) in Effluent
Methanol Organic Residue
2-(1-(Mercaptomethyl)cyclopropyl)
acetic acid
Sodium Hydroxide
tert-Butylamine
Acetic acid
Water
Stage-1
Methanol Sol.Recovery
Sodium Hydroxide Stage II Evaporation Loss
Toluene Effluent
n-Heptane Organic Residue
Montelukast Sodium
71
ANNEXURE - VI
PRODUCT : Teriflunomide
Description :
Stage-1 : 5-Methyl isoxazole-4-carboxylic acid on reaction with Phosphorous Pentachloride to give acid chloride,
resulting acid chloride on reaction with 4-(Trifluoromethyl)aniline in presence of Potassium Bicarbonate using
Methylene Dichloride and Acetone solvent media to form Stage-1 Compound.
Stage-2 : Stage-1 Compound on hydrolysis in presence of Sodium Hydroxide and Hydrochloric acid using
Methanol and Acetone solvent media to obtain Teriflunomide.
Flow Chart
5-Methyl isoxazole-4-carboxylic
acid
4-(Trifluoromethyl)aniline Sol.Recovery
Methylene Dichloride Evaporation Loss
Stage I
Phosphorous Pentachloride Effluent
Acetone Organic Residue
Potassium Bicarbonate Process Emissions
Water
Stage-1
Sodium Hydroxide Sol.Recovery
Hydrochloric acid (35%) Evaporation Loss
Stage II
Methanol Effluent
Acetone Organic Residue
Water
Teriflunomide
72
ANNEXURE - VI
Description :
Flow Chart
17-Iodo androsta-5,16-diene-3- Sol.Recovery
β-ol Evaporation Loss
3-Diethylboropyridine Effluent
Sodium Carbonate (20%) Organic Residue
Bis(Triphenylphosphine)
palladium(II) dichloride Stage I
Tetrahydrofuran
Ethyl Acetate
Toluene
Water Process Emissions
Stage-1 Sol.Recovery
Tetrahydrofuran Evaporation Loss
Triethylamine Effluent
Stage II
Acetyl Chloride Organic Residue
Ethanol
Water
Abiraterone Acetate
73
ANNEXURE - VI
Description :
Flow Chart
Ethyl-3-{[3-amino-4-(methylamino)
benzoyl](pyridin-2-yl)amino}
propanoate Sol.Recovery
Carbonyldiimidazole Evaporation Loss
Toluene Stage I Effluent
[(4-Cyanophenyl)amino]acetic acid Organic Residue
Methylene Dichloride Process Emissions
Ethyl Acetate
Water
Stage-1
Ethanol Sol.Recovery
tert-Butanol Stage II Evaporation Loss
Ammonia (20%) Effluent
Hydrogen Chloride Organic Residue
Stage-2
Potassium Carbonate Sol.Recovery
Acetone Evaporation Loss
Stage III
n-Hexyl Chloroformate Effluent
Ethyl Acetate Organic Residue
Water Process Emissions
Stage-3 Sol.Recovery
Methanesulfonic acid Stage IV Evaporation Loss
Acetone Organic Residue
74
ANNEXURE - VII
PRODUCT : Betahistine
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2-Hydroxy-1-Pyridinyl-3-trichloro Propane = 3.66 244
Ammonium Hydroxide (28%) = 2 133.33
Bromine = 1.76 117.33
Hydrogen = 0.1 6.67
Methanol = 14.1 940
Methanol (90%) = 18.3 1220
Methyl Iodide = 1.5 100
Palladium Carbon = 0.15 10
Potassium Hydroxide = 1.2 80
Sodium Carbonate = 1.12 74.67
Sodium Methoxide = 1.3 86.67
Sulfuric Acid = 0.715 47.67
Toluene = 5 333.33
PRODUCT : Rivastigmine
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
Acetonitrile = 5 500
α−m-Hydroxy phenyl ethyl dimethy amine = 1 100
Diethyl ether = 1 100
N-Ethyl methyl Carbomyl chloride = 0.736 73.6
Sodium Hydride (60%) = 0.243 24.3
75
ANNEXURE - VII
PRODUCT : L-Thyroxine
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2-Acetylamino-3-(4-hydroxy-3,5-diiodo phenyl)
= 1.65 55
propionic acid ethyl ester
Acetic Acid = 0.6 20
Boric Acid = 0.465 15.5
Ethanol = 29.7 990
Hydrochloric Acid (36%) = 0.6 20
Sodium Hydroxide = 0.265 8.83
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
1,4-Dioxane = 14.6 973.33
3,5-Dibenzyloxy Acetophenone = 4 266.67
4-Methoxy phenyl-2-aminopropane = 1.67 111.33
Aluminum Chloride = 0.5 33.33
Ethyl Acetate = 30.85 2056.67
Hydrochloric Acid (36%) = 0.75 50
Hydrogen = 0.06 4
Hydrogen Bromide in Acetic Acid (33%) = 0.712 47.47
Isopropyl Alcohol = 4.4 293.33
Maleic Acid = 0.85 56.67
Methanol = 58.5 3900
Palladium Carbon = 0.015 1
Selenium Dioxide = 1.337 89.13
Sodium Bicarbonate = 1.3 86.67
Sodium Borohydride = 0.3 20
Toluene = 40.5 2700
76
ANNEXURE - VII
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2,6-Dimethyl Aniline = 0.83 83
3-Amino Propanol = 0.5 50
Carbon = 0.1 10
Chloroform = 4.15 415
Isopropyl Alcohol = 2.5 250
Isopropyl Alcohol Hydrochloride (20%) = 1 100
Sodium Carbonate (10%) = 12.5 1250
Sufluric Acid = 0.2 20
Thiophosgene = 0.79 79
Toluene = 10 1000
77
ANNEXURE - VII
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
18-Crown-6 = 0.11 5.5
1-Fluoro naphthalene = 2 100
2-Acetyl Thiophene = 2 100
Acetone = 66.7 3335
Carbon = 0.1 5
Diisopropyl ether = 1.7 85
Dimethyl Sulfoxide = 26.3 1315
Dimethylamine Hydrochloride = 1.5 75
Di-P-Tolyl-L-Tartaric Acid = 3.405 170.25
Ethyl Acetate = 42.75 2137.5
Hydrochloric Acid (10%) = 8.16 408
Hydrochloric Acid (36%) = 1 50
Isopropyl Alcohol Hydrochloride (20%) = 0.9 45
Methanol = 25.84 1292
Methylene Dichloride = 42.45 2122.5
n-Hexane = 4.15 207.5
Oxalic Acid = 1.125 56.25
Paraformaldehyde = 0.5 25
Phenyl Chloroformate = 2 100
Potassium Hydroxide = 2.025 101.25
Sodium Bicarbonate (50%) = 4 200
Sodium Borohydride = 0.5 25
Sodium Hydroxide = 2.535 126.75
Toluene = 39.45 1972.5
78
ANNEXURE - VII
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2-Thiophene thiolithium = 1.48 49.33
Acetic Anhydride = 0.65 21.67
Acetone = 8.85 295
Acetonitrile = 0.254 8.47
Ammonium Hydroxide (26%) = 1.65 55
Borane Dimethyl Sulfide = 0.56 18.67
Catalyst = 0.4 13.33
Chlorosulfonic Acid = 0.62 20.67
Ethyl Acetate = 13.5 450
Ethylene Dichloride = 13.5 450
Hydrochloric Acid (36%) = 1.5 50
Hydrogen Peroxide (50%) = 1.3 43.33
Isopropyl Alcohol Hydrochloride (20%) = 0.7 23.33
Lithium Aluminum Hydride in Tetrahydrofuran (60%) = 0.3 10
Maleic Acid = 0.45 15
Methyl ( R )-3-hydroxy butyrate = 1.61 53.67
p -Toluenesulfonyl Chloride = 2.86 95.33
Pyridine = 8.725 290.83
Sodium Bicarbonate = 0.6 20
Sodium Chloride = 0.875 29.17
Sodium Hydroxide = 0.5 16.67
Sodium Sulfate = 0.14 4.67
Sulfuric Acid = 2.8 93.33
Tetrahydrofuran = 42.05 1401.67
Thionyl Chloride = 0.62 20.67
Toluene = 27.45 915
Trifluoro Acetic Anhydride = 2.2 73.33
79
ANNEXURE - VII
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
1,4-Dioxane = 4.4 440
Cyclopentadiene = 0.35 35
Hydrochloric Acid (18%) = 1 100
Isopropyl Alcohol = 7.1 710
Isopropyl Alcohol Hydrochloride (20%) = 0.75 75
Methanol = 3.5 350
Methyl vinyl ketone = 0.38 38
Paraformaldehyde = 0.15 15
Phenyl maganesium chloride = 0.6 60
Piperidine Hydrochloride = 0.51 51
Sodium Hydroxide = 0.3 30
Sodium Methoxide = 0.01 1
Tetrahydrofuran = 2.64 264
PRODUCT : Modafinil
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
Acetic Acid = 3.15 315
Ammonium Hydroxide (26%) = 2 200
Benzhydrol = 1.25 125
Chloroacetic Acid = 0.75 75
Ethylene Dichloride = 6.25 625
Hydrobromic Acid (48%) = 5 500
Hydrogen Peroxide (50%) = 0.47 47
Sodium Hydroxide = 0.35 35
Thio Urea = 0.625 62.5
Thionyl Chloride = 0.7 70
Toluene = 7.5 750
80
ANNEXURE - VII
PRODUCT : Ledipasvir
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
(1R,3S,4S)-3-(6-Bromo-1H-benzimidazol-2-yl)-2-
azabicyclo [2.2.1]heptane-2-carboxylic acid-1,1- = 83 22.13
dimethylethyl ester
1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide = 364 97.07
2-((Methoxy carbonyl) amino)-3-methyl butanoic acid = 60 16
6-{5-(7-Bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-
imidazol-2-yl]-5-aza-spiro[2,4]heptane-5-carboxylic = 115 30.67
acid tert-butyl ester
Acetonitrile = 1400 373.33
Bis(pinacolato)diboron = 63 16.80
Butyl Alcohol = 1640 437.33
Dichlorobis(di-tert-butylphenylphosphine)
= 7 1.87
palladium(II)
Diisopropylethylamine = 46 12.27
Dimethylformamide = 730 194.67
Ethyl Acetate = 1370 365.33
Hydrochloric acid (4%) = 2786 742.93
Hydrogen = 1 0.27
Hyflo = 27 7.2
Isopropyl Acetate = 830 221.33
N-Acetyl-L-cystine = 20 5.33
Oxalic acid = 30 8
Potassium Propionate = 70 18.67
Sodium Bicarbonate = 91 24.27
Sodium Hydroxide = 40 10.67
Tripotassium Phosphate (20%) = 166 44.27
81
ANNEXURE - VII
PRODUCT : Pirfenidone
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
5-Methyl-1H-pyridin-2-one = 42 42.04
Bromobenzene = 58 58.06
Copper Oxide = 1 1.00
Dimethylformamide = 50 50.05
Hexane = 50 50.05
Hydrochloric acid (35%) = 64 64.06
Potassium Carbonate = 34 34.03
Sodium Hydroxide = 19 19.02
Toluene = 120 120.12
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
(3R,3aS,6aR)-Hexahydrofuro [2,3-b]furan-3-yl (4-
= 56 55.97
nitrophenyl) carbonate
4-Amino-N-((2S,3S)-3-amino-2-hydroxy-4-
= 73 72.96
phenylbutyl)-N-isobutylbenzenesulfonamide
Ethanol = 220 219.89
Ethyl Acetate = 730 729.64
N-Methyl-2-Pyrrolidinone = 150 149.93
Sodium Carbonate = 20 19.99
Sodium Chloride = 11 10.99
82
ANNEXURE - VII
PRODUCT : Sofosbuvir
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2'-Deoxy-2'-fluoro-2'-C-methyluridine = 103 61.68
Hydrochloric acid (35%) = 103 61.68
Hyflo = 9 5.39
Methylene Dichloride = 1030 616.77
Propan-2-yl(2S)-2-{[(pentafluoro phenoxy)
= 216 129.34
(phenoxy)phosphoryl] amino}propanoate
Sodium Bicarbonate = 81 48.50
tert-Butylmagnesium Chloride (20%) in
= 1246 746.11
Tetrahydrofuran
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
4-((4-Methylpiperazin-1-yl) methyl) benzoyl chloride
= 21 20.96
Dihydrochloride
6-Methyl-N1-(4-(pyridin-3-yl) pyrimidin-2-yl)benzene-
= 14 13.97
1,3-diamine
Acetone = 170 169.66
Acetonitrile = 70 69.86
Dimethylformamide = 30 29.94
Methanesulfonic acid = 4 3.99
Methylene Dichloride = 210 209.58
N-Methylmorpholine = 38 37.92
Sodium Hydroxide = 21 20.96
83
ANNEXURE - VII
PRODUCT : Gefitinib
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
3-Chloro-4-fluoroaniline = 9 9.02
4-Chloro-6-(3-chloropropoxy)-7-methoxyquinazoline = 14 14.04
Dimethylformamide = 260 260.65
Hydrochloric acid (35%) = 4 4.01
Methanol = 110 110.28
Methylene Dichloride = 260 260.65
Morpholine = 15 15.04
Sodium Sulfate = 6 6.02
PRODUCT : Erlotinib
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
3-Ethynylaniline = 16 16
6,7-Bis(2-methoxy ethoxy) quinazoline = 24 24
Dimethylformamide = 40 40
Isopropyl Alcohol = 200 200
Methylene Dichloride = 290 290
n-Heptane = 210 210
Oxalyl Chloride = 12 12
Sodium Carbonate = 19 19
Sodium Sulfate = 12 12
84
ANNEXURE - VII
PRODUCT : Dasatinib
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
1-(-2-Hydroxyethyl) piperazine = 4 3.98
2-((6-Chloro-2-methylpyrimidin-4-yl)amino)-N-(2-
= 7 6.97
chloro-6-methyl phenyl)thiazole-5-carboxamide
Acetonitrile = 110 109.45
Tetrabutylammonium Bromide = 7 6.97
Triethylamine = 3 2.99
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
(R)-2-((Methoxycarbonyl) amino)-3,3-
= 55 54.97
dimethylbutanoic acid
1-Hydroxybenzotriazole = 7 7.00
Dipotassium Phosphate = 8 8.00
Hydrochloric acid (35%) = 84 83.96
Methylene Dichloride = 710 709.65
N-Ethyl-N'-dimethyl amino propyl carbodiimide = 19 18.99
N-Methyl Pyrrolidone = 580 579.71
Sodium Chloride = 5 5.00
Sodium Dihydrogen Phosphate = 8 8.00
Sodium Hydroxide = 30 29.99
Sulfuric acid = 15 14.99
tert-Butyl-2-((2S,3R)-3-((tert-Butoxy carbonyl) amino)-
2-hydroxy-4-phenylbutyl)-2-(4-(pyridin-2- = 71 70.96
yl)benzyl)hydrazine carboxylate
85
ANNEXURE - VII
PRODUCT : Pomalidomide
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
3-Aminopiperidine-2,6-dione Hydrochloride = 4 4.00
3-Nitrobenzene-1,2-dicarboxylic acid = 6 6.01
Acetic acid = 6 6.01
Acetic Anhydride = 5 5.01
Acetone = 20 20.02
Ethanol = 30 30.03
Ethyl Acetate = 40 40.04
Hydrogen = 0.5 0.50
Methylene Dichloride = 30 30.03
Palladium Carbon = 1 1.00
Triethylamine = 3 3.00
PRODUCT : Lenalidomide
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2-(Bromomethyl)-3-nitrobenzoic acid = 11 10.95
Acetic acid = 50 49.75
Acetone = 70 69.65
Aminopiperidine-2,6-dione Hydrochloride = 8 7.96
Ethanol = 100 99.50
Ethyl Acetate = 140 139.30
Hydrogen = 1 1.00
Methylene Dichloride = 100 99.50
Palladium Carbon = 1 1.00
Triethylamine = 9 8.96
86
ANNEXURE - VII
PRODUCT : Latanoprost
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
[(Z)-7-(1R,2R,3R, 5S)-5-Hydroxy-2 [(3R)trimethyl
silyloxy-5-(phenyl-1-pentyl)-3-trimethyl silyloxy] = 19 19.08
cyclopentyl-5-hept-enoic acid]
Cesium Carbonate = 15 15.06
Dimethylformamide = 190 190.76
Ethyl Acetate = 400 401.61
Hydrochloric acid (35%) = 3 3.01
Isoproyl Bromide = 7 7.03
Potassium Hydrogen Sulfate = 7 7.03
Sodium Bicarbonate = 2 2.01
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
(1S)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline = 20 19.96
3-Quinuclidinol = 9 8.98
Dimethylformamide = 20 19.96
Ethanol = 23 22.95
Ethyl Acetate = 180 179.64
Ethyl Chloroformate = 11 10.98
Hydrochloric acid (35%) = 4 3.99
Sodium Hydride (60%) in Paraffin oil = 5 4.99
Sodium Hydroxide = 4 3.99
Sodium Hydroxide (50%) = 7 6.99
Succinic acid = 13 12.97
Toluene = 200 199.60
Triethylamine = 11 10.98
87
ANNEXURE - VII
PRODUCT : Cabazitaxel
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-
acetoxy-9-(((2R,3S)-3-((tert-butoxy carbonyl) amino)-
3-phenyl-2-((triethylsilyl)oxy)propanoyl) oxy)-11-
hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-5-oxo- = 5 5.01
2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-
7,11-methanocyclodeca [3,4]benzo [1,2-b]oxet-12-yl
benzoate
Acetonitrile = 50 50.05
Hydrogen Fluoride = 1 1.00
Methanol = 50 50.05
Methylene Dichloride = 50 50.05
Pyridine = 5 5.01
88
ANNEXURE - VII
PRODUCT : Entecavir
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
6-(Benzyloxy)-9-((1S,3R,4S)-4-(benzyloxy)-3-
((benzyloxy) methyl)-2-methylenecyclopentyl)-9H- = 37 36.93
purin-2-amine
Acetone = 370 369.26
Hydrogen = 1 1.00
Methanol = 370 369.26
Palladium Carbon = 4 3.99
PRODUCT : Perampanel
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2-(1,3,2-Dioxaborolan-2-yl) benzonitrile = 5 5.01
2,3'-Bipyridin-6'(1'H)-one = 4 4.00
Copper Acetate = 6 6.01
Copper Iodide = 4 4.00
Methylene Dichloride = 10 10.01
N-Bromo Succinimide = 6 6.01
Palladium Acetate = 1 1.00
Phenylboronic acid = 5 5.01
Toluene = 10 10.01
Triphenylphosphine = 4 4.00
89
ANNEXURE - VII
PRODUCT : 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-
(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidine-
2,4(1H,3H)-dione
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
((2R,3R,4R)-3-(Benzoyloxy)-4-fluoro-4-methyl-5-
= 446 41.63
oxotetra hydrofuran-2-yl)methyl benzoate
Acetic acid = 2100 196
Ammonia (20%) = 78 7.28
Ammonium Sulfate = 10 0.93
Chlorobenzene = 4000 373.33
Citric acid (15%) = 3400 317.33
Ethyl Acetate = 730 68.13
Hexamethyldisilazane = 1635 152.6
Hydrochloric acid (35%) = 668 62.35
Isopropyl Alcohol = 4200 392
Methanol = 2090 195.07
Methylene Dichloride = 8400 784
N-(2-Oxo-1,2-dihydropyrimidin-4-yl)benzamide = 268 25.01
Potassium Hydroxide (7%) = 4000 373.33
Sodium Bicarbonate (5%) = 7808 728.75
Sodium Chloride = 134 12.51
Sulfuryl Chloride = 232 21.65
Tin Chloride = 165 15.4
Toluene = 4460 416.27
Triethylamine = 348 32.48
Vitride (70%) in Toluene = 401 37.43
90
ANNEXURE - VII
PRODUCT : (S)-Isopropyl-2-(((R)-(perfluorophenoxy)
(phenoxy)phosphoryl)amino) propanoate
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
(S)-Isopropyl-2-aminopropanoate Hydrochloride = 56 9.33
2,3,4,5,6-Pentafluorophenol = 60 10
Ethyl Acetate = 1000 166.67
Hexane = 680 113.33
Methyl tert-Butyl ether = 120 20
Methylene Dichloride = 1070 178.33
Phenyl Phosphodichloridate = 67 11.17
Sodium Chloride = 1 0.17
Triethylamine = 100 16.67
91
ANNEXURE - VII
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
1,1'-([1,1'-Biphenyl]-4,4'-diyl) diethanone = 94 15.67
1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide
= 93 15.5
Hydrochloride
Acetic acid = 640 106.67
Acetonitrile = 1130 188.33
Ammonium Acetate = 110 18.33
BOC-L-Proline = 130 21.67
Bromine = 65 10.83
Diisopropylethylamine = 76 12.67
Dimethyl Sulfoxide = 110 18.33
Ethanol = 670 111.67
Ethyl Acetate = 570 95
Hydrochloric acid (35%) = 182 30.33
Hydroxybenzotriazole = 72 12
Isopropyl Alcohol = 2210 368.33
Isopropyl Alcohol Hydrochloride (15%) = 222 37
Methanol = 2430 405
Methylene Dichloride = 1830 305
N-(Methoxycarbonyl)-L-valine = 82 13.67
N-Methyl Pyrrolidone = 280 46.67
Sodium Bicarbonate = 78 13
Tetrahydrofuran = 470 78.33
Toluene = 1240 206.67
Triethylamine = 100 16.67
92
ANNEXURE - VII
PRODUCT : Rifaximin
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2-Amino-4-methylpyridine = 68 25.56
Acetic acid = 32 12.03
Ascorbic acid = 4 1.50
Ethanol = 810 304.51
Hydrochloric acid (35%) = 23 8.65
Iodine = 3 1.13
Rifamycin-O = 158 59.40
PRODUCT : Linezolid
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2-[(2S)-Oxiran-2-yl-methyl]-1H-isoindole-1,3(2H)-
= 210 105
dione
Acetic Anhydride = 83 41.5
Ammonia (25%) = 190 95
Dimethylformamide = 120 60
Ethyl Acetate = 550 275
Hydrochloric acid (35%) = 220 110
Methanol = 120 60
Methyl-[3-fluoro-4-(morpholin-4-yl)phenyl]carbamate = 265 132.5
Methylene Dichloride = 2660 1330
Monomethylamine (40%) = 214 107
Triethylamine = 7 3.5
93
ANNEXURE - VII
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
Calcium Acetate = 27 18.81
Dimethyl Sulfoxide = 620 431.84
Hydrochloric acid (35%) = 28 19.50
Methanol = 1510 1051.74
Methyl tert-Butyl ether = 280 195.02
N-[5-(Bromomethyl)-4-(-4-Fluorophenyl)-6-propan-2-
yl) pyrimidin-2-yl]-N-methyl methanesulfonamide = 182 126.77
phosphonium salt
Potassium Carbonate = 95 66.17
Sodium Hydroxide = 14 9.75
tert-Butyl-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-
= 70 48.76
4-yl] acetate
Toluene = 1125 783.58
PRODUCT : Pregabalin
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
Acetic acid = 370 73.85
Diethyl-(1-cyano-3-methylbutyl) propanedioate = 1130 225.55
Hydrochloric acid (35%) = 160 31.94
Hydrogen = 20 3.99
Isopropyl Alcohol = 370 73.85
Methanol = 6500 1297.41
Potassium Hydroxide = 250 49.90
Raney Nickel = 714 142.51
S(+) Mandelic acid = 647 129.14
Sodium Hydroxide = 125 24.95
94
ANNEXURE - VII
PRODUCT : Flurbiprofen
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2,4-Difluoronitrobenzene = 104 67.26
Acetic acid = 135 87.31
Copper Powder = 17 11.00
Diethyl methylmalonate = 114 73.73
Dimethylformamide = 320 206.97
Hydrogen = 5 3.23
Isopropyl Nitrite = 29 18.76
Methanol = 1040 672.64
Palladium Carbon = 2 1.29
Sodium Hydroxide = 92 59.50
Toluene = 1945 1257.96
Trichloroacetic acid = 92 59.50
95
ANNEXURE - VII
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
1H-Indole-5-carbonitrile = 152 22.8
2-(2-Ethoxyethoxy)ethanol (Carbitol) = 240 36
4-Chlorobutyryl Chloride = 226 33.9
Acetone = 1810 271.5
Aluminium Chloride = 110 16.5
Ammonia (20%) = 200 30
Bis(2-chloroethyl)amine Hydrochloride = 193 28.95
Dimethylformamide = 500 75
Ethyl Acetate = 8430 1264.5
Ethyl Acetate Hydrochloride (12%) = 333 49.95
Ethyl-5-nitro-1-benzofuran-2-carboxylate = 254 38.1
Hydrochloric acid (35%) = 563 84.45
Hydrogen = 7 1.05
Isopropyl Alcohol = 590 88.5
Methanol = 3560 534
Methylene Dichloride = 1670 250.5
Nitromethane = 300 45
N-Methyl Pyrrolidone 700 105
o -Xylene = 500 75
Palladium Carbon = 13 1.95
Sodium Borohydride = 40 6
Sodium Carbonate = 291 43.65
Sodium Hydroxide = 63 9.45
Sodium Iodide = 72 10.8
Tetrahydrofuran = 990 148.5
Trifluoroacetic acid = 590 88.5
96
ANNEXURE - VII
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
(S,E)-1-(3-(2-(7-Chloroquinolin-2-yl)vinyl)phenyl)-3-(2-
= 62 61.69
(2-hydroxy propan-2-yl)phenyl)propan-1-ol
2-(1-(Mercaptomethyl)cyclopropyl) acetic acid = 27 26.87
Acetic acid = 22 21.89
Acetonitrile = 790 786.07
Diisopropylethylamine = 28 27.86
Dimethyl Sulfoxide = 330 328.36
Methanesulfonyl Chloride = 22 21.89
Methanol = 360 358.21
n-Heptane = 400 398.01
Petroleum Ether = 125 124.38
Sodium Hydroxide = 21 20.90
Sodium Methoxide (25%) in Methanol = 74 73.63
tert-Butylamine = 13 12.94
Toluene = 1220 1213.93
PRODUCT : Teriflunomide
LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
4-(Trifluoromethyl)aniline = 7 17.41
5-Methyl isoxazole-4-carboxylic acid = 5 12.44
Acetone = 130 323.38
Hydrochloric acid (35%) = 12 29.85
Methanol = 40 99.50
Methylene Dichloride = 50 124.38
Phosphorous Pentachloride = 13 32.34
Potassium Bicarbonate = 34 84.58
Sodium Hydroxide = 2 4.98
97
ANNEXURE - VII
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
17-Iodo androsta-5,16-diene-3-β-ol = 49 122.5
3-Diethylboropyridine = 20 50
Acetyl Chloride = 6 15
Bis(Triphenylphosphine) palladium(II) dichloride = 1 2.5
Ethanol = 80 200
Ethyl Acetate = 200 500
Sodium Carbonate (20%) = 200 500
Tetrahydrofuran = 240 600
Toluene = 80 200
Triethylamine = 10 25
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
[(4-Cyanophenyl)amino]acetic acid = 193 42.89
Acetone = 4050 900
Ammonia (20%) = 301 66.89
Carbonyldiimidazole = 178 39.56
Ethanol = 1800 400
Ethyl Acetate = 1750 388.89
Ethyl-3-{[3-amino-4-(methylamino) benzoyl](pyridin-2-
= 251 55.78
yl)amino} propanoate
Hydrogen Chloride = 25 5.56
Methanesulfonic acid = 60 13.33
Methylene Dichloride = 1260 280
n-Hexyl Chloroformate = 95 21.11
Potassium Carbonate = 97 21.56
tert-Butanol = 2260 502.22
Toluene = 1250 277.78
98
ANNEXURE - VIII
Raw Material
1,4-Dioxane
2,6-Dimethyl Aniline
Acetic acid
Acetic Anhydride
Acetone
Acetonitrile
Ammonium Hydroxide (28%)
Bromine
Chloroacetic Acid
Chloroform
Chlorosulfonic Acid
Cyclopentadiene
Ethanol
Ethyl Acetate
Ethylene Dichloride
Hydrobromic Acid (48%)
Hydrochloric Acid (36%)
Hydrogen
Isopropyl Alcohol
Methanol
Methylene Dichloride
n-Hexane
Pyridine
Sufluric Acid
Tetrahydrofuran
Thio Urea
Thionyl Chloride
Toluene
Butyl Alcohol
Chlorobenzene
Hydrogen Chloride
Hydrogen Fluoride
Methyl vinyl ketone
Monomethylamine (40%)
Morpholine
o -Xylene
Phosphorous Pentachloride
tert-Butylamine
Triethylamine
99
ANNEXURE - IX
100
ANNEXURE - X
Effluent Treatment Flow Scheme
Steam Stripper
Condenser
Pre aeration
tank
MEE System
ATFD
Effluent inlet
Filtrate
Sludge recycle
Sludge Decanter/
SDBS and dried
sludge to TSDF Sludge Decanter/
ACF
Salts to TSDF
SDBS and dried
sludge to TSDF
Product water to
R.O. System
Storage
Utilities
Rejects RO / Used to Tank
Cooling Tower
Evaporation
Forced
Condensate to
Utilities Salts to TSDF
101
Schematic flow Sheet for EIA Procedure ANNEXURE - XI
Category A Project
30 days on obtaining
Preparation of FORM I Application & Prefeasibility report information from industry
as per check list
Submission of application by proponent (Form 1, Pre-feasilibility report and Draft Terms of Reference)
Scrutiny 60 days
by EAC
Scoping
Scoping an communication of Terms of Reference for EIA Studies to the Proponent for EIA preparation
Public Consultancy
45 days
Conducting public hearing by SPCB / PCC or any other public Agency / authority engaged by regulatory authority
Appraisal
60 days
Appraisal by EAC
45 days
Issuing clearance to project
Decision of
MoEF proponent Decision Making
Specific Concerns
60 days
Reservation on the proposal conveyed to EAC
NO Yes
Decision
Rejection of MoEF
102
ANNEXURE - XI
Approach of EIA Study – 4 months other than monsoon period after
obtaining TOR copy from MOEF
Project Features
EIA Team Valued Environment
(Pre-feasibility Report,
Components
Form1)
Mitigation Measures
Reporting
103
ANNEXURE - XII
Topomap of 10km Radius for the Proposed Project – Orygamus Laboratories Pvt. Ltd.
104
ANNEXURE - XIII
105
ANNEXURE -XIV
106
ANNEXURE -XIV
107
ANNEXURE -XIV
108
ANNEXURE -XIV
109