Report Pharma

Pharmaceuti cal Sector
Environmental Report
May, 2002
Prepared by:
C P P
Cleaner Production Program
Environmental Report
May, 2002
Prepared by:
Cleaner Production Program - CPP 703, 7 Floor, Progressive Plaza, Beaumont Road, Civil Lines, Karachi. Tel #: +92-21-565 5835, 565 5836 Fax #: +92-21-565 5737 Email: cpp@cyber.net.pk , URL: http://www.cpp.org.pk
th
Table of Content
Preface Executive Summary
vi vii
1 Introduction 1.1 1.2 1.3 Background Overview of the Pharmaceutical Sector Environmental Report Pharmaceutical Sector of Pakistan 2 1 2
2 Production Process 2.1 Raw Materials and Products 2.1.1 Products 2.1.2 Raw Materials 2.2 Main Production Facilities 5 2.2.1 Storage Facilities 2.2.2 Manufacturing Facilities 6 2.2.3 Over Printing Area 6 2.2.4 Packaging Area 7 2.3 2.3.1 2.3.2 2.3.3 2.3.4 2.3.5 2.3.6 2.3.7 2.3.8 2.3.9 2.3.10 2.3.11 2.3.12 Allied Facilities 7 Quality Control (QC/QA) Laboratory Ventilation Systems Chillers and Cooling Towers Fire Detection and Fighting Systems Boilers Water Softening Units Water De-ionizing Units Water Distillation Unit Generators Hydraulic Press Shredder Incinerator 5 5 5
7 7 7 7 7 8 8 8 8 8 8 8 9 9
2.4 Typical Production Processes 2.4.1 Dispensing
Table of Content
Pharmaceutical Sector Report
2.4.2 2.4.3 2.4.4 2.4.5
Tablets Manufacturing Encapsulation Syrups manufacturing Manufacturing of Oral Powders for Suspensions and Lotions Manufacturing 10 2.4.7 Ijectibles Manufacturing 11 2.4.8 Capsul Manufacturing Process 11
9 10 10 10 2.4.6 Creams, Ointments
Cleaner Producti on Program (CPP)
Page # i
2.5
Utilities 12 2.5.1 Water 2.5.2 Electricity 2.5.3 Fuels 3 Environmental Issues and Impacts 3.1 3.1.1 3.1.2 3.1.3 3.1.4 3.1.5 3.1.6 3.2 3.2.1 3.2.2 3.2.3 3.2.4 3.3 Wastewater Pollution General Wastewater Sources and Quality Wastewater Quantities Wastewater Characteristics Impacts Associated with Wastewater Disposal of Wastewater
12 12 13
14 14 14 16 16 17 18
Air Emissions 19 Major Sources, Process and Qualitative Characteristics of Air Emission 19 Existing Situation on Point Emissions 20 Existing Situation on Diffused Emissions 21 Impacts of Air Pollutants on Environment and Human Health & Life 21
Process Solid Waste and Waste Chemicals 23 3.3.1 Contaminated Process Solid waste and Waste Chemicals 3.3.2 Existing Disposal Practices of Contaminated Solid Waste 3.3.3 Non-Contaminated Process Solid Waste 3.4 Noise Pollution 25 3.4.1 Noise Sources and Levels 3.4.2 Potential Impacts of Noise Pollution 4 Recommendations
Cleaner Production Program (CPP)
23 24 25
25 26
Page # ii
Table of Content
4.1 4.1.1 4.1.2 4.1.3 4.1.4
Wastewater Treatment General Wastewater Quantities Wastewater Characteristics and Effluent Quality Standards Proposed Wastewater Treatment system for Removal of Organic Pollutants 4.1.5 Activated Carbon Adsorption Treatment for Removal of Phenols 4.2 4.2.1 4.2.2 4.2.3 4.2.4 4.2.5
27 27 27 27 28 31
Occupational Air Quality Control 31 Enclosure of the Emission Sources Criteria for Local or Spot Ventilation System 32 Criteria for General Area or Room Ventilation System Monitoring Exhaust or Re-circulating Air Carrying Particulate Matter from Granule & powdered Ingredients Processes Contaminated Solid Waste and Waste Chemicals and Management Waste Segregation and Quantification Prevention of Waste Generation Storage of Contaminated Waste and Waste Chemicals Contaminated Waste Treatment and Disposal by Incineration Contaminated Glassware Contaminated Emptied Drums
32 34 35 35 35
4.3 4.3.1 4.3.2 4.3.3 4.3.4 4.3.5 4.3.6 4.5
35 36 36 36 38 38
Occupational Health and Safety (OHS) Measures 38 4.5.1 Material Safety Data Sheets (MSDS) for Hazardous Substances 39 4.5.2 Fire Fighting System 39 4.5.3 Personal Protection Equipment (PPE) 40 4.5.4 First Aid Medical Treatment 40 4.5.5 Uniforms 40 4.5.6 Training and Procedures 40 4.5.7 Records and Evaluation 41 Recommended Institutional Measures 4.6.1 Defining and Setting Objective and Policies 4.6.2 Areas of Responsibilities of EHS Department 4.6.3 Functions of EHS Department 41 41 41 42
4.6
Annexure
Annexure-I: Main Features of an Air Handling System
Page # iii
Table of Content
List of Tables
Table 1.1: Province wise distribution of Pharmaceutical Industries Table 1.2: Annual Sales of Top Ten Products Rs. m From January 2001 to December 2001 Table 1.3: Sales of Leading Companies Table 3.1: Typical Wastewater Generation Sources and Qualitative Characteristics Pharmaceutical Plant Table 3.2: Composite Process Wastewater Characteristics Table 3.3: Environmental Impacts of Wastewater Table 3.4: Air Emission Sources/Operations and Major Pollutants Table 3.5: Impacts of Air Pollutants on Environment and Human Health & Life Table 3.6: Contaminated process Solid Waste and Waste Chemicals Pharmaceutical Formulation Industry Table 3.7: Non-Contaminated Process Solid Waste Pharmaceutical Formulation Industry Table 3.8: Typical Noise Levels in Pharmaceutical Industry Table 4.1: Maximum Day Composite Wastewater Characteristics and Required Degree of Treatment Pharmaceutical Formulation Plant Table 4.2: Treatment Efficiencies Based on Composite Wastewater Characteristics Existing Extended Aeration Activated Sludge Plant (Pharmaceutical Formulation Plant) Table 4.3: Range of Capture velocities for Dusts, Vapors, and Fumes
Page # iv
Table of Content
List of Figures
Figure 4.1: Figure 4.2: Wastewater Treatment Plant Rotary Kiln
Page # v
Preface
This report is compiled by the Cleaner Production Program (CPP). The main objective of CPP is to continue the dissemination of environmental and cleaner production solutions and enabling the industrial units at the sector level to implement the same in a cost effective manner. This report is a step towards the dissemination of information about the environmental problems of Pharmaceutical Sector. It also recommends possible cleaner production solutions and estimated required investments to mitigate these problems in order to comply with the present and future environmental legislation in Pakistan. It is anticipated that this report will help Pharmaceutical Industries to initiate efforts to combat the environmental problems and produce cleaner pr oducts. This report on the Pharmaceutical Sector has been prepared on the basis of information collected from various pharmaceutical units, different environmental initiatives/projects under taken over the years in this sector and other substantial international secondary sources. In this regard, we thank Pakistan Pharmaceutical Manufacturers Association (PPMA) and Pharmaceutical industries for extending their support in all aspects of the study.
November, 2001
vi
Page #
Executive Summary
Environmental degradation is an escalating problem owing to the continual expansion of industrial production and high-levels of consumption. A renewed dedication to a proven strategy to resolve this problem is needed. The progressive industries of Pakistan have been taking individual steps to solve their environmental problems under the proven Cleaner Production (CP) regime. Many environmental projects have also addressed the issue and contributed towards the improvement of environmental condition of local industries. Cleaner Production Program (CPP) is an initiative that is focused on the consolidation of environmental and CP related work done in the different major industrial sectors of Pakistan. The main objective of CPP is to continue the dissemination of cleaner production solutions, and enabling the industrial units at the sector level to implement the same in a cost effective manner. Free technical assistance is available under CPP to the selected industrial units against a commitment of sharing their knowledge and experience of the implementation of CP technologies with the other units of the same sector. This report encompasses the nature and extent of environmental and public health problems associated with the Pharmaceutical sector and develop solutions in terms of cleaner production options and end-of-pipe treatment. Pharmaceutical sector can be classified as one of the most organized sector with respect to its institutional arrangements. About 200, both local and multinational industries are operating in this sector in which the market sales of the leading multinational companies are 50% . Most of the pharmaceutical industries are located in Sindh and Punjab. The production of pharmaceutical products can be broken down into three main stages: 1) Research & development; 2) Conversion of organic & natural substances into bulk pharmaceutical substances or ingredients through fermentation, extraction and/or chemical synthesis; and 3) Formulation of the final pharmaceutical product. In Pakistan, only the formulation of pharmaceutical products is carried out and wide variety of chemical and pharmaceutical products are produced which includes anesthetics, disinfectants, water soluble salt, muscle relaxants, anti clotting agents, analgesic, anti hypertensives, antibiotics, diuretics, anti-infective, cardiovascular, central nervous system and vitamin in the form of capsules, tablets, ampoules, syrups, creams, etc. Active raw materials as well as excipients like sugar, lactose etc. are used to manufacture different pharmaceutical products. Besides the major raw materials, solvents such as Methylene Chloride, Di-chloro Ethane, Ethyl Acetate and Methanol are mostly used. Most of the requirements of raw materials are met through import. Most consumed utilities in pharmaceutical industry are electricity, water, diesel and natural gas. Generally water is required in most of the processes. Beside this it is also consumed in
vii
Executive Summary
Page # Pharmaceutical Sector Report
general office use, cleaning, rinsing, washing, showering, etc. Electricity consumption depends on the size of the unit and the degree of dependence on electric appliances. Natural gas and diesel are mostly employed as fuel for heating purpose such as for water heating systems, incinerator, generator, etc. Air-handling, Generator, Boilers, Water Treatment System are some of the commonly used ancillaries in Pharmaceutical sector. In Pakistan no synthesis process is done, only for mulation, filling and packaging process is carried out in local and multinational industries. Therefore, environmental problem is not a significant issue in the sector. Being an organized sector many of the pharmaceutical industries have already taken some CP initiatives. This includes proper air handling system, use of PPE, and installations of wastewater treatment systems. Wastewater Pollution is the main issue of this sector. In pharmaceutical industries wastewater is mainly generated through the washing activities of the equipment. Solid waste usually comprises of expired or rejected medicines, spent solvents, packaging material and damaged bottles. The air emission problem, mainly from generator and boilers is not significant as compared to the wastewater and solid waste. Level of wastewater pollution varies from industry to industry depending on the type of process and the size of the industry. The main pollutants in effluent are organic chemicals (responsible for BOD & COD), Grease & Oil, sulfate, Ammonia Sulfide, Phenols, TSS, TDS, etc. Ranges of BOD & COD values of wastewater are higher than the limits defined by NEQS in all industries. While in some industries the concentration of oil&grease, sulphide and TSS are also on the higher side Air emissions are mainly from exhaust of stacks of power generator, boilers and incinerators. Emissions from these stacks mainly consist of particulate matter, NOx, SOx, CO and CO2. These emissions are due to fuel combustion. Emissions other than stacks are VOC from printing machine, tablet manufacturing area etc. Solid wastes are generated through different production activities. These includes expired or rejected medicines or capsules, empty drums, glass bottles, spillages and filter & dust from bag filters. The report also includes recommendations, which are focused on the above mentioned problems of the sector. Some of the major recommendations include reduction of wastewater from washing activities, which in turn will reduce the cost and size of wastewater treatment plant. Regarding the EOP, on the basis of the data available, it is inferred that for combined effluent (process + domestic), biological treatment with activated sludge system and sequencing batch reactor will be suitable before final disposal so as to comply with NEQS levels. Extended Aeration Activated Sludge (EAAS) process and Sequencing Batch Reactor (SBR) process, both of which are modified forms of conventional activated sludge process, can be used as treatment systems, for pharmaceutical wastewater.
viii
In activated sludge process, the wastewater treatment is carried out by forced supply of oxygen or air to the wastewater and maintaining a contact, in suspension form, between microorganisms (activated sludge) and the incoming wastewater. For the air handling system it is suggested that a procedure for its operation and maintenance should be prepared. An air handling system refers to a system designed for directing air in a
Page #
ix
Executive Summary
positive and controlled manner through specific enclosures by means of air-handling plant, ducts, air distributing devices and automatic controls. Similarly fume hood is recommended in main dust generating areas which include packaging, dispensing and mixing area. Some of the major recommendations with respect to solid waste include reduction of waste and disposal of waste under proper and safe conditions. It is suggested to set up and carry out a solid waste segregation program. The program shall also include collection and documentation of data on generation rates, collection/handling practices, storage and disposal activities, for different types of wastes. This data would be helpful in proper planning of the waste disposal operations. Hazardous and non hazardous waste should be stored separately to avoid contact between each other. Waste segregation should take place at the source of waste. All the contaminated solid waste and chemicals should be segregated from other wastes and stored under controlled conditions. Incineration is at present considered to be a suitable technology for the disposal of waste chemicals and contaminated solid waste of pharmaceutical industry. It is the controlled thermal oxidation and decomposition of organic matter, at very high temperatures. As provision of a proper in-house incineration facility would not be economically feasible for most of the units, due to the kind of contaminated waste loads encountered and the high capital cost of duly equipped incinerators. Therefore, there is need of installing a properly equipped incineration facility, jointly and collectively by a group of pharmaceutical manufacturing units through PPMA. It is recommended that the workers working in high noise areas must wear ear protection gadgets and signs for wearing ear protection gadgets must be put in the area . Technical details and cost estimates of recommended measures are included in the report to facilitate the management in taking decisions for the implementations.
Page # viii
1
Introduction
1.1 Background
Environmental degradation is an escalating problem owing to the continual expansion of industrial production and high-levels of consumption. A renewed dedication to a proven strategy to resolve this problem is needed. Cleaner Production is one such strategy which can address this problem. It is a preventive environmental management strategy, which promotes eliminating waste before it is created to systematically reduce overall pollution generation, and improve efficiencies of resource use. The definition of Cleaner Production adopted by UNEP is as follows; Cleaner Production is the continuous application of an integrated preventive environmental strategy to processes, products, and services to increase overall efficiency, and reduce risks to humans and the environment. Cleaner Production can be applied to the processes used in any industry, to products themselves and to various services provided in society. The progressive industries of Pakistan have been taking individual steps to solve their environmental problems under the proven Cleaner Production (CP) regime. Many environmental projects have also addressed the issue and contributed towards the improvement of environmental condition of local industries. Cleaner Production Program (CPP) is an initiative that is focused on the consolidation of environmental and CP related work done in the different major industrial sectors of Pakistan. The main objective of CPP is to continue the dissemination of cleaner production solutions, and enabling the industrial units at the sector level to implement the same in a cost effective manner. The CPP team will be working very closely with the progressive industrial sectors of Pakistan to conclude the cleaner production research for reducing the pollution loads. The knowledge and experience premises of the CPP are precisely based on the projects already implemented or projects under implementation for different industrial sectors of Pakistan. Predominantly the project will use the experience and knowledge of leather, textile, sugar, paper, and fertilizer sectors environmental projects. Presently, CPP is working with various industrial units of Pakistan to implement
Cleaner Production Program (CPP) 1
Introduction
cleaner production technologies as well as end-of-pipe treatment. The time frame for delivery of the project is two years.
Page #
Free technical assistance is available under CPP to the selected industrial units against a commitment of sharing their knowledge and experience of the implementation of CP technologies with the other units of the same sector. Assistance to the selected industrial units is provided for CP projects which are: Critical for the sector, for environmental compliance. Relevant and applicable to the majority of the industries in the local sector. Technically and financially feasible. Doable by December 2003.
Industrial units will be required to provide the resources for the implementation of projects along with the organization of awareness raising events, in kind, against the provision of technical assistance by the CPP technologists. The expected results, as output of CPP, would support industries to comply with National Environmental Quality Standards (NEQS) and ISO 14000. In order to ensure the sustainability of CP solutions at the sector level CPP will also prepare guidelines for the development of sector level cleaner production projects.
1.2 Overview of the Pharmaceutical Sector Environmental Report

This report for the Pharmaceutical sector is prepared on the basis of information collected from: Various pharmaceutical units, Different environmental and CP initiatives/projects undertaken over the years in the sector, and Substantial international secondary sources including internet. This report encompasses the nature and extent of environmental and public health problems associated with the pharmaceutical sector and develop solutions in terms of cleaner production options and end-of-pipe treatment. The manufacturing process is described briefly in order to better understand the problem. This is followed by a detailed analysis of the environmental issues in terms of wastewater pollution, process solid waste, air emissions and noise and their impacts on human beings and ecology. Finally, CP solutions are described to mitigate the adverse impacts associated with the above problems. The findings are generalized to ensure confidentiality of unit specific information. Maximum care has been taken while generalizing the information, however, variation from one unit to another may be expected due to specific process conditions.
1.3 Pharmaceutical Sector of Pakistan

The production of pharmaceutical products can be broken down into three main stages: 1) Research & development; 2) Conversion of organic & natural substances into bulk pharmaceutical substances or ingredients through fermentation, extraction and/or chemical synthesis; and 3) Formulation of the final pharmaceutical product. In
Page #
Introduction
Pakistan, only the formulation of pharmaceutical products is carried out and wide variety of chemical and pharmaceutical products are produced which includes anesthetics, disinfectants, water soluble salt, muscle relaxants, anti clotting agents, analgesic, anti hypertensives, antibiotics, diuretics, anti-infective, cardiovascular, central nervous system and vitamin in the form of capsules, tablets, ampoules, syrups, creams, etc. About 200, both local and multinational industries are operating in this sector. Pharmaceutical sector can be classified as one of the most organized sector with respect to its institutional arrangements. Annual sales of the top ten products in Pakistan are given as Table 1.2 . Most of the pharmaceutical industries are located in Sindh and Punjab. The province wise distribution of pharmaceutical industry is shown in the following Table 1.1, whereas major market sales of the leading multinational companies are shown in Table 1.3. Table 1.1 Province wise distribution of Pharmaceutical Industries Province Punjab Sindh NWFP Share (No.) 85 85 6
Pakistan Pharmaceutical Manufacturing Association (PPMA) represents most of these pharmaceutical companies with 176 members in their association. PPMA also has an Environmental Committee to look after the sectoral issues related to environment. Table 1.2 Annual Sales of Top Ten Products Rs. m From January 2001 to December 2001 Products Augmentin Ponstan Amoxi Velosef Flagyl Septan Ampiclox Neurobion Brufen Erythrocyin
Cleaner Production Program (CPP) 4
Company SKB P.Davis SKB BMS RPR Wellcome SKB M.Marker Knoll Abbot
Sales 767 596 586 503 396 376 370 326 314 303
Source: IMS 12 Mths data To Dec. 01
Page #
Table 1.3 Sales of Leading Companies RANKING SALES GTH OVER PERIOD OF JAN 01 TO DEC 01
EVO
SHARE %
Total Market GLAXO SMITHKLINE BEECHAM GLAXO WELLCOME SMITH KLINE & FRENCH 1 1 4 6 21 43,601 5,839 2,252 1,636 1,279 672 7.10 9.1 5.80 16.30 6.20 9.40
100 102 99 109 99 102
100.0 13.4 5.2 3.8 2.9 1.5
ABBOT + KNOLL AVENTIS HOECHST RHONE POULENC RORER NOVARTIS NOVARTIS PH.SPECIA NOVARTIS CONS.HEAL BIOCHEMIE/SERVIPH (Ciba Geigy) PFIZER INC PARKE DAVIS PFIZER MERCK MARKET +BOERI-I WYETH PAKISTAN LTD BRISTOL-MAYER SQUIBB BRISTOL-MAYER SQUIBB UPSA MSD PHARMACIA & UPJOHN ROCHE
Source: IMS
2 3 3 12 4 9 19 34
2,860 2,694 1,723 971 2,124 1,091 695 338
2.90 19.70 13.50 32.50 8.80 11.70 4.90 8.00
96 112 106 124 102 104 98 101
6.6 6.2 4.0 2.2 4.9 2.5 1.6 0.8
5 10 18 6 7 8 8 9 10 11
1,731 1,033 699 1,521 1,246 1,101 1,098 3 1,031 937 768
5.00 9.30 (0.80) 5.90 (8.30) 1.90 3.30 (81.50) 9.40 (1.60) (3.30)
98 102 93 99 86 95 96 17 102 92 90
4.0 2.4 1.6 3.5 2.9 2.5 2.5 0.0 2.4 2.2 1.8
Page # 5
Introduction
12 Mths data To Dec01
Page #
2
Production Process
This chapter contains a description of the typical production process for pharmaceutical products. As already mentioned, pharmaceutical industry is not involved in synthesis and manufacturing of basic pharmaceutical ingredients, but only carries out formulation, filling and packaging of the pharmaceutical products.
2.1 Raw Materials and Products

2.1.1 Products
Pharmaceutical industries in Pakistan formulate, fill and pack a variety of pharmaceutical products, with different trade names, in the following different forms: a. b. c. d. e. f. Tablets Capsules Syrups Oral Powders for Suspensions Creams, Ointments and Lotions Injectibles and Ampoules
2.1.2 Raw Materials

Raw materials for medicines include active pharmaceutical ingredients, excipients (like sugar and lactose) and solvents (such as methylene chloride, dichloro ethane, ethyl acetate and methanol). Most of the requirements of raw materials are met through import. Basic raw material used in the manufacturing of empty capsules is pharmaceutical grade gelatin. Gelatin is a mixture of water-soluble proteins derived primarily from collagen, which is a naturally occurring protein. Other major materials used in the
capsule manufacturing are dyes, dye -aids, preservatives and glycerin. Variety of packaging materials like glass bottles, blisters, plastic caps, aluminum seals, polythene/paper bags, cartons, carton partitions, labels and shrink wrappers are also used by pharmaceutical industries.
2.2
Main Production Facilities
2.2.1 Storage Facilities

Generally raw materials, finished products, packaging materials and expired or rejected goods are stored in separate storage areas or separate compartments within a
Page # 7
Production Process
combined warehouse. Temperature sensitive raw materials are stored in a separate cold storage room, maintained at the desirable temperature, commonly, in the range of 0-8 0C. Generally solvents are store separately. Raw materials are, mostly, kept in quarantine area after their arrival at the plant, till their quality is tested and checked by the quality control laboratory. After the testing in QC laboratory, approved and rejected materials are transferred and stored in separate sections. Some plants have installed air curtain systems at the entrances of the storage areas to restrict the entry of insects and dust. The system automatically works when the door opens or when the material enters the warehouse. In addition there are insecticutors meant for killing the insects in the warehouse and production facility.
2.2.2 Manufacturing Facilities

Generally separate manufacturing areas are provided in most of the pharmaceutical plants for different dosage forms. In some units, production of more sensitive medicines, like antibiotics, is carried out in an exclusive manufacturing area, separated from the other manufacturing areas and provided with higher level of hygiene control and biological safety. Major equipment used for production of different pharmaceutical products include: i. Mixing & Blending Vessels ii. Granulating machines iii. Drying Chambers iv. Autoclaves and Ovens v. Tablets Compression Machines vi. Tablets Coating Machines vii. Capsule Manufacturing Machines viii. Encapsulation Machines ix. A variety of purpose-built automatic or semiautomatic filling machines for liquids in bottles, liquids in ampoules vials, powders in bottles and creams & ointments in collapsible tubes x. A variety of purpose-built automatic Printing Machines
2.2.3 Over Printing Area

Printing machines, located in the printing area, are used for printing prices, batch number, and manufacturing and expiry dates, on the packaging materials and ampoules and vials. In capsule manufacturing units, purpose-built printing machines are used for printing labels, on the capsule bodies.
Page # 8
Production Process
2.2.4 Packaging Area

Medicines in bulk forms, after final approval from Quality Control (QC) Department, are sent to the packaging area for the desired packing, on the purpose-built packaging machines. Medicines are filled into the primary containers. The machines which are include: Blister machine Strip sealing machine Liquid filling machine Ointment/cream filling machine
2.3
Allied Facilities
2.3.1 Quality Control (QC/QA) Laboratory

Most of the plants maintain their own laboratories to provide for the quality control and assurance of the raw materials, packaging materials and finished products.
2.3.2 Ventilation Systems

Most of the plants have built-in forced ventilation systems, with or without airconditioning, in main process areas. The purpose of these systems is to maintain the quality of the working atmosphere by taking away the chemical fumes and vapors, released from processes to the occupational atmosphere and by supplying the fresh air to the process areas. Generally, the ventilation systems are provided with dust filters .
2.3.3 Chillers and Cooling Towers

Chillers and cooling towers are provided, where centralized air conditioning systems are installed. Cooling towers are used for the cooling of hot water generated from chillers.
2.3.4 Fire Detection and Fighting Systems

Some of the units have installed fire detection and alarm systems. Fire fighting facilities range, from plant to plant, from provision of manual fire extinguishers (carbon dioxide and/or foam) to water-based fire hydrant and/or automatic sprinkler systems.
2.3.5 Boilers
Boilers are used to produce steam, which is employed for heating in the following equipment: a. Autoclave
Page # 9
Production Process
b. c. d. e.
Tablet coating machines Distillation column for production of distilled water Centralized air-conditioning and dehumidification systems Jacketed process vessels for heating of contents Natural gas or furnace oil is used as fuel for boilers.
2.3.6 Water Softening Units

Some of the plants soften the available water for boiler feeding purposes. Generally, cation exchange units are used, for this purpose. Water softening media needs to be regenerated, periodically at an average interval of 24-48 hours, by back washing with high-strength sodium chloride solution.
2.3.7 Water De-ionizing Units

Process water in most cases needs to be of very low dissolved solids. The de-ionized water is therefore produced by reverse osmosis process.
2.3.8 Water Distillation Unit

Distilled water is used in injectibles and in a variety of other medicines. Washing of ampoules is also sometimes carried out with distilled water. Distillation process is applied to produce such water.
2.3.9 Generators
In most of the plants, electric generators are provided as standby facility, in event of main power failure. Generally these generators are diesel based.
2.3.10 Hydraulic Press

Some plants have hydraulic presses, for damaging the empty raw materials drums, prior to their dispatch to the contractor, for recycling purposes. The purpose of this activity is to prevent the possible direct reuse of these contaminated drums, by some downstream user.
2.3.11 Shredder
On-line process rejected glass bottles are mostly contaminated and therefore shall not be reused directly. Some plants have installed shredders to break the rejected bottles, prior to their dispatch to the contractor for recycling or disposal purposes. This process prevents the possible direct use of these contaminated bottles.
2.3.12 Incinerator
Page # 10
Production Process
Few plants have installed their own incineration facilities for the safe disposal of their hazardous solid and liquid wastes. Post-incineration residual ash is immobilized by fixation in cement concrete blocks.
2.4 Typical Production Processes

2.4.1 Dispensing
Raw materials are sent from storage areas to the dispensing area, where they are weighed, prior to their dispatch to the manufacturing areas. Dispensing of steroids is accomplished after mixing with a solvent in a special totally enclosed system equipped with HEPA filters.
2.4.2 Tablets Manufacturing

The manufacturing of tablets involves homogeneous mixing of input ingredients, such that when compressed into tablets, each tablet should contain equal amount of each raw material. The tablet manufacturing process involves the following steps: Sieving Initial blending and Granulation Drying and Milling Final Blending Compression Coating and drying Packaging A brief description of the above processes follows: a) Sieving: The raw materials are first sieved to remove the oversize particles and then shifted to the blending vessel. b) Initial Blending and Granulation: After sieving, materials including active ingredients and excipients are first mixed in dry form. Then the liquid mediums, like water and alcohol are added to the dry mixture in specified proportions, for the formation of granules. c) Drying and Milling: The granules are dried in the drying chamber to specified moisture content limits, at the required temperatures for a specific time period. The dried granules are then transferred to a milling machine, for grinding. Uniform size particles are obtained with the help of a screen. d) Final Blending: The final mixing is carried out in a blender, with the addition of lubricants, in specified proportions. Commonly used lubricants are magnesium stearate and stearic acid. e) Compression : The bulk materials (granules) are fed to the tablet compression machines, which compresses them to the tablets of required shape and size.
Page # 11
Production Process
The compression machines are equipped with dust collectors to collect dust generated during compression, de-dusters to remove excessive dust from the tablets.
Page # 12
Production Process
After the completion of a batch, the compression machines are cleaned with kerosene oil. Then the machines are left overnight for the evaporation of kerosene oil. f) Coating and Drying: Some of the tablets require coating. The coating solution is prepared by mixing the coating materials and water, in a vessel having an agitator for uniform mixing. The tablets are transferred to the coating pans, which are equipped with spray systems to spray the coating solution on the tablets at specified temperature. When desired weight gain is obtained the process is stopped. The coated tablets are then dried for few minutes. Finally the lubrication of the granules has been done by mixing suitable lubricants. g) Packaging : After coating, the tablets are ready for packing and are transferred to the packing section.
2.4.3 Encapsulation
Encapsulation is the process in which medicine is filled in the preformed capsules, on encapsulation machines. Ingredients pass through steps of dispensing, sieving, and blending in the same way as in the tablets manufacturing, prior to being fed to the encapsulation machine.
2.4.4 Syrups Manufacturing

Preservatives are dissolved in de-ionized water in a jacketed process vessel at temperatures of the order of 90 0C. The solution is stirred continuously and then cooled to a temperature of about 30 0C. After cooling, the active ingredients are added and stirring is restarted. Flavors are added during the process of mixing. The viscosity of the syrup is maintained by the addition of de-ionized water. After specified period of mixing, syrup is taken out of vessel, filtered and stored in large storage tank, before filling into the bottles and packing.
2.4.5 Manufacturing of Oral Powders for Suspensions

Duly formulated, mixed and homogenized powders are brought to the powder filling machines, where they are automatically filled in the bottles, in required quantities. Finally, sealing of the bottles is done. The bottles are labeled and packed before their dispatch to the finished goods store.
2.4.6 Creams, Ointments and Lotions Manufacturing

Pharmaceutical industry is producing oil-bases and water-based creams, ointments and lotions. The excipients are mixed in the jacketed process vessels, equipped with stirrers and heating arrangements. During mixing the active ingredients are added to the mixture. The prepared mixture is then stored in containers. The mixture is fed to the purpose-built automatic filling machines, which are different for different type of containers. The mixture is automatically filled, in required
Page # 13
Production Process
quantities, into collapsible aluminum tubes or bottles, as the case may be. Generally, ointments are filled in collapsible aluminum tubes, while lotions are filled in bottles.
2.4.7 Injectibles Manufacturing

Ampoules and vials are first washed with de-ionized water. a. Sterilization of Primary containers (Ampoules/vials): The primary conatiners are washed with de-ionized and/or distilled water and then sterilized in an electrically heated oven at about 250 0C. In some cases siliconaiztion to avoid sticking of materials is also done. b. Autocalving: all the dresses, equipment parts, gloves, glass containers etc are sterilized by autoclaving. c. Mixing and Filtration: Sterile liquid mixture is prepared by mixing active ingredients and excipients in the specified ratio . The liquid mixture is then filtered under sterile conditions. The distilled water is used for the washing of equipment, before starting the mixing and filtration processes. The filtration assembly is also sterilized prior to the process of filtration. c. Filling and Sealing: The ampoules/vials are filled with the liquid mixture and then sealed, on the automatic filling and sealing machine. d. Optical Checking: The filled ampoules/vials are subjected to visual inspection, under special light arrangement, to detect the presence of any particulate matter. The white particle are optically checked against black background and black against white background. e. Printing and Packaging: After checking ampoules/vials are sent for printing, on a printing machine. The final packing is done in packaging area. At the end the packed products are kept in big cartons and sent to warehouse for dispatch.
2.4.8 Capsule Manufacturing Process

This section presents typical process for the production of two-piece, hard gelatin capsules. The basic process in capsule manufacturing is the preparation of gelatin solution. Solution is processed in jacketed stainless steel melters equipped with stirrer. For transparent capsules, solution comprises of gelatin, water and some chemicals, whereas for the opaque capsules, titanium dioxide is added in the same solution as prepared for transparent capsules. Manufacturing of capsules is done in an electrically operated machine equipped with all necessary auxiliaries. The formation of capsule shape utilizes a precisionmachined set of moulds, to which the liquid gelatin adheres, forming both the cap and body sections. As the gelatin dries on pin, it hardens to form the capsule that is later
Page # 14
Production Process
removed from pin. Capsule shells are then subjected to cutting operation in a machine in order to obtain the required size. From here significant amount of cuttings of capsules are generated which are collected by vacuum in plastic bags. In Capsule Printing Machines, a conveyer belt carries capsules to the printing roller. Capsules are printed with words, logos and symbols that provide the desired identification of company and product. Printed capsules are shifted to the capsule sorting area, where they are manually sorted. Defective and approved capsules are separated. After sorting, the approved capsules are released for packaging. Capsules are packed either in aluminum foil bags or in heavy-duty Kraft paper bags as per the requirement of the customers.
2.5
Utilities
The main utilities in the pharmaceutical sector are water, electricity and fuels.
2.5.1 Water
Water is mainly consumed in the following activities: i. Process ii. Washing of equipment iii. Washing of bottles and ampoules iv. General washing of building areas v. Production of steam in boilers vi. Make-up water for cooling towers vii. Cooling medium in chillers for air-conditioning system viii.Quality control laboratory ix. Miscellaneous office uses Process water is de -ionized before use. De-ionized water is used for the following purposes: i. Washing of bottles and ampoules Creams and ointment manufacturing Quality control laboratory iv. Production of distilled water ii. iii.
Distilled water is used for injections and a variety of other medicines. Specific total and process water consumptions are estimated as 140-180 and 100150 liters per kg of raw ingredients, respectively. The process water does not include the sanitary water originating, being used for office use and general floor washings.
Page # 15
Production Process
2.5.2 Electricity
The electricity is used for the following purposes, in the pharmaceutical plants: a. Process and ancillary equipment b. Lighting, air conditioning and forced ventilation c. Pumps and compressors Specific electricity consumption is estimated as 10-20 kWh per kg of raw ingredients.
2.5.3 Fuels
The natural gas is mainly used in boilers and general office use. Diesel is the most common
fuel for standby generators and incinerators.
Page # 16
3
Environmental Issues and Impacts
Key environmental issues, associated with the pharmaceutical industry, are as follows: Wastewater Pollution Air Emissions Process Solid Waste Noise Pollution
This chapter presents the key environmental issues of the pharmaceutical sector and their environmental impacts.
3.1 Wastewater Pollution

Wastewater pollution is the main environmental issue of the pharmaceutical sector. Though the wastewater discharged is small in volume; but it is highly polluted, because of presence of substantial amounts of organic pollutants.
3.1.1 General
a. Biochemical Oxygen Demand (BOD): Biochemical oxygen demand (BOD), of wastewater, measured in mg/l, is the amount of oxygen, required by the microorganisms, for biochemical oxidation, of the organic matter. It is the most widely used measure of the organic pollution of the wastewater. Commonly used parameter is BOD5 that is BOD exerted in 5 days, at a temperature of 200C. b. Chemical Oxygen Demand (COD): Chemical oxygen demand (COD), of wastewater, measured in mg/l, is the amount of oxygen, required, for the chemical oxidation, of the organic matter. COD/BOD Ratio reflects the biodegradability potential of the wastewater. Generally, its value is higher for the industrial wastes than for the domestic waste.
3.1.2 Wastewater Sources and Quality

Table 3.1 presents summary of the wastewater generation sources and associated qualitative characteristics, from a typical pharmaceutical plant. The production processes, in general, are ba tch type and the consequent discharges are periodic in nature.
Page # 14
Table 3.1 Typical Wastewater Generation Sources and Qualitative Characteristics Pharmaceutical Plant Wastewater Washing of Process Equipment and Vessels Washing of Ampoules Cleaning and Washing of Floors Laboratory Wastewaters Periodic Discharge of Boiler Blow-down Water Steam Condensate Periodic Discharge of Cooling Tower Blow-down Water Backwash Water from Water Softeners Office Use & Miscellaneous
Source: ETPI Survey
Characteristics BOD, COD, SS, DS Clean Stream BOD, COD, SS, DS BOD, COD, SS, DS DS Hot Clean Stream DS DS BOD, COD, SS
A brief description of the wastewater generation mechanisms follows: a. Washing of Process Equipment and Vessels: This is the major source of polluted wastewater from pharmaceutical plants. In some units, the portable and mobile equipments or parts of the equipments are washed in a separate washing areas, while the fixed equipment is washed at its place. In general, the equipment are first washed with tap water and then with hot water to ensure its complete decontamination. Detergents are used as cleaning agents. Finally the equipment are dried by blowing compressed air. The autoclaves and tablet coating machines are generally washed with caustic solution after the completion of batch. b. Washing of Ampoules: Glass ampoules for injections are generally first washed with tap water, then with de -ionized water and final washing is done with distilled water. c. Cleaning and Washing of Floors: The floors of process area are generally first cleaned by vacuum cleaners to collect the dry materials and then mopped in case of spills. Occasionally the floors are washed with water. The floor washing wastewater contains traces of the spilled chemicals. Also the wastewater, generated from the washing of brooms, contains spilled materials. d. Laboratory: The wastewater generated from the laboratory is mainly due to the washing activities of laboratory utensils and accessories, which are contaminated with solvents, laboratory reagents and pharmaceutical chemicals.
Page # 18
e. Boiler Blow-down: In general, total dissolved solids (TDS) are not allowed to exceed 5000 mg/l in the boiler water. Higher TDS, due to their baking potential, reduce the heat transfer efficiencies of the boiler. In order to control TDS in the boiler contents, a part of the boiler water is discharged, periodically. The operation is called blow-down. The blow-down water is high in TDS and also contains residual chemicals used for boiler water conditioning. Temperature of blow down water is as high as 100 0C. f. Steam Condensate: Steam is used for autoclaves, tablet coating machines, distillation units, centralized air-conditioning and dehumidification systems and heating of jacketed process vessels. Steam after transferring heat becomes condensate. In cases, where there is no arrangement for collection and reuse of steam condensate, it is discharged as a wastewater. g. Cooling Tower Blow down: Cooling towers are provided, where centralized air conditioning systems are installed. To prevent the corrosion and scaling problem in the cooling water system, intermittent blow down is usually carried out. To makeup this loss, the level in the cooling tower is maintained by makeup water. This wastewater is high in TDS and also contains residual chemicals used for cooling water conditioning. h. Water Softener: Generally cation-exchange type softeners are being used by the local industry for production of soft water, for boiler feeding. Water softening media needs to be regenerated, periodically at an average interval of 24-48 hours, by back washing with high-strength sodium chloride solution. The wastewater generated in this process is very high in TDS and salt contents.
3.1.3 Wastewater Quantities

Unit total wastewater quantity including the sanitary wastewater originating from office use, floor washings and general cleaning operations is estimated as follows: Medicine formulation 120-160 liters/Kg of raw ingredients
Since a significant part of the wastewater results from periodic discharges from batch processes, with varying discharge intervals, the wastewater flow rates would show a relatively higher level of daily and seasonal fluctuations.
3.1.4 Wastewater Characteristics

a. Variation in Characteristics: Following aspects are of significance, while characterizing the wastewater generated by the pharmaceutical industry: i. Temporal Variation in Wastewater Characteristics: As has already been mentioned, the polluted process wastewater, mainly, results from periodic washing of various types of process equipment and vessels. This factor, in addition to the flow variations, also, results into relatively higher temporal, daily as well as seasonal, fluctuations in the characteristics of the wastewater. Another factor, which may contribute to large temporal variations, is processing of raw pharmaceutical ingredients, different types and chemical natures, at different times.
Page # 19
ii.
Plant to Plant Variations: The process wastewater characteristics may show a lot of variation, from plant to plant, depending primarily upon the types and natures of raw pharmaceutical ingredients, being processed.
The above factors make it difficult to establish a well-defined range for quality characteristic s of pharmaceutical wastewater. The characteristics, therefore, given in the following section shall be taken as indicative only. b. Composite Wastewater Characteristics: Important pollutants encountered in the wastewater from a typical pharmaceutical plant are organic pollutants (represented by BOD and COD), suspended solids (SS) and dissolved solids (DS). Table 3.2 presents some typical data on composite wastewater characteristics, from different pharmaceutical plants. Applicable National Environmental Quality Standards (NEQS) values are also given for the purpose of comparison. Table 3.2 Composite Process Wastewater Characteristics Parameters pH BOD5 COD Total Suspended Solids (TSS) Grease & Oil Sulfide (S) Phenols
Source: ETPI Survey, 2001
Unit mg/l mg/l mg/l mg/l mg/l mg/l
Typical Concentrations 6.0-7.5 300-400 400-800 200-600 0-13 0-50 0-1.5
NEQS 6-9 80 150 200 10 1.0 0.1
The above tabulated quality characteristics reveal the following: i. The characteristics show significant variation from plant-to-plant and sampleto-sample, due to the factors already mentioned in Section (a) above. BOD and COD values of the composite wastewater exceed the NEQS values, whereas TSS and oil & grease may exceed in certain cases. Sulfides and phenols may also exceed NEQS. The variation could be very drastic depending upon the process condition.
ii.
iii.
3.1.5 Impacts Associated with Wastewater

Impacts associated with the pharmaceutical plants wastewater pollutants, exceeding NEQS, are given in Table 3.3.
Page # 20
Table 3.3 Environmental Impacts of Wastewater Organic Pollutants Suspended Solids Depletion of the dissolved oxygen (DO) levels, of the receiving water body, below limits necessary to maintain aquatic life (4-5 mg/l). Sedimentation in the bottom of water bodies covers the natural fauna & flora on which aquatic life depends. Localized depletion of dissolved oxygen in the bottom layers of waters bodies. Reduced light penetration in natural waters and consequent reduction in photosynthesis Aesthetic nuisance Reduced re-aeration in the natural surface bodies, because of floating oil & grease film and consequent depletion in dissolved oxygen levels Reduced light penetration in natural waters and consequent reduction in photosynthesis. Aesthetic nuisance Nausea and gastric pains, in human beings, by ingestion of alkali sulfides Fish mortality at high concentrations (10 mg/l) Crown corrosion in public sewers by microbial production of sulfuric acid
Oil & Grease
Sulfides
3.1.6 Disposal of Wastewater

In most of the units, domestic and process wastewater is collected in separate sewerage lines but before final disposal these two streams are combined and the combined effluent is either treated in a wastewater treatment plant or disposed off directly to the municipal drain. Most of the Pharmaceutical industries treat their effluent in septic tank. The septic tank is viable for domestic wastewater because its function is to separate the sludge from the effluent which undergoes partial treatment under anaerobic condition. The baffles in the septic tank enhance the separation of water from the sludge and the clear water is thus drained. Some of the premier industries are endeavoring to slash the concentration of pollutants in their wastewater through wastewater treatment plant. The treatment system is based on activated sludge system. In this treatment system wastewater is treated by micro organisms (activated sludge) under aerobic condition. Main unit operations of the system are aeration tank, degasifier, settling tank and sludge silo.
Page # 21
3.2 Air Emission

3.2.1 Major Sources, Processes and Qualitative Characteristics of Air Emissions
Broadly the air emissions can be classified as point and diffused emissions. Point emissions are mainly from stacks and exhausts. Emissions from these sources can be quantified and easily monitored. Diffused emissions are those, which do not come through stacks or any exhaust and generally get directly into the occupational atmosphere of the production areas. Table 3.4 shows the important sources, operations, mechanisms of emission and the major potential pollutants in the emissions, of pharmaceutical industry. Table 3.4 Air Emission Sources/Operations and Major Pollutants Source/Operation Point Emissions Exhaust of Power Generators Stacks of Boilers Mechanism Combustion (Diesel) Combustion (Gas or Oil) Majo r Pollutants PM, CO, SOx, NOx PM, CO, SOx, NOx
Diffused Emissions Powdered & Granular Materials Processing Emissions of Dust Printing Operations Evaporation of solvents
PM VOC
Brief description of main diffused air emissions sources is as follows: a. Powdered and Granular Materials Processing: Pharmaceutical formulation industry carries out processing of a variety of pharmaceutical ingredients, which are in powder and granule form. Handling and processing of such materials may lead to emissions of particulate matter, into the occupational atmosphere of processing areas, in cases of inadequate coverage of processing equipment and absence or insufficiency of local or spot ventilation systems. Quantum of particle dispersion would depend also upon the particle size and liquid contents of the ingredients and the extent of agitation induced during the process. In general, the PM dispersion rate would be more in powder formulations than in granule. Depending upon the characteristics of ingredients and the ambient temperatures, some fumes may also get released, during the process. Following are some of the specific processes and operations, of pharmaceutical plants, which may cause dispersion of particulate matter, in the processing areas. i. Raw Ingredients Dispensing Operations: In dispensing areas, weighing of the pharmaceutical ingredients is carried out for their dispatch to the manufacturing area, in
Page # 22
specified quantities. Most of the ingredients handling operations are carried out manually. Generally open weighing machines are equipped with dust collectors. Steroids are liquefied in the dispensing area, by addition of solvents. Steroids and solvents also have a tendency to emit fumes and vapors. Particles and fumes dispersion into the working air takes place, where spot ventilation is inadequate or its operation is ineffective. ii. Milling Operation in Tablet Manufacturing: As described in Chapter 3, during tablet manufacturing dried granules, in some cases, are ground in a mill, for obtaining uniform particle size, prior to their compression into tablets. Milling machine is equipped with a spot dust collector. Dust emissions to the working air are excessive, where spot ventilation is ineffective. iii. Feeding of Powdered and Granular Ingredients into Open Process Vessels: In a number of formulation processes, powdered or granular ingredients are fed manually to the open blending and mixing vessels. Pouring of these materials, generally, generates significant amount of emissions, which go into the ambient air. iv. Encapsulation Process: In some old encapsulation machines, significant emissions of particulate matter take place during the capsule filling operation. The dispersion to the working air are excessive, where spot ventilation is ineffective. b. Printing Operations: A number of printing operations are carried out in a typical pharmaceutical formulation plant. Solvents, used in the printing inks, are in general volatile and vaporize into the atmosphere. The emission quantities of vapor mainly depend on the characteristics of the solvent and the ambient temperatures. The common solvent used in inks for the printing of tags and labels is methyl ethyl ketone. Ethanol-based inks are commonly used for printing on the capsules, in capsule manufacturing plants. The smell of these vapors is generally felt in the printing areas. Effective spot ventilation however results in significant reduction in the presence of vapors in the atmosphere.
3.2.2 Existing Situation on Point Emissions

Measured concentrations of various pollutants in samples drawn from some stacks of standby power generators (diesel) and boilers (fuel gas or furnace oil), of pharmaceutical industry, reveal the following: a. Oxides of nitrogen and sulfur are within NEQS limits, in most of the cases. In some cases they exceed the NEQS values.
Page # 23
b. Carbon monoxide, in most of the cases, exceed the NEQS values. In some cases, it is found to be as high as 20 times the NEQS limiting value. c. Relative concentrations of oxygen (O 2), carbon monoxide (CO), carbon dioxide (CO2) and hydrocarbons (HC), in the exhaust, indicate trends of incomplete combustion in some generators and boiler.
3.2.3 Existing Situation on Diffused Emissions

Most of the pharmaceutical plants have a combination of local or spot and area ventilation systems, in the processing areas. Spot forced ventilation systems capture emissions at the source, whereas area ventilation of the production areas is carried out, to continuously replace the working air, with the fresh air. It need be realized that, because of their capability to arrest and capture the emissions at source, local or spot ventilation systems are much more economical, practicable and viable, as compared to the general area ventilation systems, to control the occupational air pollution. For given emission rates at the source, the concentration of pollutants in the occupational air would primarily be inversely related to the collection efficiency and effectiveness of the local ventilation systems. The efficiency of the general ventilation of the area would also influence the pollution level in the working air. In practice, however, spot ventilation systems become quite ineffective, where distances of the suction inlet points from the sources of emissions are more than those desirable. This aspect is discussed in more details, in Chapter 4. Similarly, where ventilation systems are provided with in-built filters, to clean the air; clogging of these filters leads to reduction in the air flows, and consequently, to a decrease in the emissions capturing capacity of the system. Inadequate functioning of the spot ventilation system, results in dispersion of emissions in the working areas. No data are available on the occupational air quality of the production areas of the pharmaceutical plants. The design as well as operational efficacy and adequacy of the existing local and general ventilation systems, can not be established, therefore, on a reliable basis. However, it was observed that in most of the units, the air handling system was not working appropriately. Some of the problems are mechanical and some are in terms of organization.
3.2.4 Impacts of Air Pollutants on Environment and Human Health & Life
Impacts of common pollutants found in the air emissions from pharmaceutical plants are given in Table 3.5. Table 3.5 Impacts of Air Pollutants on Environment and Human Health & Life Particulate Matter E Damage to plants, by choking the leaf pores and restricting photosynthesis
Page # 24
Global cooling of earth by reflecting back the solar radiation Impairment of atmospheric visibility effecting transportation safety Deterioration of aesthetic quality of atmosphere, land and water. Soiling of materials, physical properties and infrastructure Carbon Monoxide HL Increase in the frequency of respiratory infections such as bronchitis HL Heart attack, by reducing the oxygen carrying capacity of blood Birth defects including mental retardation and impairment of fetus growth Dizziness, head ache and nausea Increase in reaction time of the drivers, a threat to the road safety Oxides of Sulfur E Chlorosis and plasmolysis in plants Damage to materials and property, by acid rains, resulting from oxidation of sulfur dioxide to tri-oxide to sulfuric acid, after reacting with water vapors. HL Serious lung damage, particularly in sulfate form Respiratory diseases like Chronic bronchitis E Formation of photochemical oxidants Damage to materials and property, by acid rains, resulting from oxidation of oxides of nitrogen to nitric acid, after reacting with water vapors. Retardation of grow th in plants HL Reduction in oxygen carrying capacity of blood Impairment of olfactory sense and night vision Dryness and roughness of the throat VOC Photo Chemical Oxidants E Formation of photochemical oxidants Leaf discoloration and cell collapse in plant Damage to rubber, textiles, paints and other materials HL Severe eye, nose and throat irritations Severe coughing and shortness of breath E Impacts on Environment HL Impacts on Human Life and Health
Oxides of Nitrogen
3.3
Process Solid Waste and Waste Chemicals

There are two broad categories of process solid waste generated in a typical pharmaceutical plant:
Page # 25
a. Contaminated Process Solid Waste b. Non-contaminated Process Solid Waste
3.3.1 Contaminated Process Solid Waste and Waste Chemicals

Table 3.6 presents contaminated process solid wastes and waste chemicals, which are generated in a typical pharmaceutical formulation plant. The table also provides estimated unit generation rates, for some of the wastes. The generation rates are established on the basis of the past available data. Table 3.6 Contaminated Process Solid Waste and Waste Chemicals - Pharmaceutical Formulation Industry Waste Waste Chemicals and Solvents Expired or Rejected Medicines Spillage Cleaning Materials Bag Filters & Filter Dust Contaminated Glassware Contaminated Emptied Drums
Source: ETPI survey NA: Not available
Unit Generation Rate (% Of Raw Ingredients) 0.60-1.50 0.50-1.00 0.05-0.15 0.15-0.25 NA NA
A brief description of different types of waste follows. a. Waste Chemicals and Solvents: These include all the waste chemicals, solvents and pharmaceutical ingredients, which are collected from laboratory and production areas. b. Expired or Rejected Medicines: The pharmaceutical industries collect back the expired products from the market. Beside this the raw materials and products, which are rejected by the quality control departments, are separately collected. c. Spillage Cleaning Materials: Accidental leakages and spillages from raw ingredients drums, bottles, containers, process equipment and vessels and pumps are the sources of floor contamination. A general practice is that all these spillages are either wiped with cloth rags or cleaned with vacuum cleaner. Sawdust is also used to absorb the liquid spillages. Used cloth rags, dust from the vacuum cleaners and sawdust are collected separately and should be treated as contaminated waste. d. Bag Filters & Filter Dust: In some plants, cloth filters are placed in the closed loop spot and area ventilation systems, to clean the circulating air from particulate matter. With time, as the filters get clogged with the dust, these are either cleaned or replaced. The dust and waste filters are to be treated as contaminated waste, because the dust contains traces of the chemical ingredients.
Cleaner Production Program (CPP) Page # 26
e. Contaminated Glassware: Following types of contaminated glassware is generated: i. Emptied laboratory chemicals bottles ii. Damaged laboratory glassware iii. Damaged or rejected ampoules iv. Damaged or rejected bottles of medicines f. Contaminated Emptied Drums: Most of the solid and liquid raw pharmaceutical ingredients are received in drums. After emptying, these drums still contain some residual material.
3.3.2 Existing Disposal Practices of Contaminated Solid Waste

Usually, the waste chemicals and contaminated solid wastes are being incinerated in an on-site or off-site facility. Incineration, under properly controlled conditions, is at present considered to be an appropriate method for the disposal of waste chemicals and contaminated solid waste, of pharmaceutical industry.
Some of the progressive units have installed their own in-house incinerators. One such incinerator is a multistage unit, comprising primary, secondary, and settling chamber, for incineration of all types of waste chemicals and contaminated solid waste. In primary or ignition chamber, material is charged and allowed to burn at 500-8500C. The secondary chamber or after burner allows the combustion of gases, at temperatures of about 1,000-1,200 0C. Ash and other noncombustible residues are collected in the settling chamber. The ash, which is obtained after incineration, is immobilized by fixation in cement concrete blocks. Some of the units are using of-site commercial facilities for incineration of their contaminated waste. The performance of the above incinerators cannot be evaluated because monitoring data on the quantum and quality of the air emissions and residue ash contents, along with the quality and characteristics of corresponding feed materials are not available. Some of the local industries are practicing open burning of their contaminated waste. Due to uncontrolled burning, fumes and chemicals of the pharmaceutical chemicals, dispersed in the community air which can pose very serious health hazards to the people. Some of the industrial units have installed glass shredding machines, to crush the contaminated glassware, to prevent their direct reuse. The crushed glassware is then dispatched to the contractor for recycling or disposal purposes. To prevent the direct reuse of contaminated empty drums, some industrial units have installed hydraulic presses, for damaging these. These deformed drums are then sold to contractor for their recycling.
Page # 27
3.3.3 Non-contaminated Process Solid Waste

Table 3.7 presents non-contaminated process solid wastes, which are generated in a typical pharmaceutical formulation plant. The table also provides estimated unit generation rates, for some of the wastes. The generation rates are established on the basis of the past available data. Table 3.7 Non-contaminated Process Solid Waste Pharmaceutical Formulation Industry Waste Corrugated Cartons Poly bags Fiber Drums Wooden Pallets Iron Scrap Non-contaminated Glassware Non-contaminated aluminum cans Damaged and rejected labels
Source: ETPI survey NA: Not available
Unit Generation Rate (% of Raw Ingredients) 5.0-10.0 % 1.5-2.5 % NA 4.0 % 0.1 % NA NA 4.0 %
Most of the above-tabulated wastes are sold to the contractor for reuse or recycling by the downstream users. In specialized capsule manufacturing units, major process solid wastes are rejected capsule shells and cuttings and a variety of packaging materials. Rejected capsule shells and cuttings are estimated as 10% of the product, by weight.
3.4
Noise Pollution
3.4.1 Noise Sources and Levels

Table 3.8 presents ranges of noise levels, measured at a distance of 7.5 meters from some of the process and ancillary equipment, used in the pharmaceutical plants. Permissible noise level limit, as promulgated by NEQS, is 85 dB-A.
Table 3.8 Typical Noise Levels in Pharmaceutical Industry Equipment (Noise measured at 7.5 meters from Source) Noise Levels (dB-A) Tablet Compression Machine 80-84
Page # 28
Capsule Manufacturing Machine Grinder Glass Shredding Machine Chillers for HVAC System Electricity Generators (Diesel)
Source: ETPI survey
87-89 106 95 110 102-120
3.4.2 Potential Impacts of Noise Pollution

Noise is considered as an interference to and imposition upon comfort, health and the quality of life. Noise may have both physiological as well as psychological effects on human beings. Physiological effects include dizziness, nausea, unusual blood pressure variation, physical fatigue, hearing impairment and, in acute cases, permanent hearing loss. The psychological effects may comprise reduced mental capability and irritations. Chronic exposure of workers to higher noise levels also impairs their efficiency and skill.
Page # 29
4
Recommendations
This chapter lays down general recommendations, on the following environmental issues of pharmaceutical sector: a. b. c. d. Wastewater Treatment Occupational Air Quality Control Contaminated Solid Waste and Waste Chemicals Management Occupational Health and Safety Measures
4.1 Wastewater Treatment

4.1.1 General
The following recommendations are applicable to the wastewater originating from pharmaceutical formulation plants. It is suggested that, in general, both the wastewater from office use and the process wastewater shall be combined for the purpose of treatment.
4.1.2 Wastewater Quantities

It is suggested that prior to going for the implementation of wastewater treatment, the industrial unit shall carry out detailed flow monitoring and characterization of the wastewater. In the absence of such data, however, the unit wastewater quantities, laid down in Section 3.1.3, may be used for establishing wastewater flows, for preliminary analysis and design.
4.1.3 Wastewater Characteristics and Effluent Quality Standards

As already mentioned in Chapter 3, the composite wastewater characteristics may vary from plant-to-plant and day-to-day, depending mainly upon the type of pharmaceutical ingredients being processed. In Table 3.2 of Chapter 3, some typical data on composite wastewater characteristics, based on field sampling and laboratory measurement, from different pharmaceutical plants is presented. Table 4.1 presents expected maximum-day composite wastewater characteristics of pharmaceutical formulation plants. Required degrees of treatment, to meet the National Environmental Quality Standards (NEQS), are also established. Table 4.1
Page # 30
Recommendations
Maximum Day Composite Wastewater Characteristics and Required Degree of Treatment Pharmaceutical Formulation Plant Parameter Unit Expected Values 6.0-7.5 Mg/l Mg/l Mg/l Mg/l Mg/l 300-400 400-800 0.40-0.75 200-600 0-50 0-1.5 NEQS [1] Required Degree of Treatment (%) 73-80 63-80 0-67 0-98 0-93
Value of pH Biochemical Oxygen Demand (BOD) Chemical Oxygen Demand (COD) BOD/COD Ratio Total Suspended Solids (TSS) Sulfide (as S) Phenols
[1] NEQS for disposal to Inland Waters
6-9 80 150 200 1.0 0.1
Organic pollutants, represented by BOD and COD, are the principal pollutants. BODtoCOD Ratio ranges from 0.4 to 0.75, which shows that wastewater is highly biodegradable and would respond effectively to the biological treatment. In some plants sulfides and phenols are present in very high concentrations in the wastewater. In such cases, wastewater will also require treatment for their removal.
4.1.4 Proposed Wastewater Treatment System for Removal of Organic Pollutants

a. Proposed Treatment Process: Extended aeration activated sludge process is being commonly employed for the treatment of combined wastewater from pharmaceutical formulation plants. The system is contrasted from the conventional activated sludge process, by relatively low food-to-microorganism ratios and longer retention periods. The sludge production is less as compared to conventional activated sludge process. The system, due to longer hydraulic retention periods, can absorb pollution load fluctuations and is relatively easy to operate and monitor, as compared to the conventional activated sludge process. The biological treatment is carried out by forced supply of air to the wastewater in the aeration tank, where a contact, in suspension form, is maintained between microorganisms (activated sludge) and the incoming wastewater. The aerated effluent is then allowed to pass though a secondary clarifier to separate the biomass or the activated sludge. A part of the "activated sludge", removed in the secondary clarifier, is recycled to the aeration tank to maintain optimum microorganism concentrations. The remaining secondary sludge is removed from the system periodically. The waste sludge received is reasonably stabilized and does not generally require any further treatment, except for de -watering and drying, for reduction in its volume. The waste sludge can be dewatered and dried on sludge drying beds or in sludge filter press. In case of sludge filter press, a sludge thickener shall also be installed before the filter press.
Page # 31
Recommendations
The sludge, in case of pharmaceutical plants, shall be treated as contaminated solid waste and be incinerated. Excess sludge can also be directly incinerated without any dewatering; but this will incur very high operational costs. Incineration of sludge after dewatering and drying is suggested. Pharmaceutical wastewater may, sometimes, contain substances, which are toxic to the microorganisms. Presence of such substances may inhibit the microbial growth, required for the proper functioning of the activated sludge process. In such cases, toxicity of wastewater can be controlled by addition of powdered charcoal in the aeration tank. Charcoal exhibits excellent potential for adsorbing a variety of toxic organic chemicals. Required dosages can be established by carrying out laboratory scale studies. The charcoal particles would be removed from the wastewater in secondary clarifier, along with secondary sludge.
b. Performance of Existing Treatment Systems: Measured treatment efficiencies, of an existing wastewater treatment plant, based on extended aeration activated sludge plant, with aeration period of about 32 hours, for a pharmaceutical formulation industry, are given in Table 4.2. Table 4.2 Treatment Efficiencies Based on Composite Wastewater Characteristics Existing Extended Aeration Activated Sludge Plant (Pharmaceutical Formulation Plant) Parameter Unit Influent Effluent Treatment NEQS [1] Efficiency (%)
Page # 32
Recommendations
Value of pH Biochemical Oxygen Demand (BOD) Mg/l Chemical Oxygen Demand (COD) Mg/l Total Suspended Solids (TSS) Mg/l Anionic Detergents (as MBAS) Mg/l [1] NEQS for disposal to Inland Waters
7.5 223 452 140 4.0
7.7 29 53 27 2.2
87 % 88 % 81 % 45 %
6-9 80 150 200 20
The results show that proposed process is capable of achieving a high degree of treatment. c. Treatment Facilities: Extended aeration activa ted sludge process in general shall comprise the following process facilities. Buildings (if required) and external works are not mentioned. i. Wastewater Screening and Pumping Station ii. Aeration Tank iii. Secondary Clarifier iv. Sludge Pumping Station v. Sludge Drying Beds or Sludge Thickening Tank + Sludge Press Filters d. Sulfides Removal: In some pharmaceutical formulation plants, sulfides are present in wastewaters in concentrations, much exceeding the NEQS limits and, therefore, need to be removed, prior to its disposal. In one example, these sulfides existed at pH of 6.2-6.8. In general, also, the pH values of the pharmaceutical wastewater are found to be in the close-to-neutral range of 6 to 7.5. Sulfides change their forms, in water mediums, with change in its pH value. The chemical balance of sulfides in wastewater is such that, at a pH value of 9, hydrogen sulfide (H2S) formation takes place. The concentration of hydrogen sulfide increases with decrease in pH and reaches to a relative concentration of 100% at pH of the order of 5. On the other side, at pH of 8, formation of alkaline and metallic sulfides takes place, which increase with the increase in the pH value. At pH value of 7, about 50% of the sulfides exist as hydrogen sulfide. It is expected that hydrogen sulfide present, in close-to-neutral or slightly acidic pharmaceutical wastewaters, would be stripped of and removed, consequent to forced aeration of wastewater, in activated sludge reactor. Stripping of hydrogen sulfide, from wastewater at an instant, would lead to formation of more hydrogen sulfide, to maintain the chemical balance. Extended aeration, for a period of the order of 24 hours, would result in a continuous chain reaction of formation and stripping of hydrogen sulfide. It is envisaged that in this way, required removal of the sulfides would be achieved, in extended aeration activated sludge process and in most of the cases, no separate treatment for removal of sulfides would be required.
Page # 33
Recommendations
e. Estimated Unit Costs of Treatment System: Unit capital cost of extended aeration activated sludge treatment system, with provision of sludge drying beds, including civil, mechanical and electrical works, for a pharmaceutical formulation plant, is estimated as Rupees 20,000 to 30,000 per kg/d of BOD load. Variation in the unit capital cost of the treatment systems principally reflects the factor of economy of scale or size of the treatment system and extent and quality of the electro-mechanical equipment installed. Due to the fixed cost factors, however, the capital cost of the smallest plant would not be less than Rupees 2.00 million. Unit annual operation and maintenance (O&M) cost (excluding the dried sludge incineration cost) is estimated as Rupees 10 to 15 per kg of annual BOD load, with a minimum total annual O&M cost of Rupees 250,000.
4.1.5 Activated Carbon Adsorption Treatment for Removal of Phenols

In some pharmaceutical wastewaters, phenols are found to be present, in concentrations exceeding the NEQS values and treatment would be required for their removal. Activated carbon is very effective for removing a number of dissolved organic chemicals, by process of chemical adsorption. In this system, wastewater is filtered through an activated carbon filter. After a period of use, depending upon the total pollution load of dissolved organic compounds removed by the filter, the activated carbon media gets exhausted and becomes ineffective. The spent media shall then either be replaced with fresh activated carbon or alternatively it can be reused after regeneration. One most commonly used method of exhausted activated carbon regeneration is its incineration at high temperatures. In order to maximize the effectiveness of the activated carbon adsorption, it is suggested that, where required, this treatment shall be carried out after activated sludge process.
4.2
Occupational Air Quality Control
As already described in Chapter 3, the major process related air emissions, to the occupational air, in a typical pharmaceutical formulation plant, which can affect the occupational air, are as follows: a. Emissions of Particulate Matter from Processing of Powdered and Granular Materials i. Raw Ingredients Dispensing Operations ii. Milling Operation in Tablet Manufacturing iii. Feeding of Powdered and Granular Ingredients into Open Process Vessels Encapsulation Process b. Emissions of Vapors from Printing Operations
iv.
Page # 34
Recommendations
The process of controlling the occupational air quality comprises the following sequential steps: a. Establishing the occupational air quality criteria, need to be maintained, for the protection of the health and safety of the workers. Main features of the criteria are described in Annexure I. b. Planning, designing, installation and operation of a comprehensive system, which ensures maintenance of the occupational air quality, within the desirable limits. Such a system would comprise the following components: Enclosure of the emission sources, where possible Local or spot ventilation system General area or room ventilation system Personal protection
c. Continuous monitoring of the occupational air and other related parameters, to check and ascertain that the intended air quality is being achieved. The recommendations, on the above-mentioned steps, applicable to the production areas of pharmaceutical industry, follow:
4.2.1 Enclosure of the Emission Sources

As far as practicable, the medicines formulation and filling equipment, involving processing of powdered, granular and vaporizing ingredients, should be enclosed. If emissions to working area can be reduced by a better enclosure, this should be introduced first. Such enclosures also help improve the performance and effectiveness of the spot ventilation system.
4.2.2 Criteria for Local or Spot Ventilation System

The purpose of spot or local ventilation system, in industrial production areas, is to capture and arrest the vapors, fumes and particulate matter, at the source of their emissions, before they get dispersed to the working air. Such systems are highly economical, practicable and viable, as compared to the general area ventilation, to control the occupational air pollution. For certain emission rates at the source, the concentration of pollutants in the occupational air would primarily be inversely related to the collection efficiency and effectiveness of the local ventilation systems. Following criteria and guidelines may be used by the pharmaceutical industry, for the design of local ventilation system. Values of various parameters, as suggested in following paragraphs, may, however, be changed in the light of on-site observations and experiential information. a. General
Page # 35
Recommendations
Local ventilation system shall mainly comprise collection hoods, air transmission ducts, exhaust-air blowers and pre-emission or pre-circulating air treatment system. All the localized vapors, fumes or particulate matter emission sources, in the process areas, should be provided with spot ventilation. Substantially enclosed units should also be provided with the fresh air supplies.
b. Clear Face Distance of Collection Hood : The hood face should be as close as possible to the source of emission, keeping in view the other installation and operational requirements and constraints. This principle is of utmost importance, because inward air velocities, towards a suction opening, drop at a drastic rate, with respect to the distance from the suction opening, as shown in Equation 4.1. c. Capture and Face Velocities: Required capture velocities shall be maintained at the emission source. Required minimum capture velocities are given in Table 4.3. Table 4.3 Range of Capture Velocities for Dusts, Vapors, and Fumes Condition of dispersion of Contaminant Examples Capture Velocity (m/min) 15-30 30-60
Released with practically no velocity into Evaporation quiet air Released with low velocity into moderately Intermittent still air container filling Active generation into zone of rapid air Grinding motion
60-150
The capture velocities, for different process, may be established on the basis of on-site observations and experiential information, in the light of Table 4.2. Equation 4.1 shows the relationship between velocity at the hood face and inward velocity at a distance X from the face and can be used for determining the required face velocity from the already established capture velocity, at the source. Ve ------------------{(10X2/A) + 1}
V=
(4.1)
Where V = Centerline air velocity at X distance from the hood face
Page # 36
Recommendations
Ve = Centerline air velocity at the hood face X = Outward distance from hood face along centerline axis A = Hood opening area d. Hood Opening Size: The opening size of the hoods shall mainly be function of the size of the emission opening and the distance of hood opening from it. The hood opening size shall be minimum possible to achieve the desirable capture efficiency, under given velocity conditions. e. Exhaust Air Flow Capacity: The discharge capacity of the exhaust air blower shall be the sum of the required flow rates, in all the suction hoods. The required flow rate for each hood shall be the product of its opening area and the face velocity.
4.2.3 Criteria for General Area or Room Ventilation System

In addition to the spot ventilation, general or room ventilation of the production areas shall be required to continuously replace the working air and to control the concentrations of particulates, being generated from non-point sources and those, not captured by the spot ventilation system. a. The exhaust-air flow capacity may be based upon the air dilution required to keep the pollutants concentration equal to the allowable concentration levels. Equation 4.2 and 4.3 are based upon this concept and may be employed for design of general ventilation system. Q= E= Where Exhaust air flow rate, m3/min Allowable pollutant concentration level in the working air, kg/m3 Pollutant emission rate to the working air, kg/min Pollutant emission rate from all diffused sources, without spot ventilation, kg/min Ep = Pollutant emission rate from all point sources, with spot ventilation, kg/min Y = Capture efficiency of the spot ventilation system Q= C= E= Ed = The above model is based upon the assumption that there is perfectly uniform distribution of the air and pollutants in the working area. Where actual conditions are far from this assumption, the above computed exhaust flow rate may be increased, by multiplying with a correction factor. b. Capture efficiency of a well designed and operated local ventilation system should be in the range of 80-85 %. E/C Ed + (1-Y) Ep (4.2) (4.3)
Page # 37
Recommendations
c. In case of emissions of a number of pollutants, the required exhaust-air flow rates should be determined for all the individual pollutants, separately, and the highest flow rate shall be taken as the ventilation capacity.
4.2.4 Monitoring
In order to ascertain that the desired occupational air quality is being maintained and further to assess the adequacy of the measures taken in this regard, a monitoring program should be implemented, as follows: a. Occupational Air Quality Monitoring: It is suggested that a comprehensive working air monitoring program shall be implemented, to ensure that toxic vapors and particulates are within the acceptable limits. Our recommendations in this regard are as follows: Working air sampling and laboratory testing, to establish occupational air concentrations for pollutants, shall be carried out on continuous basis at a specified interval. In the powder filling and granule units the levels of particulate matter (PM10) should also be monitored. The sampling shall cover the spatial variation. Sampling locations shall include both general areas and points close to the emission sources.
b. Ventilation System Monitoring: The monitoring of ventilation system shall mainly comprise measurements of the face velocities, for all the collection hoods, other suction openings, and fresh air inlet points. Comparison of the measured velocities with the design velocities shall indicate, whether the system is working at its design conditions or not.
4.2.5 Exhaust or Re-circulating Air Carrying Particulate Matter from Granule & Powdered Ingredients Processes
The exhaust air carrying particulate matter shall be treated with fabric bag filters. Fabric bag filters are considered to be high efficiency particulate removers. Under optimum conditions, a fabric filter can remove 99% of the particles of size above 1 micron. The fabric filters shall be cleaned or replaced, at intervals, to remove the dust. The exhaust filter and the dust shall be treated as contaminated solid waste. The efficiency of the fabric filters should be monitored and evaluated regularly on the basis of particulate matter in influent and effluent air streams.
4.3 Contaminated Solid Waste & Waste Chemicals and Management 4.3.1 Waste Segregation and Quantification
The major contaminated solid waste and waste chemicals, generated in a typical pharmaceutical formulation plant, as already described in Chapter 3, are summarized below: a. Waste Chemicals and Solvents b. Expired or Rejected Medicines c. Spillage Cleaning Materials
Page # 38
Recommendations
d. Bag Filters & Filter Dust e. Contaminated Glassware f. Contaminated Emptied Drums All the contaminated solid waste and waste chemicals should be segregated from other wastes and properly stored, till their disposal. It is recommended that even different categories of these wastes should be segregated at source and stored in separate stacks. The quantities, generation rates and pertinent characteristics, of the wastes produced, in each category, should be regularly measured and documented. This data would be helpful in proper planning of the waste disposal operations.
4.3.2 Prevention of Waste Generation

Possible reduction of waste should always be the first measure, to be considered. This could be achieved by proper training of workers, creating awareness on reduction in waste generation and setting practicable limits on amount of waste produced.
4.3.3 Storage of Contaminated Waste and Waste Chemicals

All the contaminated solid waste and waste chemicals shall be stored under safe and controlled conditions. No spillage shall take place in case of liquid wastes. The wastes storage times should be as less as possible. All the boxes and containers of contaminated waste should be properly labeled, with warning signs.
4.3.4 Contaminated Waste Treatment and Disposal by Incineration

It is recommended that low -temperature open burning of the contaminated solid wastes shall not be practiced. Because the fumes and vapors of the pharmaceutical chemicals, dispersed in the community air, can pose very serious health hazards to the people. Incineration is, at present, considered to be a suitable technology for the disposal of waste chemicals and contaminated solid waste, of pharmaceutical industry. It is the controlled thermal oxidation and decomposition of organic matter, at very high temperatures. Incineration process, if operated at proper temperatures, residence times, and turbulence levels, result into a very high destruction of the Principal Organic Hazardous Constituents (POHC), by their thermal degradation. Waste material is ultimately converted into combustion gases and ash. a. Contaminated Waste Incinerator: Incinerators, of different types, are available in small to very large sizes. Generally, provision of a proper in-house incineration facility would not be economically feasible for most of the pharmaceutical units, with the kind of contaminated waste loads encountered; because the incineration capacities of even the smaller size commercially available incinerators are much more than those required by most of the typical individual units and the capital costs of duly equipped incinerators are quite high.
Page # 39
Recommendations
It is suggested to look into the possibility of installation and operation of the required properly equipped incineration facilities, with the provision to run the facility, on commercial basis, for incineration of similar waste from other pharmaceutical units as well as for the hazardous wastes from other industries, under one of the following arrangements: Individually by one or more larger pharmaceutical units Jointly and collectively by a group of the pharmaceutical industrial units By Pakistan Pharmaceutical Manufacturers Association (PPMA)
Suggested contaminated waste incinerator, for the pharmaceutical industry, is rotary kiln type, which can simultaneously incinerate solid as well as liquid contaminated wastes. It shall comprise rotary kiln (primary combustion chamber), an afterburner (secondary combustion chamber), exhaust Air Pollution Control System (APCS) and necessary instrumentation for control of incineration process and air quality sampling and monitoring. The highest temperatures to be maintained in the kiln and after- burner should be of the order of 850 0C and 1200 0C, respectively. Solid waste shall be fed to the kiln and the liquid wastes to the after-burner, injected through an atomizer, to convert the liquid into droplets as small as one microgram. The system shall be provided with a blower of appropriate size to force air into it to increase the combustion efficiency and produce turbulence. Both the kiln and after-burner shall have provisions for introducing supplementary fuel. A typical Rotary Kilin is shown in the figure 4.2.
Figure 4.2 Rotary Kilin
The function of Air Pollution Control System (APCS) shall be to cool and clean the emitted gases. The APCS shall be capable of bringing the quality of emission gases within the applicable NEQS limits, for the worst type of waste anticipated. b. Operational Aspects Control of incineration Process
Cleaner Production Program (CPP) Page # 40
Recommendations
Empirical tests, in form of trial burns, shall be carried at the time of commissioning, to establish the operational Destruction and Removal efficiency DRE. Flue gas should be analyzed, for particulate matter (PM), carbon monoxide (CO), oxygen (O 2), and for oxides of sulfur & nitrogen (only if they are expected to be present in any quantity), during the trial burn. Following parameters should be continuously monitored to ensure that DRE is maintained at the levels achieved in the trial burn: Temperatures in the primary and secondary chamber Oxygen in the stack Stack gas volume flow
Emissions Sampling and Monitoring: The air emissions should be monitored for the applicable parameters, to check their conformity to the NEQS. Disposal of Residue Ash: The ash should be analyzed for the concentration of the respective heavy metals, when they are expected to exist depending upon the nature of feed waste material. If the concentration of heavy metals is within the permissible limits, it may be disposed of on land. If the concentration is exceeding the safety standards for soil, the residue ash should be disposed of to a properly developed secure landfill.
4.3.5 Contaminated Glassware

All the contaminated glassware shall be shredded, prior to its dispatch to the market for recycling purposes. This practice is required to prevent a direct reuse of the glassware, by any downstream consumer.
4.3.6 Contaminated Emptied Drums

In order to prevent a direct reuse, by the downstream users, all the contaminated emptied drums should be crushed and then sold to the market, for recycling in the steel melting industry. The temperatures, of the order of 1500-1600 0C, encountered in the steel melting process, can totally destruct the traces of ingredients, adhering to the crushed drums. Use of a drum-deforming machine, instead of the manual crushing, should be preferable.
4.5 Occupational Health and Safety (OHS) Measures

Safety, health and hygiene hazards in pharmaceutical industry are higher and more focused than many other industrial processes. In order to improve the OHS condition, following specific and general measures are recommended.
4.5.1 Material Safety Data Sheets (MSDS) for Hazardous Substances
Page # 41
Recommendations
For all the hazardous substances, used in the unit, Material Safety Data Sheets (MSDS) should be prepared. The MSDS should be complete, up-to-date and in a language, that all people can understand, including the workers. These MSDS should be available at a central place as well as at places, where handling of the related chemical is being done.
4.5.2 Fire Fighting System

This section lays down some general recommendations on the fire fighting system requirements. Fire, in general, is grouped into four classes, according to the type of the burning material. Characteristics of these classes of fire and the applicable types of fire extinguishers are given below: a. Class A Fire Characteristics: It includes those fires in which ordinary combustibles such as wood, cloth, and paper are burning. Fire Extinguishing Mechanism: Class-A fire extinguishers are usually water based. Water provides a heat absorbing (cooling) effect on the burning material to extinguish the fire. b. Class B Fire Characteristics: These fires are those in which flammable liquids, oil, and grease are burning. Fire Extinguishing Mechanism: Class-B fires are put out by excluding air, by slowing down the release of flammable vapors, or by interrupting the chain reaction of the combustion. Three types of extinguishing agents, including carbon dioxide gas, dry chemicals and foam, are used. Carbon dioxide is a compressed gas agent that prevents combustion by displacing the oxygen in the air surrounding the fire. One type of the dry chemical extinguishers contains ordinary sodium or potassium bicarbonate, urea and potassium chloride base agents. c. Class C Fire Characteristics: These are the fires, which involve live electrical equipment. Fire Extinguishing Mechanism: The extinguishing agent for this class of fire should be electrically non-conductive. Both carbon dioxide and dry chemicals can be used in electrical fires. An advantage of carbon dioxide is that it leaves no residue after the fire is extinguished. When electrical equipment is not energized, extinguishers for class A or B fires may be used.
d. Class D Fire
Page # 42
Recommendations
Characteristics: These fires involve combustible metals such as magnesium, potassium and sodium. Fire Extinguishing Mechanism: A heat absorbing extinguishing medium is needed for fires in combustible metals. Also, the extinguishing medium must not react with the burning metal. The extinguishing agents, known as dry powders, cover the burning metal and provide a smothering blanket. A pharmaceutical unit may have to provide more than one type of parallel fire fighting systems, depending upon the specific materials and processes involved.
4.5.3 Personal Protection Equipment (PPE)

It is recommended to make arrangements for full coverage of employees with PPE. PPE inventory should be maintained and the used equipment should be replaced at suitable intervals. It is recommended to introduce a system based on rewards and penalties to ensure full use of PPE. Genuine problems in the inconvenience of use of PPE should, of course, be addressed to. In this regard, it is seen that maximum impact comes from demonstration effect whereby the top management themselves takes personal protection measures.
4.5.4 First Aid Medical Treatment

Following provisions shall be made in this regard: Providing first aid boxes in each department and keeping their inventory checks Carrying out workers training on attending to a medical emergency
4.5.5 Uniforms
Workers uniforms should be washed daily. Uniforms contaminated, with toxic ingredients, due to spillage should be discarded and treated as contaminated solid waste.
4.5.6 Trainings and Procedures

In order to minimize the possibilities of personal exposure to hazards and risks, the management and workers should be educated and trained on safe working practices. Following is a tentative list of the subjects on which awareness and training should be imparted to workers as well as to the management: a. b. c. d. e. f. Transport of products and handling in case of accident Safe storage and handling of chemicals Chemical leakage and spillage management Use of Personal Protection Equipment (PPE) General safety precautions General cleaning activities
Page # 43
Recommendations
g. Good housekeeping On all the aforementioned issues, where training is required, written procedures and instruction manuals should prepared and made available to the workers.
4.5.7 Records and Evaluation

Pharmaceutical units should maintain the following records, in order to help devise future remedial measures: Record of accidents, both in factory and during material transportation Records of illness and diseases of staff
4.6 Recommended Institutional Measures

Following institutional measures are recommended to the industries in pharmaceutical sector for improving the environmental and the occupational health & safety conditions.
4.6.1 Defining and Setting Objective and Policies

The top management shall define and set the short-term and long-term objectives and policies, on all the environment, health & safety (EHS) issues. Compliance with legislation and commitment to continual improvement should be the objectives, to be covered by an environmental policy statement. Environmental goals and objectives should be as specific and quantified as possible. The management shall establish Environment, Health & Safety (EHS) department, which shall be responsible for the planning, coordination, implementation and monitoring of the measures, identified in the light of the objectives and policies, set by the management.
4.6.2 Areas of Responsibilities of EHS Department

Following shall be the main areas of activities of EHS Department: a. b. c. d. e. f. g. h. j. k. l. m. Air & Water Quality and Noise Monitoring Air, Water and Noise Pollution Control Monitoring and Control of Malodorous Emissions Management of Solid Waste Implementation of Waste Minimization Programs Management of the Accidental Release of Pollutants Handling and Management of Toxic and Hazardous Substances Fire Fighting Monitoring and Control for Water Conservation Monitoring and Control for Energy Conservation Electrical Safety Monitoring and Control Monitoring and Control of Occupational Health and Safety
Page # 44
Recommendations
4.6.3 Functions of EHS Department

EHS department shall carry out the following functions in all of its areas of responsibilities: a. Defining roles, responsibilities and tasks of other departments and the staff, in the operation of the EHS management system. b. Setting applicable standards, guidelines and other regulatory requirements, in the light of local and international standards, pertinent statutory requirements and international treaties, agreements & covenants. c. Development of operational control procedures and manuals, for operation & maintenance of related equipment and works d. Establishing emergency procedures for providing rapid and effective action in the event of accidents that pose serious threats to the environment or to the surrounding community. e. Carrying out training to all the facility personnel for the following purposes: Creating and promoting general concern and awareness on EHS issues. Training in control, operation and maintenance of EHS equipment
f. Coordination with the concerned government agencies as well as any local community services, on EHS issues. g. Documenting and maintaining all the pertinent records and data. h. Setting up Environmental Monitoring System, for monitoring and evaluation of the environmental performance. j. Setting up Environmental Management System (EMS), preferably, in accordance with ISO 14001, which is the international standard for environmental management system, after a proper monitoring system has been developed. k. Implementation of the projects related to the EHS.
Page # 45

Report Pharma

Hochgeladen von

Dokumentinformationen

Originaltitel

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Report Pharma

Hochgeladen von

Copyright:

Verfügbare Formate

Pharmaceuti cal Sector

Preface Executive Summary

2.4 Typical Production Processes 2.4.1 Dispensing

Pharmaceutical Sector Report

2.4.2 2.4.3 2.4.4 2.4.5

9 10 10 10 2.4.6 Creams, Ointments

Cleaner Producti on Program (CPP)

Pharmaceutical Sector Report

4.1 4.1.1 4.1.2 4.1.3 4.1.4

4.3 4.3.1 4.3.2 4.3.3 4.3.4 4.3.5 4.3.6 4.5

Cleaner Production Program (CPP)

Pharmaceutical Sector Report

Cleaner Production Program (CPP)

Pharmaceutical Sector Report

Cleaner Production Program (CPP)

Cleaner Production Program (CPP)

Cleaner Production Program (CPP)

Page # Pharmaceutical Sector Report

Cleaner Production Program (CPP)

Cleaner Production Program (CPP)

Pharmaceutical Sector Report

Cleaner Production Program (CPP)

Pharmaceutical Sector Report

1.2 Overview of the Pharmaceutical Sector Environmental Report

Cleaner Production Program (CPP)

1.3 Pharmaceutical Sector of Pakistan

Cleaner Production Program (CPP)

Pharmaceutical Sector Report

Source: IMS 12 Mths data To Dec. 01

100 102 99 109 99 102

100.0 13.4 5.2 3.8 2.9 1.5

2,860 2,694 1,723 971 2,124 1,091 695 338

2.90 19.70 13.50 32.50 8.80 11.70 4.90 8.00

96 112 106 124 102 104 98 101

6.6 6.2 4.0 2.2 4.9 2.5 1.6 0.8

Pharmaceutical Sector Report

12 Mths data To Dec01

2.1 Raw Materials and Products

2.1.2 Raw Materials

Cleaner Production Program (CPP)

Main Production Facilities

2.2.1 Storage Facilities

Cleaner Production Program (CPP)

Pharmaceutical Sector Report

2.2.2 Manufacturing Facilities

2.2.3 Over Printing Area

Cleaner Production Program (CPP)

Pharmaceutical Sector Report

2.2.4 Packaging Area

2.3.1 Quality Control (QC/QA) Laboratory

2.3.2 Ventilation Systems

2.3.3 Chillers and Cooling Towers

2.3.4 Fire Detection and Fighting Systems

Cleaner Production Program (CPP)

Pharmaceutical Sector Report

2.3.6 Water Softening Units

2.3.7 Water De-ionizing Units

2.3.8 Water Distillation Unit

2.3.10 Hydraulic Press

Cleaner Production Program (CPP)

Pharmaceutical Sector Report

2.4 Typical Production Processes

2.4.2 Tablets Manufacturing