Managing Emissions from Pharmaceutical Reactions

Jose P. Arencibia, Jr., Arencibia Associates Inc.
Charles F. Kramer, Zerem Inc.

Contents

Abstract
Introduction
Operating Considerations of Conventional Technologies
Alternative VOC Emissions System
Comparisons
Conclusions
References

Abstract (Back to Top)
Most large pharmaceutical manufacturing plants consist of multiple small reactors or unit operations supported by centralized utilities, including plant blanket nitrogen, a vacuum header, and a gaseous vent header. The combination of these utilities constitutes the "highway" through which most of the plant emissions are carried to the environment. Gas streams carrying toxic emissions are diluted to lower threshold limit values, lower explosion limits, or to meet other emission requirements. More recently, emissions are being combusted in a thermal oxidizer, either directly or in combination with dilution or other emission reduction steps. These methods of emission "reduction" are not only ineffective in reducing volatile organic compounds (VOC), but actually produce other toxic compounds including HCL and dioxins; toxic emissions such as CO, NOx, Sox, and ozone; as well as CO₂ and CF₄, which are greenhouse gases. They do not address the fundamental source of the problem: the vapor/liquid equilibrium properties of the reactants in individual reactors.

Alternative methods that reduce or eliminate emissions at the source by condensing or trapping all volatile reagents and pollutants, returning to the reactor those which can be reused in the reaction, have significant advantages over conventional thermal oxidizer based systems. "Point of source" emission management systems may be integrated with specialized reactor designs to contain and isolate volatile emissions and/or return them to the reactor. Existing reactor systems may be retrofitted to achieve additional heat transfer and "point of source" emission control. For sites with multiple reactors or existing unit operations, "point of collection" systems may be configured to include a network of gas streams from multiple reactors, with the capability of selecting contaminants, concentrating them, and rendering them innocuous. Economic analysis of typical applications of "point of source" and "point of collection" emission management systems shows significant reduction in cost of inert gases, electrical power, combustion fuel, capital, and operating costs—as well as flexibility to use alternative, more-desirable carrier gases such as argon or helium.

Introduction (Back to Top)
Consider a generic 1000-gallon reactor that uses methanol as a working solvent and gaseous nitrogen (GAN) as the inert "blanketing" medium. Table 1 depicts the vapor pressure and concentration of methanol in the vapor phase at 0.34 barg total pressure in the reactor, assuming ideal gas phase and no interaction between the methanol and the GAN [1].

Assume the reactor operator is required to keep a GAN purge of 5 Nm³/hr on the vapor space of the reactor. Column 4 and column 5 in Table 1 depict the rates of methanol transported from the reactor in equilibrium with GAN. Note that a higher purge volume would only serve to emit more of this particular VOC to downstream emissions-handling systems.

Column 6 in Table 1 depicts the percentage of methanol in the carrier GAN stream emanating from the reactor. Safety considerations would require that these readings be reduced to below 1.5 % (well below the Lower Explosive Limit (LEL) of hexane in air [2]) to avoid having flammable mixtures in the exhaust header. Therefore, GAN would be added downstream of the reactor purge vent to bring this reading to a prudent 1.0 % methanol concentration. Columns 7 and 8 in Table 1 show the quantity of GAN that needs to be added in the exhaust header. Column 9 in Table 1 depicts GAN costs per hour assuming unit costs of $0.10/Nm³.

It is helpful to define a new term, exhaust ration (ER), as the total GAN required for purge and dilution to concentrations below an LEL of 1.0%, divided by the total VOC mass rate.

ER=TOTAL GAN [Nm³/hr]/VOC rate [Kg/hr]

Note that other consistent units may be used. ER can be viewed as a parameter that characterizes the required dilution for VOC, in order to stay below acceptable flammability levels.

For the reactor used in this example the ER for various operating conditions is depicted in Table 2.

In this example, process the VOC are en route to be emitted to the environment.

Operating Considerations of Conventional Technologies (Back to Top)
It is likely that the reactor used in this example may be located in a facility that has many other reactors and other unit operations with VOC emissions. Consider a facility with the following throughput that is piped to a thermal oxidizer or catalytic oxidizer [3]:

1. Up to 165 lb/hr (78.84 Kg/hr) of VOC including methanol, ethanol, acetone, isopropyl alcohol, methylene chloride, and chloroform.
2. Up to 3500 SCFM (5455 Nm³/hr.) total exhaust stream.

Note that the ER is approximately equal to 68.9 for this facility, when subtracting the volumetric flow contribution of 78.84 Kg/hr of combined VOC. If all these combined VOC are treated as methanol, the equivalent vapor phase flow is 22.23 Nm³/hr.

The corresponding cost of purge and dilution GAN for the facility described in reference 3 is $592/hr if the systems operate at an average temperature of 20°C and an average GAN purge rate of 5 Nm³/hr. per unit operation. The total GAN cost per year for a conventional VOC mitigation system is therefore $947,200 based on the same 1600 hr/year of operation and a GAN unit cost of $0.10/ Nm³.

Other variable operating costs for a conventional VOC mitigation system (excluding the cost of operating and maintenance personnel) include auxiliary fuel, power, treatment chemicals, replacement catalytic media, and disposal of secondary toxic wastes.

Alternative VOC Emissions System (Back to Top)
An alternative solution is to contain VOC emissions at the source.

Figure 1 represents a particular module of the point-of-source Zero Emissions (Zerem) VOC abatement system (patent pending). This module is located at each reactor and is designated as the VLSE (Vapor-Liquid-Solid Equilibrium) module:

• HXR-1 is a specialized heat exchanger with high-alloy wetted parts, which is a VOC condenser/dephlegmator and operates at temperatures down to –90°C, depending on the fluids used in the reactor. The refrigerant fluid(s) in HXR-1 is (are) N₂ and/or argon. The successful operation of HXR-1 depends on a sophisticated control algorithm to avoid freezing of VOC on the wetted surfaces. The HXR-1 controlled temperature is adjustable between –20°C and –90°C. HXR-1 condenses and returns a portion of VOC back to the reactor.
• HXR-2A and HXR-2B are "regenerators" with independent process and cooling/heating passages. Like HXR-1, HXR-2A, and HXR-2B are constructed of high-alloy wetted parts.
• HXR-2A and HXR-2B operate alternatively at temperatures down to –210°C and up to +20°C in alternating cycles. While at low temperatures, the process-wetted parts of HXR-2A/HXR-2B will freeze VOC components on the wetted surfaces. At high temperatures, HXR-2A/HXR-2B the VOC components previously frozen on the wetted surfaces will be melted and returned to the reactor.
• The geometry of HXR-2A and HXR-2B internal passages is critical to the successful operation of these units so as to minimize the equilibrium VOC mole fraction at the exhaust.

Figure 2 depicts the vapor pressure vs. temperature curve for methanol, featuring both calculated and empirical data [4].

Table 3 depicts the methanol concentrations at one exhaust condition for HXR-1 (-70°C) and two possible exhaust temperatures for HXR-2A/HXR-2B (-150°C and –200°C). Click here to see Table 3.) Note that the temperatures depicted in Table 3 do not represent the exhaust temperatures for purge GAN exiting the Zerem system, as several recuperative thermal exchanges bring the system exhaust temperature within 5°C of prevailing ambient temperature.

A preferred and cost-effective application for the Zerem VOC abatement system, includes a minimum of five (5) chambers that contain VOC at each reactor or unit operation to which they are attached. Each of these chambers operates independently and decoupled from each other. Referring to Figure 3, the Zerem VOC abatement system consists of the following modules:

MIXR Module
The MIXR module is a central thermofluid module that produces a utility fluid that is circulated throughout the system and provides the energy required to achieve desired refrigeration levels at individual VLSE modules. The MIXR module is connected to individual VLSE modules using specialized conduits. The MIXR fluid is inert, non-flammable, non-toxic, not a green-house gas, and has a high absolute thermal potential.

The MIXR module is typically located outdoors and requires a minimum 5m x 5m footprint and as much as 20m of height. It is significant that the MIXR module is not affected by the aggregate need for "turn-down," as it is operationally independent from the VLSE and Casinada modules discussed below.

VLSE Modules
VLSE modules are a plurality of individual and independent VLSE modules located adjacent to each reactor or unit operation and powered by MIXR. Each VLSE module captures and returns VOC evolved from its corresponding reactor or unit operation and refluxes to the source reactor. MIXR fluid is recycled and reconstituted/re-energized.

Casinada Modules (Optional)
The system can also be configured with any number of individual modules designed to work alongside each VLSE module and capable of achieving vacuum levels as low as 6 mTorr. These vacuum units feature no moving parts and are specifically designed to replace process vacuum pumps.

The Zerem VOC abatement system can easily be retrofitted to existing reactors/unit operations, requiring mostly vertical overhead space for each VLSE module.

Non-condensable byproducts, such as hydrogen are vented through a special catalytic (non-incendiary) flare that converts it (passively) to water vapor.

Comparisons (Back to Top)
The Zerem VOC abatement system is a highly cost-effective alternative to conventional strategies in use for controlling VOC emissions in the manufacturing of pharmaceuticals. Table 3 depicts quantitative comparisons; Table 4 depicts qualitative comparisons with three conventional systems.

Conclusions (Back to Top)
For operating costs of $32.00/hr and 60%–70% of normalized capital costs, 99.9999% of all VOC emissions can be eliminated using the ZEREM system. Or, for operating costs of over $600.00/hr and a minimum of 85% of normalized capital costs, the pharmaceutical industry can continue to degrade the atmospheric quality at substantially higher rates using conventional alchemy.

References (Back to Top)

1. Foust, Wenzel, Clump, Maus, and Anderson, "Principles of Unit Operations," John Wiley & Sons, Inc., New York, 1960.
2. Lewis and von Elbe, "Combustion, Flame and Combustion of Gases," Academic Press.
3. Parvesse, "Controlling Volatile Organic Compound Emissions in Pharmaceutical Manufacturing: Cost vs. Performance Options for Alternative Solutions," Pharmaceutical Engineering, November/December 1998.
4. Martin, "Thermodynamic and Transport Properties of Gases, Liquids and Solids," ASME, New York.

For more information: Charles Kramer, President, Zerem Inc., PO Box 987, Valley Forge, PA 19482. Tel: 610-933-8970. Fax: 610-933-3016. Email: ckramer@fast.net