Introduction U t R V s Q Energy is recovered by pre-heating incoming cold medium from 15°C (worst case) to 120°C with outgoing sterilized medium that is cooled from its sterilization temperature of 150 to 45°C prior to entering the process cooler where it is cooled further to 35°C. Medium is recycled back to a circulation tank (also called a surge or recycle tank) or diverted to the sewer during start up or process upsets (such as a decrease in sterilization temperature or an increase in system flowrate). This circulation tank can be pressurized or non-pressurized with the non-pressurized design approach requiring a second “flash” cooler before returning flow to the recycle tank to avoid flashing. Heating is accomplished indirectly using steam or hot water via a heat exchanger (HEX) or directly by mixing steam with incoming medium (steam injection). Cooling HEXs can use cooling tower/chilled water, but also may use vacuum to reduce temperature and draw off any accumulated water from direct steam injection. Continuous sterilization systems typically are pre-sterilized with steam by direct injection and/or with hot water. After attaining steady state with water flow, non-sterile medium feed is introduced. Various media components are sterilized in aliquots and sent to the receiving fermentation vessel with water flushed between them. A next generation, pilot-scale continuous sterilization system was designed, installed, started up, and validated. Demolition as well as retrofit was accomplished within an actively operating industrial pilot plant. Despite prior experience with a stick-built, internally designed system, a skid-mounted vendor design was selected consisting of five skids (recovery and heating exchangers, hot water loop and exchanger, retention loop, process and “flash” cooling HEXs, and switching valve station). Sterilized medium, obtained from the system at 40–100 lpm, typically was aliquoted into 800–19,000 L scale fermenters with lower flowrates being most appropriate for lower fermenter volumes. The design accommodated a range of different media types, including low solids levels below 5 wt.% and concentrated nutrient solutions. 10 35 Background Advantages 3 7 10 30 60 84 7 54 83 34 96 1 15 67 F o R o 1 52 12 54 l 88 15 96 96 96 97 36 38 Disadvantages of continuous sterilization primarily are that process control performance is critical since it is necessary to immediately divert flow of any inadequately sterilized medium, halt any further medium sterilization, and resterilize the system. In contrast, for a batch sterilization system upset, often additional hold time can be readily added to the sterilization. Continuous sterilizer systems also use dedicated equipment that usually is not well suited for other purposes. Applications Several relevant background papers on applications of continuous heat treatment of liquids have been published in the food, biowaste, and fermentation fields. 65 32 16 43 67 t T t K T o t o 1 1 \documentclass[12pt]{minimal}
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$$1/(f)^{{1/2}} = - 2.0\log _{{10}} [12\varepsilon /(3.7D) + 2.51/(N_{{\operatorname{Re} }} (f)^{{1/2}} )].$$\end{document} L D N Re 55 Influence of solid content of media 31 20 2 59 N Nu hD p K D p K 2 22 49 20 89 3 30 49 73 2 76 8 9 Experimental methods to quantify axial dispersion 74 81 50 46 1 76 44 Overview of operation 1 1 2 37 42 Table 1 Comparison of major changes in large continuous sterilization system Item Prior design New design Expected benefit/Risk or potential drawback Final heating method to attain sterilization temperature Direct steam injection Indirect heating loop Less dilution, improved stability with respect to source steam fluctuations, no adulteration from plant steam additives/higher cost Flowmeter Magnetic Coriolis Ability to sense deionized water/position of flag critical Number of different retention loop lengths t R t R Fewer fittings/limited visual inspection Flowrate turn down 60–100 lpm 40–100 lpm Avoids separate smaller unit/multiple ranges for tuning control Pressure safety device Safety valve only Rupture disc and safety valve with tell-tale pressure gauge Sanitary disc in process contact, evident when disc blown/added cost and maintenance Second cooler of same size as process cooler (“flash” cooler) Absent Present Ability to conduct water sterilization, installed marker for process cooler/extra expense Booster pump with pressure control on recuperator outlet Absent Present (used with centrifugal feed pump only) Sterile media at higher pressure than non-sterile media/increased complexity of tuning and operation Retention loop insulation Insulated box without packing, 4–6°C temperature drop Insulated box with packing, <2°C temperature drop More adiabatic and isothermal/modest additional expense HEX plate thickness 1/4″ 3/16″ Lower cost and higher surface area per unit volume/higher risk of breach HEX aspect ratio   Higher velocities/increased effect of channeling due to gap and drain notches Recuperator 2.7 3.46 Coolers 4.76 2.91 Heater 0.93 (horizontal cross flow for condensing service) 1.31 HEX process side channel thickness 0.25″ (coolers 0.375″) 0.25″ (coolers 0.25″) Higher surface area per unit volume/higher pressure drop HEX utility side channel thickness (coolers) 0.75″ 0.5″ Higher surface area per unit volume/higher pressure drop Aspect ratio is the HEX diameter divided by its width Fig. 1 a b  Table 2 System specifications and design criteria Parameters Design range (min–max) T 135–150°C V s 540–900 L Q 40–100 lpm at 15–60°C (water) 40–100 lpm at 60°C (55 wt.% cerelose) 40–65 lpm at 25°C (55 wt.% cerelose) 40–91.5 lpm at 25–60°C (50 vol.% glycerol) 40–88 lpm at 15°C (50 vol.% glycerol) Flow rates <40 lpm may not achieve sufficient back-pressure for the selected sterilization temperature to avoid flashing T in,cold,ext 15–60°C (water, 50 vol.% glycerol) 25–60°C (55 wt.% cerelose) Feed temperature of 15°C for 55 wt.% cerelose insufficient to maintain a solution t R 5.4–22.5 min P f 2 f 2 Sufficient pressures used to avoid flashing f 2 f 2 T 2.0°C for 40 lpm, 1.5°C for 60 lpm, 1.0°C for 80 lpm, and 1.0°C for 100 lpm Heat recovery (HR) >70–80% depending inlet feed temperature, media type and flowrate  78.9% (100 lpm water, 60°C)  75.5% (100 lpm 55 wt.% cerelose, 60°C)  78.9% (91.5 lpm 50 vol.% glycerol, 60°C) 2 93 Fig. 2 Overview of sterilizer phases  f 2 1 F o During water sterilization, incoming cold water was circulated for two passes (one pass if system was already hot from steam sterilization) at 60 lpm using the centrifugal inlet feed pump, after it rose to the sterilization inlet hold temperature of 150°C. It required previously steamed-through system block/drain valves since users were not comfortable that conduction adequately sterilized through them when closed. The non-sterile side of the recuperator HEX was bypassed to ensure that the sterile side reached sterilization temperature. Cooling water was applied to the “flash” cooler to ensure that the process cooler attained sterilization temperature. For the target sterilization temperature of just below 150°C and a 60 lpm water flowrate, the temperature reached about 148.5°C at the sterile side of the recuperator and 146.5°C for the sterile side of the process cooler. Water sterilization was redone during medium sterilization if medium diversion was necessary owing to system sterility upset. After taking immediate action to divert media away from the production vessel, water re-sterilization was conducted by (1) diverting flow through the “flash” cooler and enabling its pressure control loop, (2) fully opening the process cooler back-pressure valve, (3) conducting water re-sterilization, (4) enabling the process cooler pressure control loop, (5) fully opening the “flash” cooler back-pressure valve, and then (6) resuming medium sterilization. When switching from the “flash” to the process cooler, it was necessary to maintain sterile conditions. After the system was sterilized and running on water, typically in recirculation mode or emptying into the system sewer, the switching valve station was used to divert flow to distribution. Water now flowed to a waste vessel or the process sewer located near the eventual medium receiving vessel. After conditions stabilized, sterilizer inlet feed was switched from water to medium. Again, after conditions stabilized, flow was switched to the receiving vessel. When the receiving vessel was filled sufficiently, sterilizer effluent was switched back to the waste tank, sterilizer inlet feed was switched back to water, and then effluent switched back to either the recirculation vessel or system sewer. After media sterilization, a thorough water rinse was conducted at sterilization temperature and the system was cooled to 60°C for cleaning. Alkaline and/or acid cleaning solutions were used depending on the nature of the soil. After cleaning, the system was cooled and drained completely. Equipment design The system’s five skids were designed and fabricated at the vendor’s shop and delivered with only field installation of interconnecting piping required. To minimize design miscommunications, three-dimensional piping models were used for skid piping plans, which were able to be reviewed remotely by the customer. Ball valves were used instead of diaphragm valves for hot temperature service. Hazardous energy control was carefully considered with locking devices installed and valve placement selected for facile equipment isolation and operability. Equipment was citric acid-passivated after installation. Each relief device on the process side consisted of a flanged rupture disc (RD) with a pressure indicator and telltale as well as a pressure safety valve (PSV) that reseated after the source of excessive pressure was removed. These devices were placed directly after the positive displacement Moyno (Robbins and Myers; West Chester, PA, USA) system inlet feed pump, recuperator outlet, and booster pump. Discharges were piped to return to the feed tank for safety as well as for medium recovery. Piping was designed such that no PSV devices were required on the process side to minimize risk of system integrity disruption. Sample points were located on the inlet feed (pre-sterilization, prior to recuperator) and sterilized medium outlet (post-sterilization, after process cooler) lines. Heat exchangers 48 71 104 13 103 13 19 103 71 25 100 12 12 \documentclass[12pt]{minimal}
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$$ \begin{aligned}{} {\text{NTU}} & {\text{ = UA}}_{{{\text{HEX}}}} {\text{/}}Q_{{\text{M}}} C_{p} , \\ & {\text{ = (}}T_{{{\text{out,cold,ctr}}}} - T_{{{\text{in,cold,ext}}}} {\text{)/}}\Delta T_{{{\text{ln}}}} , \\ \Delta T_{{{\text{ln}}}} & {\text{ = [(}}T_{{{\text{out,hot,ext}}}} - T_{{{\text{in,cold,ext}}}} {\text{)}} - {\text{(}}T_{{{\text{in,hot,ctr}}}} - T_{{{\text{out,cold,ctr}}}} {\text{)]/}} \\ & \quad {\text{ln[(}}T_{{{\text{out,hot,ext}}}} - T_{{{\text{in,cold,ext}}}} {\text{)/(}}T_{{{\text{in,hot,ctr}}}} - T_{{{\text{out,cold,ctr}}}} {\text{)],}} \\ \end{aligned} $$\end{document} A HEX 2 Q M U 2 C p T in,hot,ctr T in,cold,ext T out,hot,ext T out,cold,ctr 13 25 100 13 \documentclass[12pt]{minimal}
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$$ {\text{TE = (}}T_{{{\text{out,cold,ctr}}}} - T_{{{\text{in,cold,ext}}}} {\text{)/(}}T_{{{\text{in,hot,ctr}}}} - T_{{{\text{out,cold,ctr}}}} {\text{)}}{\text{.}} $$\end{document} 13 14 14 \documentclass[12pt]{minimal}
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$$ {\text{HR = (}}T_{{{\text{out,cold,ctr}}}} - T_{{{\text{in,cold,ext}}}} {\text{)/(}}T - T_{{{\text{in,cold,ext}}}} {\text{)}} \times {\text{100\% ,}} $$\end{document} 12 T ln 14 T in,hot,ctr 12 13 14 T Specific limiting performance case scenarios depend on media type and inlet feed temperature. Higher inlet feed temperature (60°C) is worst case for the cooling HEX since the recuperator removes less heat from sterile medium. Lower inlet feed temperature (15°C) is worst case for the recuperator since it represents the greatest challenge to HR. 58 13 1 10 A sanitary design was utilized with a continuous sheet for coil formation, a tapered channel transition for the medium inlet and outlet, external bracing of shell connections, back-welding of the center pocket stiffener as much as possible, elimination of additional center stiffeners, and polishing/cleaning of all internal welds. Process connections were 150 psig bolted, milled, lap-joint flanges possessing a right angle rather than a bevelled edge to line up directly with the gasket and avoid crevices. A solid 316 L stainless steel door eliminated a process side weld around the center nozzle required to attach a stainless steel skin to a carbon steel door. 71 U 98 55 106 6 Hot water heating loop A hot water or tempered heating loop involves indirect heating without direct steam contact, and it utilizes a HEX, expansion tank, and circulation pump to heat water to above 150°C. It is more expensive than direct steam injection since additional equipment is required, but hot water loops have some key advantages. 79 97 77 83 15 p 5 77 45 97 82 5 Based on its advantages for media sterilization, indirect heating via a hot water loop was implemented. A shell and tube 316 L stainless steel HEX was selected for this application since a spiral HEX was not found to be cost-effective for the size required. The hot water loop utility piping, originally carbon steel, exhibited substantial amounts of iron oxide corrosion due to its operation at higher temperatures. This build-up throughout the hot water loop was subsequently removed by a citric acid wash and piping was replaced by stainless steel. The hot water loop was designed for an operating temperature of up to 160°C and pressure of 75 psig using compressed air (>80 psig) applied to the expansion tank. Installation of a computer limit of 160°C for the loop temperature was necessary to avoid inadvertent system over-pressurization since the steam control valve opened fully during initial loop heat up. 82 27 91 27 56 107 70 Retention loop U U U 96 U 35 Flow and pressure control 1 f 2 1 96 96 2 107 6 64 3 Table 3 Optimized tuning constants for sterilization of test media Parameter K p T 1 T 2 Flow control valve after centrifugal feed pump (40–100 lpm) 0.08 0.05 0 Pressure control valve on suction of booster pump  40–60 lpm 0.05 0.30 0  80–100 lpm 0.05 0.20 0 Flow control valve after centrifugal booster pump (40–100 lpm) 0.045 0.05 0 Hot water temperature control of retention loop inlet—sterilization temperature of 135–150°C cleaning temperature of 60–80°C (40–100 lpm) Primary (outer) 0.36 0.5 0.225 Secondary (inner) 20.0 20.0 0.20 Pressure control after process cooler—Moyno or centrifugal inlet feed pump  40–60 lpm 0.05 0.10 0  80–100 lpm 0.05 0.08 0 Pressure control after “flash” cooler—Moyno or centrifugal inlet feed pump  40–60 lpm 0.05 0.10 0  80–100 lpm 0.05 0.08 0 Temperature control of process cooler cooling to 35°C 1.5 1.0 0.25 Temperature control of “flash” cooler-during sterilization cooling to 35°C and with 35°C inlet feed (40–100 lpm) 1.5 1.0 0.25 Temperature control of “flash” cooler-during cleaning solution cooling to 60°C and with 60°C inlet feed  60 lpm 0.48 1.35 0.5  80–100 lpm 1.5 1.0 0.25 T 2 f 2 T 2 T 1 Switching valve station 1 1 Isometric design of the switching station was challenging since several automatic valves with actuators were located in close proximity to reduce dead legs. Actuator size was minimized by sizing appropriately with little excess buffer for the facility instrument air pressure. Limit switches were avoided to save additional space as well as to streamline installation and maintenance costs. Instrumentation 4 Table 4 Instrumentation Parameter Model Features Temperature Rosemount 3144PD1A1NAM5C2QPX3 0–200°C (hot water loop) 0–160°C (all others) Flow Micromotion R100S128NBBAEZZZZ 0–120 lpm Pressure Rosemount 3051CG4A22A1AS1B4M5QP f 2 f 2 Conductivity Rosemount 225-07-56-99LC/54EC-02-09 0–100 MS/cm triclamp connection Rosemount 403VP-12-21-36/54EC-02-09 0–100 μS/cm triclamp connection Temperature control Fisher-Rosemount 1052-V200-3610J Software limit of 160°C for hot water loop Flow control Fisher-Rosemount 1052-V200-3610J Flow control valves usable with either transmitter Pressure control Fisher-Rosemount 1052-V200-3610J Software adjustment to prevent full closing of system back-pressure valve Steam control Fisher-Rosemount 667-EZ-3582 125 psig unregulated plant steam supply I/P transducer Marsh-Bellofram 966-710-101 3–15 psig compact Solenoid Asco series 541 multifunction ISO 1 mono stable Spring-return piston actuators F o R o 92 86 f 2 39 Accurate measurement of volumetric flow was critical to ensuring that medium was properly sterilized for the appropriate residence time. A back-up flowmeter was installed for confirmation. Coriolis meters (Micromotion; Rosemount, Chanhassen, MN, USA), with a meter accuracy of ±0.5% of flowrate (loop accuracy of ±0.6% of flowrate), were selected rather than magnetic meters. Since flow measurements were based on fluid density, Coriolis meter readings were similar for both deionized and process (city) water (<±0.5 lpm at 60–100 lpm) and within expected variations. Coriolis meters also were insensitive to media composition changes, specifically the switch from media to water, assuming these changes negligibly affected fluid density and were not affected by the hydraulics of medium to water switches. However, volumetric flow rate readings were up to 5.5% higher after the recuperator than before it owing to density decreases with temperature for specific medium types. [Mass flowrate (kg/min) readings were similar]. Finally, since air bubble entrainment altered density readings and thus Coriolis flowmeter readings, a variable speed agitator (5:1 turndown) was installed on the larger non-sterile medium feed tanks. For soluble media, shutting off the agitation also minimized air entrainment. Proper Coriolis flowmeter installation was critical to performance. The preferred orientation was in a vertical upward flow section of pipe so that the flag filled and drained completely. Alternatives were not attractive: in the horizontal position pointing downwards the flag does not drain, in the horizontal position pointing upwards the flag incompletely fills due to air entrapment, and in the vertical position in a downward flow section of pipe the flag incompletely fills owing to gravity drainage. It also was necessary to secure the surrounding pipe to minimize interfering vibrations. 1 93 Control system Strategy The control system strategy utilized minimal sequencing with manual operation preferred both to reduce installation expense and maximize flexibility. The system was composed of about 100 I/O (input/output) with about 55% analog input/output (AI/AO) and 45% digital input/output (DI/DO). The controls were interfaced to an existing Honeywell Total Distributed Control 2000/3000 hybrid system using newly-installed, dual (redundant) Honeywell High performance Process Manager controllers. Field-mounted (remote) I/O was installed inside a Nema 4× enclosure. Calculated values by the control system Several calculated values were displayed on the HMI to permit alarming and trending. These parameters included the temperature difference (inlet minus outlet) across the insulated retention loop, flowrate difference across the recuperator (upstream minus downstream), conductivity difference (inlet minus outlet), and pressure difference across the recuperator (outlet of hot side minus inlet of cold side). In addition, the totalized volumetric flowrate was calculated based on flowmeter readings rather than using the flow transmitter totalizer signal since implementation of the former was more straightforward. F o R o E a R o F o 34 E a F o 105 E a R o 17 53 F o R o 16 16 \documentclass[12pt]{minimal}
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$$ {\text{New PV = Old PV (1}} - {\text{FV) + Measured PV (FV)}}{\text{.}} $$\end{document} F o R o V s t R 5 a b R o F o 91 Table 5 F o R o t R  Method F o Error (%) R o Error (%) a Integrate at 1 min residence time intervals 439.93 Basis 31.84 Basis b Use average of inlet and outlet loop temperatures 437.00 0.67 31.82 0.06 c Average separate calculations using inlet and outlet loop temperatures 445.62 1.30 31.88 0.13 Tuning constants and control variation K P, T 1 T 2 3 System performance Water and media testing The three types of media tested were water [both deionized (DIW) and process (city)], 55 wt.% cerelose and 50 vol.% glycerol. Heating of non-sterile feed tanks by external jacket platecoils and recycling of cooled effluent back to the system inlet permitted system testing with feeds of differing temperatures over the range of 15–60°C. “Once-through” testing was used only for cerelose to reduce Maillard reactions, which were feared to soil sterilizer internals. Water and glycerol were recycled by setting the “flash” cooler temperature to the desired inlet temperature, permitting testing of process cooler performance at or above inlet feed temperatures. The manner in which readings were taken affected assessment of their variability; readings were observed for a few seconds, then a mental average was taken and evaluated to determine whether the bounce was within reasonable limits. Computer system historical trends, which recorded data every 1 min also were used to assess variability. 71 f 9 1 6 7 8 Table 6 System performance using water at 100 lpm (900 L retention volume unless noted otherwise) Parameter Feed inlet of 15°C Feed inlet of 25°C Feed inlet of 60°C Design Observed Moyno/centrifugal Design Design Observed Moyno/centrifugal Observed Moyno 540 L Recuperator cold side inlet feed (°C) 15.0 15/15 25.0 60.0 59/59 60 Recuperator cold side outlet/heater hot side inlet (°C) 126.0) 120/120 128.0) 135.0) 131/132 131 Heater hot side outlet/retention loop inlet (°C) 150.0 150.1/150.0 150.0 150.0 150.0/150.0 150.01 Retention loop outlet/recuperator hot side inlet (°C) 150.0 149.2/149.1 150.0 150.0 149.2/149.1 149.02 Recuperator hot side outlet/process cooler hot side inlet (°C) 39.6) 46/43 47.6) 75.4) 80/78 77 Process cooler hot side outlet (°C) 35.0 35.0/35.0 35.0 35.0 35.0/35.1 34.8 Process cooler cold side inlet (°C) 6.0 8.6/8.2 6.0 6.0 8.3/N/A N/A Process cooler cold side outlet (°C) 8.5) 41/50 11.6) 11.4) 49/N/A N/A 14 82.2) 77.7/77.8 82.4) 83.3) 79.1/80.2 78.9 12 4.57) 3.49/3.68 4.62) 4.93) 3.68/4.05 4.06 13 4.63) 3.60/3.61 4.68) 5.00) 3.96/4.27 3.94 (1) Water not tested at 25°C but design is included for comparison. (2) Process cooler inlet temperature reading taken from building chilled water supply temperature. (3) Design numbers calculated based on intermediate temperatures needed to reach 150°C at the retention loop inlet assuming that most of the load was undertaken by the heating HEX based on a maximum heating loop temperature of 160°C. Thus, less than the maximum area of the recuperator was utilized in some cases. (4) Design numbers in bold calculated based on 100% utilization of the recuperator surface area and permitting the hot water loop to operate at values less than 160°C Table 7 System performance (900 L retention loop volume) using 55 wt.% cerelose at 65 (25°C inlet temperature) and 100 lpm (60°C inlet temperature) Parameter Feed inlet of 25°C Feed inlet of 60°C Design Observed Moyno/centrifugal Design Observed Moyno 65 lpm 65 lpm 40 lpm 100 lpm 100 lpm 40 lpm Recuperator cold side inlet feed (°C) 25.0 25 25/26 60.0 57 60 Recuperator cold side outlet/heater hot side inlet (°C) 110.5 120 126/125 127.0 127 130 Heater hot side outlet/retention loop inlet (°C) 150.0 150.0 150.0/150.0 150.0 150.0 150.0 Retention loop outlet/recuperator hot side inlet (°C) 150.0 148.8 148.1/147.9 150.0 149.1 148.1 Recuperator hot side outlet/process cooler hot side inlet (°C) 64.5 54 47/51 86.3 82 77 Process cooler hot side outlet (°C) 35.0 35.7 35.1/34.3 35.0 35.0 35.8 Process cooler cold side inlet (°C) 6.0 8.2 7.5/NA 6.0 7.7 (est) 7.7 Process cooler cold side outlet (°C) 13.3 40 42/NA 21.1 61.4 (est) 45 14 68.4 76.0 80.8/79.8 74.4 75.3 77.8 12 2.17) 3.29 4.58/4.13 2.72) 2.98 3.99 13 2.17 3.30 4.57/4.32 2.91 3.17 3.86 Est 6 Table 8 System performance (900 L retention loop volume) using 50 vol.% glycerol at 88 lpm using flowmeter after inlet feed pump (15°C inlet temperature) and 91.5 lpm (60°C inlet temperature) Parameter Feed inlet of 15°C Feed inlet of 60°C Design Observed Moyno Design Observed Moyno/centrifugal 88 lpm 88 lpm 40 lpm 91.5 lpm 91.5 lpm 40 lpm Recuperator cold side inlet feed (°C) 15.0 15 15 60 60/60 60/60 Recuperator cold side outlet/heater hot side inlet (°C) 116.0 114 117 128.3) 128/128 130/130 Heater hot side outlet/retention loop inlet (°C) 150.0 150.0 150.0 150.0 150.0/150.0 150.0/150.0 Retention loop outlet/recuperator hot side inlet (°C) 150.0 149.1 147.9 150.0 149.1/148.9 147.9/148.1 Recuperator hot side outlet/process cooler hot side inlet (°C) 49.0) 52 48 81.7) 82/80 76/76 Process cooler hot side outlet (°C) 35.0 34.9 34.6 35.0 35.0 (est)/60.2 62.44/60.2 Process cooler cold side inlet (°C) 6.0 8.1 7.66 6.0 7.8/7.89 7.6/7.83 Process cooler cold side outlet (°C) 17.6) 38.5 43.0 13.9) 45.2 (est)/73 78/72 14 74.8) 73.3 75.6 75.9) 75.6/75.6 77.8/77.8 12 2.97) 2.75 3.19 3.16) 3.16/3.32 4.14/4.11 13 2.97) 2.82 3.30 3.16) 3.23/3.25 3.92/3.87 Est T ln Q M C p T 6 Observed temperature profiles, HRs, NTUs, and TEs generally met or were somewhat lower than design depending upon which design basis was utilized. The primary factor causing under-performance was believed to be lack of allowance for the gap that was likely present even with pliable, full-face gaskets installed owing to unavoidable variations in flatness of the HEX spiral and door faces. The observed hot side recuperator inlet temperature from the non-adiabatic retention loop was lower than the isothermal design assumption and thus raised measured values compared with design HR, NTU, and TE. Viscosity decreases with higher temperature resulted in improved performance. System draining hold up volume The system’s hold up volume was established by running process water into a completely drained and air-blown system. It was determined when water reached a certain section by opening the adjacent downstream drain valve. Measured hold up volumes agreed with calculated ones within reasonable limits but may have been affected by the ability to fill the system completely at the lower flowrates used to obtain these measurements. Overall, the impact on design residence times of these differences was negligible, however. Inlet feed stream and outlet distribution stream switching Prior to testing all instrument air connections to the switching skid were checked for leaks and proper venting. When switching to the distribution manifold (sterilizer feed to fermenters) from either the sewer or recycle flow paths, transient flow and pressure spikes and their effect on inlet and outlet retention loop temperatures were observed and found to be negligible. When sterilizer distribution was switched from the receiving waste tank to the desired fermenter vessels, pressure spikes also had a negligible effect on temperature. Minimal disturbances were observed for actual water-to-media switch over when the system feed was changed from water to 55 wt.% cerelose and back again. In all of these instances, an acceptable temperature spike was considered to be less than the variation observed during normal flow operation. Since these spikes were negligible, it was not necessary to flush the system appreciably after a switch to regain steady performance. In addition, sewer to recycle, waste to sewer, and fermenter to waste transitions were not potential sterility risks since these typically occurred after sterilized medium transfer was completed. Heat losses 2 55 6 100 99 System sensitivity f 2 F o R o F o F o D R o R o R o F o R o Dimensionless groups and axial dispersion N Re N Bs 9 10 Table 9 Key calculated parameters for the retention loop for an inlet feed temperature of 15°C, sterilization hold temperature of 150°C, and process cooler set point of 35°C (L/D of 9,318 for 900 L retention loop volume) Parameter Water (40–100 lpm) 55 wt.% cerelose (40–65–100 lpm) 50 vol.% glycerol (40–88–100 lpm) N Re 84,000–210,000 53,000–86,000–132,000 60,600–133,300–151,500 V 0.305–0.762 0.335–0.518–0.823 0.335–0.701–0.792 f 11 0.0222–0.0204 0.0232–0.0221–0.0213 0.0231–0.0212–0.0209 D z VD 0.5 61 10 0.532–0.510 0.544–0.531–0.521 0.543–0.520–0.516 D z 2 0.00890–0.0213 0.0100–0.0151–0.0235 0.00999–0.0200–0.0224 N Bs VL D z 17550–18300 17150–17550–17900 17150–17950–18100 Water D z VD 61 N Re 4 N Re 5 D z 2 N Re 4 N Re 5 N Bs D z N Re 4 N Re 5 ε −5 D ε D 78 N Re N Bs Table 10 Calculated bulk velocities of HEXs for various test media (based on 40–100 lpm process flowrate, sterilization temperature of 150°C, process cooler set point of 35°C) HEX Process side velocity (m/s) Utility side velocity (m/s) Water (15°C inlet feed) 55.0 wt.% cerelose (25°C inlet feed) 50 vol.% glycerol (15°C inlet feed) Interconnecting piping 0.47–1.26 0.47–1.33 0.47–1.32 N/A Recuperator (both sides) 0.35–0.94 0.34–0.94 0.34–0.98 N/A Heater 0.24–0.62 0.25–0.66 0.25–0.67 2.0 Retention loop 0.31–0.77 0.32–0.81 0.32–0.80 N/A Process and “flash” coolers 0.35–0.87 0.35–0.89 0.35–0.88 3.3 ρ p 3 3 N Re 9 11 f D z 10 N Bs 9 61 N Bs 9 N Bs t R 3 Fig. 3 a b  Steam-in-place testing f 2 82 47 82 69 47 82 92 Operational testing was performed to test both the steam sterilization-to-water transition and water sterilization modes. Regardless of the sterilization method used, prior steam sterilization of the empty system and subsequent switching back pressure control from the “flash” to process cooler was required. Each method had key points requiring extra care- the initial water introduction for the steam sterilization-to-water transition and placing the empty non-sterile side of the recuperator on-line for the water sterilization. Thus, the time and attention required to execute either method was reasonably equivalent. F o Clean-in-place (CIP) testing 19 71 3 24 10 40 38 38 Conclusion Improvements implemented for a next generation, pilot-scale continuous sterilization system span the design, fabrication, and testing project phases and have been described. Advantages and disadvantages of various system features were evaluated based on literature analysis from fermentation as well as other related applications. Successful realization of these requirements depended on the adoption of an effective project strategy. The selected system vendor had experience primarily with the food industry since there were few new media sterilizers for manufacturing being constructed and even fewer for pilot plant process development use. Thus, it was critical to devote sufficient time to comprehensively determining system requirements. Development of a detailed sequence of operation as the piping and instrument diagram (P&ID) itself was developed ensured alignment of performance expectations. In addition, selection of a system (as well as HEX) vendor who was located nearby facilitated interim progress examinations prior to delivery. The “worst case” design scenarios were determined carefully, ensuring that they did not create unnecessary additional costs. Agreement on the design assumptions and performance requirements was critical, particularly for calculated quantities. Specifically, the entire system operation needed to be evaluated when developing the HEX performance requirements. Interim temperatures and pressures were estimated based on the system’s flow connections and not simply considering each HEX separately. Since the temperature rise in each HEX stream depended on actual flowrate, design calculations were done using expected flowrates and not solely the maximum flowrates that the HEX can support. Finally, a check of calculations for the various design cases ensured they were internally consistent. Performance testing was devised to quantify actual operation versus design expectations. Intermediate pressure and temperature measurements within the system were compared to design calculations to identify performance issues. Communication of acceptable variability to the control and instrument system designer upfront ensured proper test criteria were met and steady state variations were acceptable. Tests were performed and documented for all operational phases. These system tests were considered critical to effectively characterizing the system’s capabilities prior to placing the equipment in service.