SECTION 3

3.1

PHARMA

LONG TERM IMPROVEMENT MEASURES (ABATEMENT OF RESIDUAL VOC EMISSIONS)

The measures discussed in Section 2.1 - 2.4 in terms of upgraded local condensation and improved VOC management will result in lower residual VOC emissions. The primary scrubbers discussed in Section 2.5 are aimed at achieving compliance with the current emission limits (1986 TA Luft).

This section discusses the techniques required to achieve compliance under the tighter emission limits of the Solvent Emissions Directive which is to be incorporated within the IPPC regime. This is a longer-term requirement and it is intended to implement these techniques in 2007.

The options for end of pipe abatement of residual VOC emissions are as follows:

i. Granular activated carbon adsorption plants

ii. Molecular sieve adsorption

iii. Absorption plant including selective oil/liquid scrubbing plant

iv. Thermal oxidation/incineration

v. Catalytic decomposition

vi. Compression/refrigeration/cryogenic systems

The suitability of these technologies is discussed in Section 3.2 based on the process duties for the BPC and Nitration plants (Section 3.1).

Process duty

In the conceptual design of the final abatement system it is important to understand that the chemical synthesis and separation steps involved in the manufacture of the New Chemical Entities, including Fesoterodine and Lacosamide are heavily reliant on the use of chlorinated solvents including Dichloromethane. It follows that the BPC emissions include streams that contain chlorinated organics (Dichloromethane). The opportunity to segregate these streams and treat separately to the non-chlorinated streams needs to be explored.

Appendix 1 includes the basis of design in terms of process duty. It also includes an assessment of the emissions from the flameless regenerative oxidiser.

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PHARMA

In terms of process duty, the two categories of emission can be summarised as follows:

BPC Plant Non-Chlorinated Streams:

Operating Maximum Minimum Flowrate Nm3/h 5000 10000 3000 Pressure mbarg atmospheric 10 -10 Temperature OC IO-15 30 5 voc mg/m3 1000 - 2000 8000 500

VOC Components Contaminants

Acetone IMS Methanol Toluene Ethyl Acetate MTBE Acetic Acid MEK IPA Hexanes Heptanes THF Butane lsobutylene

water: (saturation at up to 30°C) Dichloromethane: traces HCI: cl Omg/m3 NH,: c5 mg/m3 H2 cl 000 mg/m3 balance: air

BPC Plant Chlorinated Streams:

Operating Maximum Minimum Flowrate Nm3/h 50-100 400 5- 10 Pressure mbarg 5-l 0 50 atmospheric Temperature “C o-1 0 50 -10 voc mg/m3 20-50000 200000 0

Note: maximum conditions not coincident. DCM load will range from 5 to 40 kg/h.

VOC Components Contaminant

DCM Acetone IMS Ethyl Acetate Toluene Hexanes Heptanes

water: (saturation at 5’ - 1 O’C) HCI: cl0 mg/m3 (ex scrubber) balance: air

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PHARMA

The chlorinated streams are low flow with a highly variable concentration.

The options for dealing with the chlorinated streams are as follows:

1. Recover the Dichloromethane by a 2 stage absorption / desorption plant

2. Remove the Dichloromethane prior to combining the streams and treating in a common abatement plant

3. Combine the streams and treat in a common abatement plant designed to accommodate the chlorinated organic content

The capital cost of Option 1 has been investigated and it is estimated that such a plant would cost e640,OOO - c770,OOO. The value of the recovered Dichloromethane could not justify this capital cost.

Option 2 limits the flexibility of the overall system in that separate headers need to be maintained for segregation of the chlorinated streams. Scrubbing out the Dichloromethane as a pre-treatment step results in the production of a difficult waste effluent stream. There is also the potential for traces of Dichloromethane in the non-chlorinated streams. The more robust solution is therefore to allow the combination of the streams and treat in a common abatement plant. This is the approach used in the basis of design.

The process duty for the BPC abatement plant is therefore a combination of the chlorinated and non-chlorinated streams listed above.

The process duty for the Nitration plant is as follows:

Nitration Plant

Operating Maximum Minimum Flowrate Nm3/h 5000 5000 1500 Pressure mbarg -15 atmospheric -30 Temperature “C 0 40 -5 voc mg/m3 1000-2000 8000 500

VOC Components

Toluene MIBK IMS Acetic Acid

Contaminant

water: (saturated at IO” - 15%) balance: air

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3.2

3.2.1

Best Available Techniaue Options

Appendix 3 of this report gives an outline discussion of the main VOC abatement technologies that have been considered in this assessment.

However, the requirement to run the BPC, Nitration and future pharma plants as multi-purpose units, combined with the nature of the solvents used reduces the number of options for VOC abatement.

In addition, one of the main elements of the basis of design for these abatement techniques is the requirement to achieve the relatively low compliance limit of 20 mg/Nm3 for VOCs. Not all of the techniques in Appendix 3 can achieve this high degree of VOC removal/destruction.

Elimination of Techhiaues

Due to the multi-purpose nature of the site and the high degree of removal/destruction required, the technologies not taken forward for detailed consideration are:

. carbon adsorption,

. membrane technologies and

. absorption.

The principal disadvantage with using granulated carbon is that for multiple solvent streams the adsorption capacity of the bed can be affected. One solvent will adsorb at the expense of leaving another less selective solvent to pass through. A further disadvantage is that a significant amount of wastewater is produced following regeneration of the bed with steam. There are also safety concerns due to the highly reactive nature of the carbon that can produce high heats of combustion and the potential for bed fires, particularly during periods of start-up and shutdown.

Typical levels of VOC in exhaust gas for carbon adsorption plants are 20 to 80 mg/Nm3 (depending on organic). In terms of the carbon regeneration 4kg of steam (per kg of organic adsorbed) typically leaves sufficient VOC on the carbon to provide measurable levels of VOCs’ in the exhaust gas.

Due to the asymptotic nature of the relationship between steam used and residual VOC in the carbon, achieving VOC levels below the typical requires significantly more steam to the point that it is economically unviable.

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SCHWARZ PHARMA

3.2.2 Techniques for Detailed Consideration

Molecular sieves and similar membrane systems have similar advantages and disadvantages but water vapour and some solvent materials can also poison the adsorption media.

Absorption using selective solvents and polyethylene glycol can achieve a 98% reduction in releases but again there is a resulting liquid waste stream of glycol and solvent that needs to be desorbed, resulting in an aqueous /solvent mixture for disposal or effluent treatment. The glycol is also very expensive.

The remaining technologies that can comfortably achieve the low emission limit of 20 mg/Nm3 for a mixed VOC stream are:

.

.

.

cryogenic condensation catalytic thermal oxidation and conventional thermal oxidation (recuperative, regenerative or flameless)

Once the waste stream is characterised, a choice must be made between the recovery or destruction of the organic content of the emission. Recovery obviously becomes more viable if there is an immediate re-use option on site but off-site recovery or re-use can also be considered.

Environmentally, recovery followed by re-use, is generally preferable to any of the destruction techniques. However, there are a number of factors to consider:

. Complexity of the emission. It is harder to recover mixtures of VOCs compared to single compounds. Recovery is generally based on some physical property of the VOCs and in complex mixtures these properties may be very close to each other making separation more difficult.

. Potential re-use of recovered solvent. The quality requirements of many pharmaceutical processes are extremely strict. This extends to the purity of the solvent to be reused. If recovery options cannot economically achieve the required purity then the option becomes less attractive.

. Ultimately, the regulatory emission release limits must be met. Certain recovery technologies are limited by the treatment efficiency. With cryogenic condensation, very low residual concentrations can be achieved but at a high utility cost.

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SCHWARZ PHARMA

The Draft Reference Document on Best Available Techniques for the Manufacture of Organic Fine Chemicals refers to the generic technology of Thermal Oxidation. This includes a number of configurations such as

. regenerative l flameless (a variation of regenerative) . recuperative and . catalytic.

In some texts and discussions, catalytic oxidation is separated from the conventional high temperature oxidation technologies.

The thermal oxidation technologies are similar in operation but Catalytic oxidation offers the opportunity to oxidise at a lower temperature by using precious metal catalysts based on Platinum/Palladium. Depending on the solvent mixture the oxidation temperature can be as low as 250 X.

Some solvents are known to mask and poison the catalyst, particularly those containing chloride ions e.g. dichloromethane and hydrogen chloride vapour. There have been developments in catalyst bed design, which can accommodate the treatment of low concentrations of halogenated VOCs. However, the multi-purpose nature of the Schwarz site and the reliance on chlorinated solvents in the sites main processes make catalytic oxidation a risky option for abatement.

The option of catalytic oxidation over conventional thermal oxidation is attractive because of the lower temperature and fuel requirements. The site does not have a piped natural gas supply so minimisation of fuel input is an important consideration.

However, some of the regenerative thermal oxidisers operate at an extremely high thermal efficiency and can achieve equivalent auxiliary fuel requirements. Thermal oxidation has the advantage of the potential use as a liquid solvent disposal option.

Recuperative oxidation involves the recovery of energy produced by burning a support fuel to achieve VOC destruction; e.g. natural gas. A simple primary or secondary heat exchanger is used to heat the incoming process air using hot waste gases. The energy recovery efficiency however is limited to approximately 76% based on an oxidation temperature of around 760 degrees Celsius. Hence, this type of oxidiser requires very high VOC loads to avoid using significant fuel input to augment the energy available from the solvents.

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PHARMA

3.3

3.3.1

Regenerative units recover the energy used for VOC destruction within the oxidiser heat exchange media itself and can achieve energy recovery efficiencies of 95%. The regenerative designs can operate at low VOC concentrations and does not require a reliance on support fuel. This specific design can also use alternative fuel options including electrical heating.

The technologies recommended for consideration for the proposed process duties of the BPC and Nitration plants are therefore:

l Low temperature cooling/condensation with recovery of solvent and

l Regenerative thermal oxidation with heat recovery

The following features can be applied to both technologies, which makes them suitable potential candidates for both the BPC and Nitration plant applications:

. Both of these two options are capable of achieving very low final emission concentrations so there is a degree of future proofing included in the technology choice.

. Both technologies are non-specific in their treatment. Cryogenic condensation requires control of the exchanger temperature but it is capable of recovering most VOCs.

Best Available Technique Assessment

Appendix 2 is the detailed BAT assessment for the two options which has been assessed in terms of the short and long term emissions and other environmental factors such as global warming potential, waste generation etc. The conclusions of the BAT assessment are summarised in Section 4.

Sections 3.3.1 and 3.3.2 discuss the two abatement options of cryogenic condensation and regenerative thermal oxidation in more detail.

Cryogenic condensation

Cryogenic condensation can handle all VOCs and volatile inorganics, irrespective of individual vapour pressures. This non-selectivity makes it suitable for further consideration for the Schwarz site. The low temperatures possible with liquid nitrogen allow for very high removal efficiencies.

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5CHWARZ PHARMA

With the proposed system the liquid nitrogen is not vaporized in direct contact with the emissions stream, but the VOC emissions are condensed by liquid nitrogen to provide the cooling source. This indirectly cools the process stream down to the required temperatures. The vented nitrogen can then be returned to a header for use in inerting operations.

With low flow rate emissions it is possible that the demand of liquid nitrogen for refrigeration can be balanced with the total gaseous nitrogen demand, which offsets the operating cost of the system.

Recirculating cold nitrogen gas in the condenser cools the process flow stream. At the outlet of the condensers, the process stream reaches the control temperature, the condensed liquid solvent then drains to the bottom of each condenser. The cold vapor stream is vented after an economizer recovers the energy by exchanging it with the coolant recirculation flow, in order to improve the energy efficiency of the equipment and therefore minimize the use of liquid nitrogen.

Warmed process gas exits through the vent stack. The use of the gaseous nitrogen as the cold working fluid provides excellent temperature control. The system thus recovers virtually all of the cooling value available from the vaporizing liquid nitrogen. This also makes it possible to closely control the tube wall temperature in the condenser, which helps to avoid localized freezing.

Control of the liquid nitrogen input rate regulates the temperature of the coolant stream. The condenser design allows for frost buildup due to freezables in the emission stream. Dual condensers alternate automatically in a freeze/thaw cycle for continuous operation. The on-line condenser does not freeze all of the material that enters the unit. The design of the coolant circuit ensures that most material will condense and drain from the working exchanger.

Since the nitrogen system has no rotating components, the system is inherently more reliable than systems based on mechanical refrigeration. The system is also compact in size, and can be brought onto site as a skid-mounted module.

In summary, the advantages of this cryogenic condensation technology are:

. High VOC removal efficiency

. Scope for improved removal efficiencies (lower operating temperature)

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PHARMA

. Potential for reuse of recovered solvents

. Operating cost potentially offset by existing requirement for inerting Nitrogen

. Flexibility and response to changing feed conditions

There are potential operating problems related to freezing of water vapour in the gas stream that are addressed to some extent by the inclusion of dual condensers. However, it is preferable to eliminate as much water vapour as possible prior to the cryogenic unit.

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SCHWARZ PHARMA

As an example of the operating temperatures required for cryogenic condensation, the following solvents are removed at the given temperatures:

Solvent

Dichloromethane Toluene Methyl ethyl ketone Acetone Methanol

Operating temperature required, “C

-95 -65 -75 -86 -60

Note: These removals were at higher initial concentrations than would be expected from thr+ Schwarz Pharma application

The payback of the investment in this technology is enhanced if the condensed solvents are recoverable to the extent where they can be re-used.

This requires a downstream recovery process such as distillation. With a complex mixture of condensed solvents there is a potential for azeotropic combination that will make the recovery more difficult.

Ideally, when a mixture of two liquids is distilled the lower boiling material vaporizes first and is collected separately from the second material. However, sometimes the two materials form a constant boiling mixture and are collected together even though they have different boiling points. In solvent recycling, this can prevent the collection of a pure solvent.

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SCHWARZ PHARMA

Some common azeotropes are included in the tables below:

Common Azeotropes

Azeotrope Wt.% A

Component A Component B Boiling Point A

Boiling Azeotrope Point B Boiling

Point

Water 64.5 =C Non- Azeotrope

Water I

Ethanol 100 “c 78.3 “c 1 78.2 “c 1 4 %

Water lsopropanol 100 “c 82.3 “c 80.3 “c 12.6 %

Water Acetone 100 “c

Water

Water

Acetonitrile

Ethyl Acetate

100 “c

100 “c

Water Acetic Acid 1100% 1118°C INon- 1

40 “c 38.1 =C I 1.5%

Boiling I

Azeotrope Point B Boiling Point

Component A Component B Boiling Point A

Azeotrope Wt.% A

Dichloromethane Methanol I 40 “c 64.5 =C 1 37.8 “c

Dichloromethane Hexane 40 “c

Dichloromethane I Ethyl Ether I 40 “c

Dichloromethane Acetone 40 “c 56.2 =‘C Non- Azeotrope

Acetone Hexane 56.2 “c 68.8 “c 1 49.8 =C

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SCHWARZ PHARMA

An indicative capital cost for typical cryogenic systems is E500,OOO per 1000 Nm3/hr of VOC laden gas.

It is therefore critical to minimise the volumetric flowrate of the VOC emission at source, where practical. This in turn increases the concentration and improves the efficiency of the VOC control technology.

Utilities and Operatina Costs

Manufacturers’ quoted utilities usage are:

Nitrogen IO-15 kg/kW cooling Pressure drop 2-5 kPa Electrical Power 70 kW/i 000Nm3 Estimated manpower 1 staff day per week

Operating & Maintenance Aspects

The unit can effectively be fully automatic with the main labour input being associated with the operation of the scrubber unit. This will mean that the unit will function with minimal operator intervention and will be within present operator competence of the site.

Location

Location of the unit at ground level adjacent to the respective plant e.g BPC plant. This is close to the existing bulk nitrogen supply. This will require a transfer duct from the BPC building to carry the vent gas across. Application of this technique for the Nitration plant is more difficult because of the existing location of the bulk nitrogen supply.

Cryogenic condensation using liquid nitrogen as the condensation medium has a number of advantages for the Shannon site:

l Bulk nitrogen is already used on site

l Spent nitrogen from the condensation process can be used for inerting purposes

l In theory, very high efficiencies can be obtained, resulting in low emission concentrations

l There is some future proofing within the system to guard against changes in feed composition and/or stricter emission limits. The main operating variable is operating temperature

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3.3.2

SCHWARZ PHARMA

l It is a non-specific technology that will condense a range of organics and inorganics

The potential problems that will require consideration during design are:

. The relatively high Schwarz Pharma flowrate. This technology has a high capital cost so it is essential to minimise the volumetric flowrate by good header design and control of VOC concentration. The process duties listed in Section 3.1 are realistic calculations of what will be required.

. The potential for re-use of the recovered solvent and the practical limitations of distillation recovery

Regenerative Thermal Oxidation

Principles of the Reaenerative (Flameless) Oxidiser

Many of the organic pollutants that are discharged from processes, such as solvents, are in fact high quality fuels. An appropriate method for their destruction is therefore combustion. The problem with this method is however that the pollutants are usually diluted with air to such small concentrations that they cannot sustain combustion. Often the concentration is far below the flammability limit for a typical solvent that lies in the region of 30-40g/m3. A contamination of air with 0.5 g/m3 of a solvent, such as xylene, would mean that the air has energy content, in the form of heat of combustion, which would raise the temperature of the air approximately 15X at reaction. However, in order to obtain reaction a temperature of at least 800-900% is required.

The combustion reaction follows the same physical laws as any reaction and the rate of reaction is a function of temperature. The reaction rate increases with temperature and there is a point at which the rate of reaction increases very rapidly. This is often termed the “combustion temperature”. This reaction temperature differs very little between different hydrocarbons and is found to be, depending on the definition used, somewhere in the interval 850-950QC.

The conventional way of burning hydrocarbons under these conditions would therefore require additional heating by extra fuel in the form of gas or oil. For the reaction process to proceed, so much extra fuel is needed that it becomes very

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SCHWARZ PI-IARMA

costly. In order to decrease the fuel consumption it is possible to preheat the inlet combustion air through heat exchange with the hot outlet air. By using conventional recuperative heat exchanger technology half of the heat in the air outlet can be recovered in this way thus halving the fuel requirement. However it is not economical to obtain greater heat recovery with this method as the capital costs for the heat exchanger will more than balance the saving in fuel costs.

The flameless oxidizer is a method of achieving the reaction temperature where the heat exchange efficiency is such that the need for additional energy can be greatly reduced or even totally eliminated. The flameless oxidizer is therefore a high temperature system where a regenerative heat exchanger is integrated with the combustion equipment.

The VOC destruction efficiency of the flameless oxidizer as a measurement made from process inlet gas concentration to outlet concentration, averaged over a single valve cycle for a standard system is guaranteed to be not less than 98%, with optional configurations to achieve destructions of 99.5%+.

The combustion efficiency of the flameless oxidizer system is much higher than 98% as described later in this section. The main reason for the difference between destruction efficiency and combustion efficiency is due to leakage through the valves and release during the change of flow direction through the bed. During the change in flow direction, there will be an instantaneous emission of untreated process air from the oxidizer. This is due to the change in flow direction of the air which was being delivered to the flameless oxidizer. This air will, at the time of valve change, become outlet air. In practice, the magnitude of the spike is very small and equates to significantly less than 1% of the total emission. The duration and concentration of the spike are very difficult to measure but typically, the concentration of the spike is less than 50% of the inlet concentration and lasts for less than 1 second. In this case, the second oxidizer valve operation will be controlled to avoid co-incident operation with the first oxidizer valve and hence the peak will be destroyed by the second oxidizer.

Combustion efficiency is a measure of the true destruction across the bed not including leakage through valves and release during the flow direction change through the bed. The combustion efficiency of the flameless oxidizer will be greater than 99.9%.

All combustion takes place within the ceramic matrix and is accomplished under three conditions:

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S;C’H WAR2 PHARMA

1) Large excess of oxygen 2) Thoroughly premixed fuel-air mixture 3) Reaction within a low and narrow temperature range.

Even at reaction the temperature of the gas is always close to the local ceramic temperature.

Together these conditions guarantee: n Complete combustion 9 Virtually no production of thermal-NOx

(co,1 ppm) from nitrogen in the air.

When using conventional equipment for continuous combustion, the chemical combustion reactions can be driven to near completion and the ‘combustion efficiency’ can be better than 99.9%, particularly when the reactants (fuel and air) are thoroughly mixed before combustion. In a burner, the mixing of fuel and air usually takes place in the burner at the same time as the combustion reaction.

Compared to combustion, mixing is a slow process and can be seldom complete in a flame. Thus in a flame there will be some flow paths that are starved of the oxygen and other starved of fuel.

The result is incomplete combustion and hence a reaction efficiency which deviates from 100%. This will manifest itself in the formation of soot, carbon monoxide and a wide range of other products of incomplete combustion (such as dioxins).

In the flameless oxidizer the combustion reaction takes place within a heat exchange and heat storage matrix of ceramic material. The flow channels within the bed are of such small average diameter and have such good heat transfer characteristics that the gas temperature is always kept within 50°C of the local ceramic temperature. Hence the combustion reaction takes place under strict temperature control with no short-cut paths at lower than average temperature - there is no risk of quenching. The air and combustible vapours are intimately mixed long before they enter the combustion bed and the reaction proceeds with a large excess of oxygen (more than ten times the theoretical oxygen requirement is present within a very short range of each fuel molecule). This ensures very high combustion efficiency in the bed.

The gas mixture is forced through narrow channels with hot walls which completely control the gas temperature to an upper value. As no combustion can take place until the temperature of the reactants is high enough, there is no risk of any significant reaction until the gas mixture reaches the design position in the bed where reaction will proceed very rapidly. The conditions for the reaction are so good that the

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P H ,A R M A

reaction is completed after a path of approximately 10mm through the bed matrix. Therefore, the actual reaction zone occupies only a small portion of the bed. A high temperature plateau much wider than the reaction ‘window’ occupies the centre of the bed (and is usually approximately 1 meter wide - over 60% of the bed material). The remainder of the bed is provided for heat exchange and the cooling of the waste gases through the critical temperature window for de novo dioxin is much faster with the flameless oxidizer than a conventional combustion system.

Process Description

It should be noted that the Nitration plant does not currently use chlorinated solvents. Therefore, under the current process duties, the following items would not be required for the Nitration plant system:

0 Venturi Scrubber 0 Packed Tower Scrubber 0 Cooling Tower

The full system would be required for the BPC plant and would include the following:

/n/et LEL Control Inlet LEL monitoring to the oxidizer ensure that an explosive mixture is not permitted to enter the RTO. If a high level is reached then the oxidizer is bypassed and the process fume is vented to the stack.

Inlet Dilution Air Fan Sys tern The system will comprise of a dilution air fan with AC drive and controls, this will be used in conjunction with the measured inlet LEL to provide a controlled volume and inlet concentration to the oxidizers. Dilution air will be safely introduced to the process emissions through a Control Valve, the amount of dilution air being balanced to optimize the VOC concentration based upon LEL measurements. The flameless oxidizer will operate autothermally at VOC concentrations of around 2g/Nm3 and has a maximum design allowance of 25% LEL, hence the system will be controlled to dilute emissions to achieve optimum inlet conditions.

LEL instruments provide a further level of safety for operation of the oxidizer. Under conditions of high LEL, or oxidizer failure, the flow can be diverted directly to atmosphere.

Thermal Oxidizer

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PHARMA

The VOC fume enters the single bed flameless regenerative thermal oxidizer. Natural gas or electrical heating can be used as an auxiliary fuel when process emissions fall below the autothermal point of the system.

Heat Exchanger After the oxidizer the hot gases enter a heat exchanger which heats the cooler stack gases to help minimize plume formation. The gases at this time will contain HCI, so the heat exchanger will be manufactured from high nickel content metal. The gas temperature will drop during this heat exchange process.

Venturi Scrubber (not required for Nitration plant) Chlorinated compounds will form hydrogen chloride during the oxidation stage, which will require further treatment. After the heat exchanger the gas is further cooled in a venturi scrubber. The caustic water will remove HCI, but its primary function is to ensure the gasses are cooled before they enter the packed column. The deletion of this item and the insertion of a packed tower section may be possible dependant on the inlet VOC loadings and process flow conditions, which will determine the exit temperatures that will be seen from the thermal oxidizer exit.

Packed Tower Scrubber (not required for Nitration plant) The gas enters the packed tower scrubber to remove the HCI.

Heat Exchanger The gas then re-enters the heat exchanger for re-heating and exits the system via the exhaust stack.

Cooling Tower (not required for Nitration plant) A cooling tower provides cool water for the venturi and the scrubber.

NOx Removal The RTO proposed is a flameless system with zero thermal NOx generation. The exit NOx condition will be a function of the maximum inlet condition for the nitrogenated solvent present. Estimates show that maximum inlet conditions will vary between 5-7 kg/hr dependant on the proportion of Acetonitrile and DiMethyl Formamide present in the feed stream. This item requires further discussion.

Dioxin Removal Additional dioxin removal equipment is not perceived as being necessary. The system proposed has a rapid quench design.

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PHJJMA

Section 4.2.6 of the Reference Document on Best Available Techniques for the Manufacture of Organic Fine Chemicals discusses the recovery of HCI from flue gases by absorption in a scrubbing column. This particular application is intended for the downstream treatment of exhaust gases from thermal oxidation in chlorination processes. It is unlikely that for the process duties considered the recovery of HCI would be justifiable. The proposed configuration allows for the removal of HCI upstream of the thermal oxidiser oxidiser.

A further variation on this technology that needs to be considered is the use of the oxidiser as a liquid solvent treatment plant to provide further energy recovery. This option requires consultation with the environmental regulators.

costs

Preliminary quotations from suppliers for this particular application indicate that the equipment cost for the BPC system would be approximately GIOO,OOO. The Nitration plant system does not require the post treatment for HCI and the cost would reduce to e690,OOO.

Natural gas is currently not available to the site but alternative auxiliary fuel systems can be used including fuel oil or electrical power. This flameless unit can be configured for electrical auxiliary operation.

Operatina & Maintenance Aspects

The unit can effectively be fully automatic with the main labour input being associated with the operation of the downstream scrubber unit. This will mean that the unit will function with minimal operator intervention and will be within present operator skills areas.

Location

Location of the unit at ground level on the existing site of the tank farm. This will require a transfer duct from the BPC building to carry the vent gas across.

The following points are also applicable:

l The flameless regenerative oxidiser will meet all projected emission requirements

l The technology is a destructive technique which must be justified against the potential recovery

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SCHWARZ PHARMA

option of cryogenic condensation. Section 4.2.9 of the Reference Document on Best Available Techniques for the Manufacture of Organic Fine Chemicals discusses the feasibility of VOC abatement options. One of the conclusions from a study of seven case studies is that recovery techniques for VOCs are almost never cost competitive with destruction techniques, unless the recovered material has greater value than its fuel value.

. There is a high energy cost for low concentration gas streams

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SECTION 4

SCHWARZ PHARMA

BAT CONCLUSIONS

There are a number of measures planned for implementation in 2005 which are aimed at reducing the site emissions to air.

These are all part of the overall upgrade to the site and the BPC plant in particular. A number of improvements to the Nitration plant are being implemented during 2005 in order to bring the site into overall discharge compliance.

The short term (2005) measures discussed in Section 2 include the following:

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Development of Environmental Management Systems

Upgrade of primary condensers

Improvement to monitoring

Automation of utility services

Upgrade of vacuum systems

Optimisation of BPC layout

General Utility upgrade

Primary emission abatement (vent headers and scrubbing)

Installation of new and complete LEV system

Installation of new HVAC system

Removal of existing control panels and installation of modern, improved control panels

Automation of vessel jackets (Heat/Cool) and Utility Services (vessel overheads) so as to allow “common building services”

Containment and chemical handling upgrade including improvement to vessel charging operations

The longer-term objective is to further reduce VOC emissions to allow compliance with the Solvent Emissions Directive which is incorporated in the IPPC regime. In this context end of pipe abatement technologies required for the BPC and Nitration plants. These have been assessed in Section 3.

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SC’HWARZ PHARMA

The two candidate options of cryogenic condensation and regenerative (flameless) oxidation have very similar environmental releases in that they are both capable of, and would be designed for, achieving the requirements of the Solvent Emissions Directive (a VOC emission concentration of c20 mgC/Nm3).

There is no difference between the Environmental Quotient of either option for the long and short-term releases of VOCs.

There are some minor differences between the options in terms of the secondary impacts such as:

m Global warming potential

n Ozone creation potential

n Releases to water

. Plume visibility

However, the main difference relates to the volume of solvent that would be recovered by the cryogenic condensation process. For the Schwarz Pharma application, this solvent is a complex mixture with potential azeotropes. There is limited scope for solvent reuse in pharmaceutical processes and the potential for contamination (loss of entire batch and risk to patient health) outweighs potential benefits.

In addition to the above points, there is a novelty factor associated with cryogenic condensation. Although the theory is sound, there are very few cryogenic units operating on multi- solvent streams at this sort of scale. There is therefore an associated technical, environmental and financial risk in this particular application. There is an apparent large variation in quoted capital costs for such systems due to the lack of background information and historical installations.

The technology of choice for the Pharmaceutical industry for VOC abatement on multi-product facilities over the last 10 years has been thermal oxidation in its various forms and configurations. This is reiterated in Section 4.2.9 of the Reference Document on Best Available Techniques for the Manufacture of Organic Fine Chemicals that considered seven case studies of various VOC loads and flowrates.

Through the Solvent Emissions Directive, Climate Change Levy and carbon tax thresholds being imposed, techniques that can recover solvent and/or energy may require closer scrutiny to assess potential payback. For the calculated process duties the costs for cryogenic condensation of the total VOC load appear to be excessive and prohibitive.

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The capital cost of the flameless oxidation option is significantly lower than that of the cryogenic condensation unit. The flameless oxidiser is currently deemed to be the Best Available Technique for the treatment of residual VOC emissions from the BPC and Nitration plants. In summary this is because:

l There is no difference in the final release concentrations achievable with either option

l Both options will achieve a very high degree of VOC removal in line with the requirements of the Solvents Emissions Directive

l The recovery of a mixed stream of condensed solvents causes additional practical problems for the site which cannot easily be addressed (location of additional storage, increased fugitive emissions)

l Technical risk due to novelty of cryogenic condensation at this scale of flowrate

l Technical risk due to novelty of cryogenic condensation for this complex mixture of solvents

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PHARMA

SECTION 5

5.1

5.2

SAFETY, HEALTH & ENVIRONMENTAL

The environmental requirements and VOC emission limits are the focus of the choice of technology in Section 3. Additional aspects are addressed in this Section.

Crvoqenic Condensation

The target VOC emission limits can be achieved comfortably with this technology. 99% recovery is possible. The emissions from the process will be vented to atmosphere through a stack which may be placed near the existing boiler house stacks. Air dispersion modelling of the VOC dispersion will be carried out to compare the present dispersion pattern and levels with the estimated future values.

There is a positive environmental impact if the condensed solvent is recovered and re-used. The reuse on site may not be possible because of process purity considerations. In this case, the recovered solvent may be sold externally for a lower grade end use requirement.

Reaenerative (Flameless) Oxidation

NOx, SOx and HCI levels are expected to be below 5 mg/Nm3 due to the low generation rate of NOx (typically 2ppm) and the alkaline scrubbing system. The target VOC emission limits can be achieved comfortably with this technology. 99% recovery is possible. The emissions from the process will be vented to atmosphere through a stack which may be placed near the existing boiler house stacks.

Dioxin and furan production are not expected to occur as the conditions for the De Novo Synthesis reaction are not present and these materials are not present in the feed gas.

The water from the scrubber will contain a small amount of alkali and approximately 12 kg/hr of salt formed by the neutralisation of hydrogen chloride by caustic soda.

Salt has an inhibitory effect upon biological systems at high concentrations however the mass of salt entering the effluent treatment plant is small in comparison with the total site discharge and its effect is minimal.

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SCWWARZ PHARMA

The main safety issue associated with the plant is the risk of fire from two sources:

. Ignition of flammable gas mixes on hot external surfaces, which can be minimised by placing the unit outside of the possible risk zones

. Flash back from the unit along the transfer duct

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SECTION 6 PROGRAMME

For the long-term options it is estimated that the front-end design of a VOC abatement plant will take approximately 12 weeks. It is proposed to carry out a value engineering exercise to assess variations of the main technology options using weighted factors for each key Schwarz Pharma criteria. It is further proposed to present the design options for review with the Environmental Protection Agency.

It is proposed to then produce the basic engineering design and specifications for the VOC abatement plant.

The current modifications to the BPC and Nitration plants are ongoing and these are aimed at bringing the facilities under compliance with the existing licence. The long-term VOC abatement plants for both the Nitration and BPC plants will be procured in 2006 for installation in 2007. The initial indication of lead-time for the regenerative thermal oxidiser is of the order of 24-32 weeks.

The following project programme can be envisaged:

Preliminary design, specification and tender issue (Q4 2005) Return of bids, Bid Analysis (Ql 2006) Order Placement (Q2 2006) Detailed Design (Q2 - Q4 2006) Construction and Delivery of unit to site (Q4 2006) Installation of unit and Ducting (Ql 2007) Commissioning and validation (Q2 2007) Full operation from Q2 2007

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