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Expansion project for manufacturing of Sterile Bulk Formulation

and Injectable Formulation

Rajasthan Antibiotic Limited

RIICO Industrial Area,

Bhiwadi

Environment Consultant

Vardan Environet

(QCI and NABET/EIA/1316/IA001)

D-142, Sushant Lok-III, Sector 57

Gurgaon (Haryana)

Contact no.- 9810355569

Mail ID: vardanenviro165@gmail.com

Contact No. 0124-4291036, 09899651342

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PRE-FEASIBILITY REPORT 1.0 INTRODUCTION

Earlier, the assessment of the projects was done on Technical feasibility reports and

Cost-Benefit-Ratio which mainly considered financial & technical resources. But no

consideration was given to the environment protection in this evaluation and these

flaws became apparent with continuous deterioration of environment. Thus in

order to have more realistic evaluation, and keeping in view the deteriorating

conditions, another dimension was added which is now called as “Environmental

Impact Assessment” (E.I.A.). This forms an integral part of the project and is taken

into account while appraising the project at different stages. Thus in the new

comprehensive approach all considerations like, Technical, Financial &

Environmental are given due weightage.

Rajasthan Antibiotic Limited is proposing a project for manufacturing of Sterile

Bulk Formulation and Injectable Formulation at Plot No. 619 & 630, RIA Bhiwadi,

Tijara, Alwar Rajsthan.

As per EIA Notification dated 14th Sept., 2006 and amended from time to time, the

proposed project falls under Category “A”, Project or Activity 5(f). They have to

submit Form-I along with Pre-Feasibility Report and other relevant documents for

getting Environmental Clearance. This pre-feasibility report has, therefore, been

prepared by the consultant to assess the likely impact of the proposed on various

factors which may be affected with the implementation of the programme and to

suggest remedial/precautionary measures, if any.

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2.1 Need for installation of project

The proposed project is a bulk drug manufacturing project. These bulk drugs are used

in the manufacture of medicines, most of which are life saving drugs. The demand of

such products is tremendous in our country and there is a huge gap in the demand

and supply chain. The market of these products has a fast progressing growth and

there is ample opportunity in indigenous as well as export market.

Most of the raw materials are indigenous. Also there is easy availability of

infrastructure, man power and easy availability of raw materials. This results in the

availability of cheaper products than imported products. Due to above reasons it will

bring revenue to the state exchequer also.

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Table 1: List of products

Sr. No. Name of Proposed Product Sterile Bulk Drug Formulation

Production Capacity/Month

Storage Capacity at the Site

1. Acyclovir IP/BP/USP (Sterile) 300 MT or Combined 300 MT

350 MT 2. Amoxicillin Sodium IP/BP (Sterile) 3. Benzyl penicillin Sodium IP/BP (Sterile) 4. Cloxacillin Sodium IP/BP/USP (Sterile) 5. Ceftrioxone Sodium IP/BP/USP (Sterile) 6. Cilastain Sodium USP/BP (Sterile) 7. Dicloxacillin Sodium BP/USP (Sterile) 8. Esomeprazole Sodium (Sterile) 9. Imipenem IP/BP/USP (Sterile) 10. Meropenem IP/USP (Sterile) 11. Omeprazole Sodium BP (Sterile) 12. Piperacillin Sodium BP (Sterile) 13. Piperacillin Sodium and Tazobactum Sodium

USP (8:1) (Sterile) 14. Pantoprazole Sodium USP (Lyophilized)

(Sterile) 15. Rabeprazole Sodium IP (Sterile) 16. Sodium Carbonate IP/USP (Sterile) 17. Sodium Bicarbonate IP/USP (Sterile) 18. Sulbactam Sodium BP/USP (Sterile) 19. Tazobactum Sodium (Sterile) 20. Azithromycin IP/BP/USP (Sterile) 21. Vancomycin Hydrochloride IP/BP/USP (Sterile

Powder) 22. Clarithromycin IP/BP/USP (Sterile Powder) 23. Teicoplanin BP (Sterile Powder) 24. Ketoprofen (Sterile Powder) BP 25. Tenoxicam (Sterile Powder) BP 26. Tegicylin Sterile 27. Lansoprazole Sterile IP/BP/USP 28. Ganciclovir Sterile BP/USP 29. Antracurium Besylate UPS (Sterile) 30. Clopidogrel Hydrogen Sulphate BP/USP (Sterile) 31. Meloxicam BP (Sterile)/MELOSICAM USP

(Sterile) 32. Piroxicam BP (Sterile)/PIROXICAM USP (Sterile) 33. Rocuronium Bromide USP (Sterile) 34. Teofovir Disoproxil Fummerate IP/USP (Sterile) 35. Voriconazole USP (Sterile) 36. Oxacillin Sodium Sterile USP 37. Flucloxacillin Sodium Sterile BP/USP/EP 38. Amoxicillin Sodium and Flucloxacillin Sodium

Sterile (1:1) 39. Ampicillin Sodium and Cloxacillin Sodium Sterile

(1:1)

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Sr. No. Name of Proposed Product Finish Injectable Formulation

Production Capacity/Month

Storage Capacity at the site

1. Omeprazole for Injection 40mg 120.0 Lacs Vials or Combined 120.0 Lac Vials

150.0 Lac Vials

2. Pantoprazole for Injection 40mg

3. Esomeprazole Sodium Powder for Sodium for Injection 40mg

4. Rabeprazole Sodium for Injection 20mg/vial

5. Aciclovir Intravenous Infusion IP 250mg/vial

6. Amphotericin B Injection IP 50mg

7. Tigecycline powder for Injection 50 mg

8. Teicoplannin for Injection 400 mg

9. Voriconazole for injection 200 mg

10. Vancomycin Hcl for Intravenous infusion 500 mg

11. Vancomycin Hcl for Intravenous infusion 500 mg

12. Vacuronium Bromide for Injection 4mg/vial

13. Rocuronium Bromide for Injection 50mg/ml

14. Lancoprozole for Injection 30mg/vial

15. Ganciclovir for injection USP 500mg/vial

16. Lornoxicam for injection 8mg/vial

17. Bivalirudin Injection 250 mg/vial

18. Caspofugin Acetate for injection 50 mg/ml

19. Capremycin Injection IP 100mg/vial

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3.0 BASELINE ENVIRONMENTAL SETTING

3.1 The State

Rajasthan is India's largest state by area (342,239 square kilometres (132,139 sq

mi) or 10.4% of India's total area). It is located on the northern side of the country,

where it comprises most of the wide and inhospitable Thar Desert (also known as

the "Rajasthan Desert" and "Great Indian Desert") and shares a border with the

Pakistani provinces of Punjab to the northwest and Sindh to the west, along the

Sutlej-Indus river valley. Elsewhere it is bordered by the other Indian states: Punjab

to the north; Haryana and Uttar Pradesh to the northeast; Madhya Pradesh to the

southeast; and Gujarat to the southwest. Its features include the ruins of the Indus

Valley Civilization at Kalibanga; the Dilwara Temples, a Jain pilgrimage site at

Rajasthan's only hill station, Mount Abu, in the ancient Aravalli mountain range;

and, in eastern Rajasthan, the Keoladeo National Park near Bharatpur, a World

Heritage Site known for its bird life. Rajasthan is also home to two national tiger

reserves, the Ranthambore National Park in Sawai Madhopur and Sariska Tiger

Reserve in Alwar.

The state was formed on 30 March 1949 when Rajputana – the name adopted by

British Raj for its dependencies in the region – was merged into the Dominion of

India. Its capital and largest city is Jaipur, located on the state's eastern side.

3.2 District Bhiwadi

Bhiwadi is a city in the Alwar district of the Indian state of Rajasthan. Bhiwadi comes

under the jurisdiction of the National Capital Region. It is an industrial hub and lies

on the Rajasthan-Haryana border, adjacent to Dharuhera the town of Haryana.

Dharuhera and Bhiwadi form one urban sprawl. Bhiwadi is dominated by Veer

Gujjars

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Bhiwadi is also popular as a pilgrimage place. It is the land of 'Baba Mohan Ram', the

rider god on the blue horse. Every year thousands of worshippers from across the

country visit the temple to worship the Lord.

3.3 Project Site

The Plant site is located at Plot No. 619 & 630, RIA Bhiwadi, Tijara, Alwar Rajsthan.

It lies near Long: 76°51'28.07"E and Lat: 28°12'23.63"N and is at an Altitude of

about 266 m above mean sea level. It is about 1.5 Km away from Bhiwadi . The

nearest railway station is Rewari Railway station-which is at a distance of about 20

km from the project site. It is about 3.0 km from NH-71B.

Figure 1 : Google Image

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4.0 PROJECT DESCRIPTIONS

4.1 Raw Materials Requirement

Table 3 : Raw material requirement

Sr. No. Name of Raw Material Type Total Quantity

1. Chloramphenicol Sodium Succinate Sterile

A. Chloramphenicol Hemi-Succinate

Active Ingredients 36 MT/A

B. Ethyl Acetate Solvent 245 KL/A

C. Succinic Anhydride Excipient 2625 Kg/A

D. Tri Sodium Phosphate Excipient 357 Kg/A

E. Mono Ethyl Amine Solvent 1946 Kg/A

F. Thinner Solvent 592 KL/A

G. HCl Solvent 28 KL/A

H. EDTA Excipient 80 Kg/A

I. Sodium Hydroxide Excipient 700 Kg/A

2. Ampicillin Sodium Sterile

A. Ampicillin Trihydrate Active Ingredients 36 MT/A

B. Acetonitrile Solvent 290 KL/A

C. Di-Ethyl Amine Solvent 72 KL/A

D. Sodium Thio Cynate Excipient 4680 Kg/A

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MANUFACTURING PROCESS DESCRIPTION :

GENERAL MANUFACTURING PROCESS OF STERILE BULK FORMULATION

APIs (Non-Sterile)

Dissolve in Water for Injection/ Solvent (In Solution Preparation Tank)

(No Chemical reaction occurred during solution preparation)

Adjust the pH of the solution by using Sodium Hydroxide/HCl or other base as per requirement

(pH adjustment of solution due to human blood intake product)

Filtration the Solution by cartridge filter

(Filtration is a sterilization process to remove Bacterial Endotoxins)

(Process to low temperature for

product freezing and heating to

high temperature to remove

water and formed sterile bulk

powder)

Precipitation of solution to formed

wet cake and apply vacumm to

suck solvents

Process of heating under vacumm

to high temperature to remove solvents/water and formed Sterile

Bulk Powder

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Process Flow Chart of Chloramphenicol Sodium Succinate Sterile

Chloramphenicol Hemi Succinate

+5% NaoH Solution

WFI Addition

Solution Preparation tank

Filter 1.2 Micron cartridge

filter Cylindrical 20”

Filter 0.2 Micron membrane

filter cylindrical 20”

Filter 0.2 Micron membrane

filter Cylindrical 20”

- C for 10-12 Hrs.

C for 80-84 hrs.

Unloading

Milling

Blanding

Sampling & Analysis

Packing & Labelling

Finished Good Store

Dispatch

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Process Flow Chart of Ampicillin Sodium Sterile

Acetonitrile

Ampicillin Trihydrate

Di-Ethyl Amine

Acetonitrile

Sodium Thio Cynate

Solution Preparation Tank 01

Solution Preparation tank 02

1.2 µ Cartridge Filter

0.2 µ Cartridge Filter

1.2 µ Cartridge Filter

0.2 µ Cartridge Filter

Crystallizer

Nuctch

filter

Vacumm Tray Dryer

Milling

Blending

Packing & Labelling

Finished Good Store

Dispatch

Sampling

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Detailed About Manufacturing Process of Chloramphenicol Sodium Succinate Sterile

The Process is a one stage reaction, in which Chloramphenicol hemi succinate is charged in

a SS Reactor which contains water for injection. To this reaction mass 10 % w/v Sodium

Hydroxide Solution is added slowly and the reaction stirred continuously till

Chloramphenicol hemi succinate is completely dissolved. emperature of reaction mass is

maintained C during the process. Adjust pH 6.8 to 7.0 with caustic solution.

The solution formed in reactor is transferred to a lyophiliser in sterile area through ilter

press with ilters of si e . , . and . . he temperature in the lyophiliser is reduced

to - C and maintained for 1.0 to 2.0 hours.

The dried product is then subjected to milling and blending and, fill into the depyrogenated

aluminium container. Sample filled container to be drawn by QC for analysis. The filled

container send to finished goods store for waiting for analysis result. Approved materials

to be dispatched.

Detail about Manufacturing Process of Ampicillin Sodium Sterile

Ampiciliin Trihydrate are dissolved in Acetonitrile & Di-Ethyl amine and transferred to a

Crystallizer in Sterile Area through filter press with depth filters and Cartridge filter size

1.2 µ, 0.2 µ and 0.2 µ.

Charge of Acetonitrile in Reactor, Check moisture (between 3.5%-4.5%) and then add

Sodium Thiocyanate in Reactor, Stir to Mix well.

Check Clarity and Moisture {M/C (between 3.6% to 4.2 %)} after that transfer Sodium

Thiocyanate solution through press filter, 1.2 µ, 0.2 µ and 0.2 µ filters to Crystallizer

reactor. Transfer Acetonitrile flushing from one reactor to another reactor.

Charge Acetonitrile in another reactor, Cool Acetonitrile solution to (- 5 C. Check the

moisture NMT 1.0%. After that add Ampicillin Trihydrate in 10-20 min.

Add Diethyl Amine (DEA) in 10-20 min. Stir to mix well, check clarity, moisture (M/C) & pH

{M/C NMT 5.0% & PH (9.50 -10.50)}.

Start transferring drug solution through press filter 1.2 µ, 0.2 µ and 0.2 µ filters to reactor.

Transfer Acetonitrile flushing from one reactor to another reactor. Precipitation for 180

min.

Transfer slurry solution from reactor to nutsch filters by applying pressure. Suck dry under

vacumm and Slurry wash wet cake with acetonitrile.

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Suck dry under vacumm slurry wash wet cake with Acetonitrile. Final suction load the

material under LAF in to VTD trays. Apply Vacumm & dry under vacumm for 60-120 min.

Apply hot water circulation and dry material till M/C less than 1.0.

The dried product is then subjected to milling and blending to get uniform material. Then

material packing in pre sterilized & depyrogenated Aluminum containers and sample for

final QC check. Approved materials to be dispatched.

List of Additional Equipment for approval for Dry Powder filled Vial:

Vial Washing Machine

Sealing machine

Sterilize Tunnel

Powder filling machine

Stoppering Machine

Vial Inspection Table

Bung Washer

Labeling Machine

Facilities at the Plant

Total project area is 2100 m2. It provides adequate space for the following areas of

working:-

1. Storage for raw material and finished goods.

2. Plant and Machinery

3. Storage

4. Offices

5. Toilets

6. Water storage tanks

Open space will be landscaped and trees will be planted in due course of time.

4.2 Power Requirement

Total power requirement for the proposed expansion project is 2500 KW.

4.6 Water Supply

The total raw water requirement for proposed unit will be 50 m3/Day.

Source: - RIICO , Rajasthan

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5.0 SITE ANALYSIS (i) Connectivity

The Plant site is located at Plot No. 619 & 630, RIA Bhiwadi, Tijara, Alwar

Rajsthan. It lies near Long: 76°51'28.07"E and Lat: 28°12'23.63"N and is at an

Altitude of about 266 m above mean sea level. It is about 1.5 Km away from

Bhiwadi. The nearest railway station is Rewari Railway station-which is at a

distance of about 20 km from the project site. It is about 3.0 km from NH-71B.

Rainfall and Temperature:

The minimum temperature in operational area comes down to 5.00C during

winter in January and it increases upto 37.00C in the month of June. However, it

has been informed that the rainfall in operational area is good.

Irrigation

Irrigation is a critical input in agriculture. The need for increased food-grain

production in the district relates to development of water resources and its

management. Ground water resources are more sustainable even under period of

moisture stress and, therefore, greater emphasis is being laid on the optimum

development and efficient management of these resources on scientific lines.

Most importantly, irrigation acts as a buffer under drought conditions, whereby

the protective irrigation can prevent crop loss.

Topography The topography of the area is flat.

Social Infrastructure available

There are no primary schools, dispensaries, small hospitals, places of worship in

nearby area of the project site.

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(vi) Proposed infrastructure

(a) Industrial Area (processing area)

It is an industrial land

(b) Residential Area (Non processing area)

Residential colony is not proposed for proposed project. The local labor will

be preferred to provide employment opportunities.

(c) Green Belt

Greenbelt will be developed in 33% of the total area of the proposed project.

(d) Social Infrastructure Proposed project will result in growth of the surrounding areas by increased

direct and indirect employment opportunities in the region including

ancillary development and supporting infrastructure.

(e) Connectivity The project is well connected with Rail and Road.

(f) Industrial Waste management

The proposed plant would be based on “ZERO EFFLUENT DISCHARGE”.

6.0 REHABILITATION AND RESETTLEMENT (R & R) PLAN

No Rehabilitation and Resettlement plan is applicable because there are no

Rehabilitation & Resettlement of the people.

7.0 Project Schedule and Cost Estimates

The project will start only after obtaining Environmental Clearance and all other

required clearance and will complete after two years of commencement.

The Capital Cost of the project is Rs 500 lakhs.

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8.0 WASTE MANAGEMENT

8.1 Liquid Effluent:

We have already constructed water pit in which all discharge and stream water

collected and it is reused and recycled in our system on regular practice.

8.2 Air Pollution:

We are processing all our operation in closed circuit, hence there is not any fugitive

emission form the project.

8.3 Solid Waste:

Process Residue and Wastes and Discarded containers/barells/liners used for

hazardous wastes/chemicals will be sent to CTDF Udaipur. Used /Spent Oil will be

sold to authorized recycler.

8.4 Noise Pollution Control:

There is no danger of noise pollution from plant. The green belt will (plantation of

dense trees across the boundary) help in reducing noise levels in proposed plant as

a result of attenuation of noise generated due to plant operations, and

transportation.

Earmuffs would be used while running the equipments of the plant.

D.G sets are provided with acoustic to control the noise level within

the prescribed limit.

A high standard of maintenance will be practiced for plant machinery

and equipments, which helps to avert potential noise problems.

9.0 GREEN BELT DEVELOPMENT/ PLANTATION

Green belt development in and around the project site helps in to attenuate the

pollution level. About 33% land area of project will be developed as green belt and it

will be maintained in future also. Green belt will be developed as per Central

Pollution Control Board (CPCB) Norms. The Avenue plantation will give priority to

native species, and the periphery will be devoted to generation of green belt area.

10.0 CSR Activities

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Proposed project will result in growth of the surrounding areas by increased direct

and indirect employment opportunities in the region including ancillary

development and supporting infrastructure. Special emphasis on Financial and

Social benefits will be given to the local people including tribal population, if any, in

the area. Development of social amenities will be in the form of medical facilities,

education to underprivileged and creation of self help groups.

No adverse effect on environment is envisaged as proper mitigation measures

will be taken up for the same.

-.-.-.-.-.-.