E03 - Aseptic Processing Technology 2008 Case Study: Application of Peristaltic Filling for Flexibility and Accuracy by Ted Kemnitz Automated Machine Technologies, Inc. AMT (919) 361 0121 Ted.Kemnitz@AMTLiquidFilling.com
Introduction to Servo Peristaltic Liquid Filling Liquid filling is a major element of Aseptic Processing Technology. This presentation highlights the advantages of using Servo Peristaltic Filling for Flexibility wide range of products and fill volumes Accuracy better than 0.5% with Servo Compensation Disposable Technology best suitable, minimal expense of product contact parts Lowest Contamination Risk - only peristaltic tubing contacts the product Piggyback System - easy and cost-effective integration into existing infrastructure
Aseptic Liquid Filling Desired Essentials Consistent Accuracy and Precision maintained throughout entire production with minimal set up Reduced risks of contamination with the lowest number of product contact parts that are easily exchangeable and can be disposable Eliminated dripping after fill via suck-back system Reduced splashing during fill by optimizing process parameters, such as number of nozzles, dispensing flow rate, nozzle and tubing sizes, bottom-up filling Flexibility with easy changeover to different products and fill volumes
Aseptic Liquid Filling - Desired Essentials Ability to interface with automatic SPC and PID process for 100% weight feedback Reduced risk of operator errors by utilizing exchangeable sets of fixed tooling in place of manual adjustments User-friendly operation based on simplicity and low maintenance Rugged system with long term consistency and reliability resulting in reduced downtime Easy integration with existing technologies and existing infrastructure for economical viability
Fig. 1. Servo Peristaltic Liquid Filling
Fig.2. Servo Peristaltic Liquid Filling Machine Cantilever type
Fig. 3 Servo Peristaltic Liquid Filling Machine Guards removed
Fig. 4. Servo Peristaltic Liquid Filling Machine Top view
Fig. 1. Servo Peristaltic Liquid Filling
Fig.5. Servo Peristaltic Liquid Filling Principle
Fig.6. Servo Peristaltic Pump Flow Characteristic
Servo Peristaltic Compensation - Principle Example: Integrating 0.340 ml Dispense
Technology Base - 1994 Incorporated in 1994 as Automated Machine Technologies, Inc. (AMT ), a manufacturer of packaging machines. Driven by demand for cost effective, high performance Servo motion controllers In-house Servo technology development, patents obtained Towards the end of XX century Computer Programmable Servo Systems were evolutionary breakthrough for high performance packaging machines.
CCL Industries, Toronto ON Development of environmentally friendly aerosol system 330 parts per minute citric acid dispensing precision of 0.5% Wide range of fill volumes, 0.2 ml up to 12 ml Easy changeover and easy cleaning Original solution was urgently needed. While working with the new aerosol system, coincidently, an ideal product for Aseptic Liquid Filling was created.
Ciba Corning Diagnostic, Walpole MA Pilot production for diagnostics research High fill precision and easily programmable changeover to many different products and sizes Easily removable product contact parts for autoclaving Adjustable diving nozzles with bottom-up control An answer was given to the demanding Ciba Corning needs with a two-axis servo peristaltic liquid filling machine and with a linear actuator for programmable nozzles.
Organon Technika, Durham NC Sterile liquid filling, stoppering and screw capping integrated into one system One system for over a hundred different products Precise and aseptic liquid dispensing over wide range from 0.5mL to 1L Programmable calibration and changeover The flexibility of the Servo peristaltic pump became apparent when it was incorporated into the multifunctional monoblock system.
UDL Laboratories, Largo FL A manufacturer of Unit Dose Liquid Packs Existing system required frequent and difficult adjustments of all 40 individual pistons Lack of fill precision Difficulty in cleaning piston cavities from sugarbased product Dripping nozzles due to low surface tension Problem meeting FDA regulations Large project on-hold until a solution could be found Servo peristaltic dispenser with compensated flow characteristic was the only answer to the complex demand for filling UDL Unit Dose Liquid Packs. Simplicity of the hardware allowed to build the custom machine economically and in a timely manner, saving the multimillion-dollar project. In fiscal year 2005, UDL shipped over 800 million doses and ranked as the number one generic unit dose supplier.
biomerieux, Durham NC A manufacturer of BacT/ALERT blood culture bottles Replacing glass container and 30mm stopper with new, cost-effective plastic vial with 20mm stopper for diagnostic blood culture bottles Filling through stoppers with 12 piercing nozzles in aseptic production Smaller stoppers require precise positioning of vials under piercing needles Easy changeover Increased fill precision Reduced risk for contamination With multi-axis capabilities, the Servo Peristaltic Pump was successfully integrated with a Servo-driven timing screw to precisely position the bottles under the needles.
biomerieux, Durham NC Servo Peristaltic Dispenser - Automatic SPC with 100% pre-fill/post-fill weight feedback
biomerieux, Durham NC A manufacturer of BacT/ALERT blood culture bottles Problems on the main production line: High maintenance Dripping nozzles Complicated and time-consuming adjustments Difficulties to maintain precise fill weights of +/-1% over 16 hours of continuous production cycle Disposable Technology and high fill precision at production rates over 300 vials per minute demanded SOLUTION: - Cantilever Servo pump for Disposable Technology - Nozzle-to-nozzle equalizing system with feedback - Automatic tubing wear compensation - Increased fill precision was maintained over 16 hour runs, and need for manual calibration was eliminated - Daily maintenance was reduced from hours to only a few minutes - FDA requirements were easily met with disposable product contact parts One year later, on November 26, 2007, biomerieux reported a 10% annual growth in the blood culture market.
biomerieux - Servo Peristaltic Data 4.0 3.0 2.0 1.0 Variation [%] Silicone Tubing Grade Preformance on AMT 20-Nozzle Peristaltic Filler 1/8" ID Tubing @ 4 grams 0.0-1.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20-2.0-3.0-4.0 2.02% Sani-Tech 50 Standard Grade Silicone Tubing Part No. STHT-C-125-4 3.72% Cole-Parmer Standard Grade Silicone Tubing Catalog No. K-95802-06. 2.26% Amesil Standard Grade Silicone Tubing Part No. ASTP125-4ELPF. 0.14% Dow Corning Pharma Advanced Nozzle # biomerieux: Servo Peristaltic Machine Model 239
Siemens Medical Solutions, Walpole MA Diagnostic Reagent Facility Expansion Increased and sustained fill precision throughout prolonged aseptic production On the fly calibration Monitoring of fill weights with the use of an automatic sampling system for SPC -- The Servo Peristaltic pump was the answer to - sustained precision and sterility -- The nozzle servo-mechanism was upgraded with - horizontal movements for automatic sampling A robust growth in the immunodiagnostics business is projected.
Siemens Medical Solutions - Servo Peristaltic Data 30.02 30 29.98 Weight [G] 30 G fills with 8 nozzles 29.96 29.94 29.92 29.9 29.88 29.86 29.84 Series1 Series2 Series3 Series4 Series5 Series6 Series7 Series8 Sample # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Servo Peristaltic Machine Model 150
Siemens Medical Solutions - Servo Peristaltic Data 0.250 0.200 0.150 0.100 0.050 [%] 100%*(Sample-Mean)/Mean 30 G fills with 8 nozzles Series1 Series2 Series3 Series4 Series5 Series6 Series7 Series8 0.000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30-0.050-0.100-0.150-0.200 Sample# Servo Peristaltic Machine Model 150
Siemens Medical Solutions - Servo Peristaltic Data 1.0 0.8 0.6 Variation [%] Fill Precision across 4 Nozzles 1/32" ID Tubing @ 0.5 grams 0.4 0.2 0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30-0.2-0.4 Sample # -0.6-0.8 0.54% Nozzle 1 0.71% Nozzle 2 0.54% Nozzle 3 0.71% Nozzle 4-1.0 Servo Peristaltic Machine Model 150
Catalent Pharma Solutions, Raleigh, NC Disposable Technology Fill Precision +/- 0.5% Flexibility with easy changeover Volumes 0.5 ml to 1000 ml Portable machine, easily integrated with Bosh TL system Cantilever Servo Peristaltic Pump was configured into a portable machine and designed for Disposable Technology.
Catalent Pharma Solutions - Servo Peristaltic Data Produced: 02/04/08 Sample Deviation [G] [%] 1 5.004-0.022 2 5.007 0.038 3 5.004-0.022 4 5.006 0.018 5 5.004-0.022 6 5.008 0.058 7 5.005-0.002 8 5.003-0.042 9 5.004-0.022 10 5.003-0.042 11 5.005-0.002 12 5.005-0.002 13 5.003-0.042 14 5.007 0.038 15 5.004-0.022 16 5.006 0.018 17 5.003-0.042 18 5.005-0.002 19 5.003-0.042 20 5.004-0.022 21 5.007 0.038 22 5.004-0.022 23 5.006 0.018 24 5.003-0.042 25 5.008 0.058 26 5.006 0.018 27 5.006 0.018 28 5.007 0.038 29 5.005-0.002 30 5.008 0.058 Mean 5.005 0.500 0.400 0.300 0.200 0.100 0.000-0.100-0.200-0.300-0.400-0.500 5.050 5.040 5.030 5.020 5.010 5.000 4.990 4.980 Variattion [%] Fill Precision 1 Nozzle 1/16 ID tubing @ 5 grams 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Fill Weight [g] Fill Weights 1 Nozzle 1/16 ID tubing @ 5 grams Sample # 4.970 4.960 4.950 Sample # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Catalent Pharma Solutions - Servo Peristaltic Data Produced: 02/13/08 0.200 [%] 100%*(Sample-Mean)/Mean 12 Nozzle Servo Peristaltic Model 246 5 [G] dispense 0.150 0.100 0.050 0.000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30-0.050-0.100-0.150-0.200 Sample # Nozzle 1 Nozzle 2 Nozzle 3 Nozzle 4 Nozzle 5 Nozzle 6 Nozzle 7 Nozzle 8
Fig. 7. 20-Nozzle Servo Peristaltic System
Fig. 8. Piggyback Servo Peristaltic Dispenser incorporated into Filling & Stoppering Monoblock Machine
Fig. 9. Servo Peristaltic 384-Well MicroPlate Dispenser From 0.5 ul to 0.5 ml; CV=1%
Fig. 10. Servo Peristaltic MicroPlate Fig. 11. Peristaltic Micro Pump
Fig. 11. Disposable Cartridge for Servo Peristaltic MicroPlate Dispenser
120.0 Flow Rate per Nozzle [ml/sec] @220 RPM 112.9 100.0 90.6 80.0 64.4 60.0 40.0 27.9 39.0 20.0 0.0 0.3 1.2 4.7 10.5 18.2 0.031 0.063 0.125 0.188 0.250 0.313 0.375 0.500 0.625 0.750 Tubing ID [inch] Servo Peristaltic Machine
Absolute Error [ml] 10.000 9.000 8.642 8.000 7.000 6.000 5.000 4.649 4.000 3.000 2.000 1.000 0.000 0.004 0.016 0.068 0.168 0.331 0.588 0.965 2.267 0.031 0.063 0.125 0.188 0.250 0.313 0.375 0.500 0.625 0.750 Tubing ID [inch] Servo Peristaltic Machine
250.0 Bottles per minute @ Tubing ID=1/32" 8-Nozzles 200.0 150.0 5-Nozzles 100.0 50.0 2-Nozzles 1-Nozzle 0.0 0.99 Tolerance[%] 0.59 0.40 0.33 0.30 0.28 0.27 0.26 0.25 0.24 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 Fill Volume [ml] Servo Peristaltic Machine
400.0 Bottles per minute @ Tubing ID=1/16" 350.0 12-Nozzles 300.0 250.0 8-Nozzles 200.0 5-Nozzles 150.0 100.0 50.0 0.0 2-Nozzles 1-Nozzle 1.83 Tolerance[%] 1.02 0.74 0.61 0.53 0.47 0.43 0.40 0.38 0.36 1 2 3 4 5 6 7 8 9 10 Fill Volume [ml] Servo Peristaltic Machine
Bottles per minute @ Tubing ID=3/32" 350.0 12-Nozzles 300.0 250.0 8-Nozzles 200.0 150.0 5-Nozzles 100.0 50.0 0.0 2-Nozzles 1-Nozzle 1.43 Tolerance[%] 1.12 0.94 0.82 0.73 0.66 0.61 0.57 0.54 051 3 4 5 6 7 8 9 10 11 12 Fill Volume [ml] Servo Peristaltic Machine
Bottles per minute @ Tubing ID=1/8" 350.0 12-Nozzles 300.0 250.0 8-Nozzles 200.0 150.0 5-Nozzles 100.0 50.0 0.0 2-Nozzles 1-Nozzle 1.56 Tolerance[%] 0.88 0.65 0.54 0.47 5 10 15 20 25 30 35 40 45 50 Fill Volume [ml] 0.43 0.39 0.37 0.35 0.34 Servo Peristaltic Machine
Bottles per minute @ Tubing ID=3/16" 350.0 300.0 12-Nozzles 250.0 8-Nozzles 200.0 150.0 5-Nozzles 100.0 50.0 0.0 2-Nozzles 1-Nozzle 1.88 1.04 Tolerance[%] 0.76 0.62 0.54 0.48 0.44 0.41 0.39 0.37 10 20 30 40 50 60 70 80 90 100 Fill Volume [ml] Servo Peristaltic Machine
Bottles per minute @ Tubing ID=1/4" 300.0 12-Nozzles 250.0 200.0 8-Nozzles 150.0 5-Nozzles 100.0 50.0 0.0 2-Nozzles 1-Nozzle 1.85 1.03 0.75 Tolerance[%] 0.61 0.53 0.48 0.44 0.41 0.38 0.37 20 40 60 80 100 120 140 160 180 200 Fill Volume [ml] Servo Peristaltic Machine
Bottles per minute @ Tubing ID=5/16" 250.0 12-Nozzles 200.0 8-Nozzles 150.0 100.0 5-Nozzles 50.0 0.0 2-Nozzles 1-Nozzle 1.37 1.04 0.85 Tolerance[%] 0.73 0.65 0.59 0.54 0.51 0.48 0.45 50 70 90 110 130 150 170 190 210 230 Fill Volume [ml] Servo Peristaltic Machine
Bottles per minute @ Tubing ID=3/8" 160.0 140.0 8-Nozzles 120.0 100.0 5-Nozzles 80.0 60.0 40.0 20.0 0.0 2-Nozzles 1-Nozzle 1.17 0.84 Tolerance[%] 0.68 0.59 0.52 0.48 0.44 0.41 0.39 0.38 100 150 200 250 300 350 400 450 500 550 Fill Volume [ml] Servo Peristaltic Machine
Bottles per minute @ Tubing ID=1/2" 140.0 8-Nozzles 120.0 100.0 80.0 4-Nozzles 60.0 40.0 2-Nozzles 20.0 0.0 1-Nozzle 1.33 0.96 Tolerance[%] 0.77 0.65 0.58 0.52 0.48 0.45 0.43 0.41 200 300 400 500 600 700 800 900 1000 1100 Fill Volume [ml] Servo Peristaltic Machine
Bottles per minute @ Tubing ID=5/8" 100.0 90.0 8-Nozzles 80.0 70.0 60.0 50.0 4-Nozzles 40.0 30.0 20.0 10.0 0.0 2-Nozzles 1-Nozzle 1.13 0.86 Tolerance[%] 0.72 0.62 0.56 0.51 0.47 0.44 0.42 0.40 500 700 900 1100 1300 1500 1700 1900 2100 2300 Fill Volume [ml] Servo Peristaltic Machine
80.0 Bottles per minute @ Tubing ID=3/4" 70.0 8-Nozzles 60.0 50.0 40.0 4-Nozzles 30.0 20.0 10.0 0.0 2-Nozzles 1-Nozzle 1.06 Tolerance[%] 0.82 0.68 0.59 0.53 1000 1400 1800 2200 2600 3000 3400 3800 4200 4600 Fill Volume [ml] 0.49 0.45 0.43 0.39 0.40 Servo Peristaltic Machine
0.8 Fill Precision across 4 Nozzles 1/16 ID tubing @ 1 gram Variattion [%] 0.6 0.4 0.2 0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30-0.2-0.4-0.6 0.79% Nozzle 1 0.86% Nozzle 2 0.81% Nozzle 3 0.64% Nozzle 4 Sample # Servo Peristaltic Machine
1.2 Fill Precision across 8 Nozzles 1/16" ID Tubing @3 grams 1.0 0.8 Variation [%] 0.6 0.4 0.2 0.0-0.2-0.4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30-0.6-0.8 0.530% Nozzle 1 0.632% Nozzle 2 0.606% Nozzle 3 0.577% Nozzle 4 Sample # 0.654% Nozzle 5 0.610% Nozzle 6 0.730% Nozzle 7 0.592% Nozzle 8 Servo Peristaltic Machine
0.6 Fill Precision across 8 Nozzles 1/8" ID Tubing @ 10 grams 0.4 0.2 Variation [%] 0.0-0.2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30-0.4-0.6-0.8 0.33% Nozzle-1 0.31% Nozzle-2 0.42% Nozzle-3 0.29% Nozzle-4 Sample # 0.33% Nozzle-5 0.38% Nozzle-6 0.94% Nozzle-7 0.34% Nozzle-8 Servo Peristaltic Machine
Fill Precision across 8 Nozzles 1/8" Tubing @ 30 grams 0.6 0.4 0.2 Variation [%] 0.0-0.2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30-0.4-0.6-0.8 0.88% Nozzle-1 0.85% Nozzle-2 0.86% Nozzle-3 0.84% Nozzle-4 Sample # 0.84% Nozzle-5 0.79% Nozzle-6 0.85% Nozzle-7 0.84% Nozzle-8 Servo Peristaltic Machine