Flow Measurement and Process Control Solutions for a Biotechnology Company

A biotechnology company specializing in the pharmaceutical field produces monoclonal antibodies, recombinant proteins, vaccines, and other products. Its production process includes key steps such as fermentation, purification, formulation, and filling, with extremely high requirements for precision, hygiene, and reliability to meet GMP and FDA regulatory standards.

Based on the customer's process requirements, Sure Instrument provided the following combination of flow measurement and process control instruments:

1. Temperature Transmitters (190 units)

• Fermentation Tanks: In large bioreactors, temperature is a critical parameter affecting cell activity and product expression. The temperature transmitters are embedded in the tanks to monitor temperature gradients at different depths in real-time, ensuring that microbial or mammalian cells remain within the optimal metabolic temperature range (with ±0.5% precision). The sensors are made of 316L stainless steel, meeting the 3A sanitary standard and capable of withstanding high-temperature steam sterilization (operating temperature -50°C to 200°C, with long-term tolerance of 140°C SIP sterilization cycles).

• Purification System: During the elution phase of chromatography columns, temperature fluctuations can lead to protein denaturation. The transmitters are linked to temperature control modules via 4-20mA signals to maintain a constant temperature of the chromatographic medium, ensuring the stability of the target product. Response time is less than 1 second, with an IP69K protection rating.

2. Ultrasonic Level Meter (1 unit) and Radar Level Level Meter (6 units)

• Ultrasonic Level Level Meter: Installed at the top of raw material storage tanks, it monitors the liquid levels of culture media, buffers, and other materials. Its non-contact measurement method avoids direct contact with materials, eliminating the risk of cross-contamination, especially suitable for culture media storage tanks containing surfactants, avoiding the risk of traditional float-type instruments getting stuck.

• Radar Level Level Meter: Deployed in finished product storage tanks and high-risk reagent tanks (such as strong acids and bases), it uses 80GHz high-frequency microwave technology (measurement accuracy ±1mm) to penetrate steam or dust inside the tank for continuous level monitoring. During the CIP (Clean-In-Place) process, it provides real-time feedback of cleaning agent levels via Modbus RTU communication, and withstands high temperatures of up to 150°C during steam sterilization, preventing equipment dry-burning caused by incorrect level readings.

  

3. Ultrasonic Flow Meters (12 units) and Electromagnetic Flow Meters (4 units)

• Ultrasonic Flow Meters: Mainly used in the circulation pipelines of Purified Water (PW) and Water for Injection (WFI) systems. The obstruction-free design (pressure drop < 0.01bar) avoids pressure loss caused by traditional mechanical flow meters. With a wide range ratio of 30:1, it meets both low-flow cleaning and high-flow production needs. In buffer solution transfer, the bidirectional flow measurement function supports precise control of forward and reverse flushing processes.

• Electromagnetic Flow Meters: Specifically designed for the quantitative transfer of conductive liquids (such as culture media and acid-base solutions). Equipped with PTFE lining and tantalum electrodes, they withstand highly corrosive liquids with a pH range of 1-14 (such as chromatography elution liquids). In culture media transfer, they achieve ±0.2% precision quantitative control via pulse output (with repeatability of ±0.1%).

  

4. Vortex Flow Meters (19 units) and Coriolis Mass Flow Meters (2 units)

• Vortex Flow Meters: Used for flow monitoring of clean compressed air, nitrogen, and other gases (range: gas 0.3-35m/s, steam 2-75m/s). In fermentation processes, they optimize dissolved oxygen levels (DO values) by measuring inlet gas flow. In lyophilization systems, they monitor inert gas flow to prevent drug oxidation. The built-in temperature compensation function eliminates measurement deviations caused by changes in gas density, automatically converting actual flow to standard flow (with ±1.0% accuracy).

  

• Coriolis Mass Flow Meters: Applied in the final metering of high-value liquid pharmaceuticals on filling lines (such as monoclonal antibodies and mRNA vaccines). They directly measure mass flow instead of volumetric flow, unaffected by changes in liquid viscosity (such as mRNA vaccine liposomes) or temperature, with a precision of ±0.1%. Dual-parameter output (mass flow + density) can be used for online detection of drug concentration, avoiding batch rejection due to underfilling or overfilling. The dual-U-tube design withstands a viscosity range of 1-2000 mPa·s, and combined with online density detection (±0.001g/cm³), it ensures filling error of less than ±0.5mg per vial.

5. pH Meters (9 units) and Oxidation-Reduction Potential (ORP) Meters (10 units)

• pH Meters: In fermentation tanks, they monitor real-time pH fluctuations caused by cell metabolism and automatically adjust the operation of acid and base addition pumps via PID algorithms. The retractable electrodes (with automatic mechanical cleaning and IP68 protection) prevent measurement drift caused by cell debris or protein adhesion. They monitor the pH range of 4-10 in fermentation tanks (with ±0.02 precision), and are linked to acid and base dosing pumps via 4-20mA + digital communication, with a response time of less than 5 seconds.

  

• ORP Meters: Used to monitor the oxidation-reduction state in cell culture environments (e.g., the sensitivity of CHO cells to dissolved oxygen and reducing substances). The electrodes are made of platinum with Ag/AgCl reference electrodes, designed to resist biological contamination. The signal output is linked to the oxygen supplementation system, with a measurement range of -1500mV to +1500mV. Through PID control of oxygen supply rate, they maintain the optimal metabolic state of CHO cells.

6. Pressure Transmitters (284 units)

• Ultrafiltration (UF/DF) System: They monitor transmembrane pressure differences (TMP) and dynamically adjust the feed pump speed through 0.1% precision signal feedback to prevent membrane fouling or rupture. TMP control error is less than 0.05bar.

• Formulation Tanks: During the formulation of vaccine adjuvants, pressure signals are used to detect pipeline blockages or leaks, triggering DCS system alarms and activating backup circuits to ensure the integrity of the sterile environment. Vacuum tolerance: -1 to 10bar.

7. Metal Tube Float Flow Meters (2 units)

• Used for the precise dosing of low-flow additives such as silicone oil and defoamers. The vertical installation design (pressure tolerance of 16bar, medium temperature -80°C to +200°C) is used for the micro-dosing of silicone oil (range 0.1-5 L/min). The magnetic coupling drive structure eliminates leakage risks, and the scale is NIST traceable (with ±2% reading accuracy), meeting GMP requirements for manual verification. The self-powered feature makes them suitable for explosion-proof areas or emergency manual operation scenarios.

Implementation Results

Through the customized instrument solution, the customer achieved:

• Data Integrity: All instruments provide Class 3.1 calibration certificates, meeting FDA audit requirements.

• Risk Controllability: Key equipment (such as Coriolis mass flow meters) are SIL2 certified, supporting safety interlocks.

• Maintenance Cost Optimization: Non-contact instruments such as ultrasonic and radar flow meters reduce cleaning downtime frequency, resulting in a 22% decrease in annual maintenance costs.

Industry Expansion Value

This case study demonstrates the three core values of flow measurement technology in the biopharmaceutical field:

• Risk Control: Redundant sensor design prevents batch rejection caused by single-point failures.

• Process Scale-Up Support: High-precision instruments provide data foundations for scaling up from laboratory to commercial production.

• Compliance Assurance: Instrument materials (316L stainless steel, PTFE lining) meet ASME BPE standards and pass GMP audits.

The biopharmaceutical industry is moving towards continuous processing. Our company will continue to develop intelligent instruments with integrated SIP (Sterilization-In-Place) and digital calibration functions to help customers build next-generation Biopharma 4.0 factories.