New Technologies Optimize API and Drug Product Manufacturing

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Over the past several months, manufacturers pushed technological limits to release products to optimize API and drug product manufacturing processes. Some of these technologies include advancements in lyophilization, continuous flow chemistry, process control, and powder handling. Below is an assortment of such products for API and drug product manufacturing.

New systems for lyophilization

Telstar has developed LyoGistics Zero, a vial automatic loading and unloading system for freeze dryers with a contactless magnetic drive for the manufacturing of hazardous products (1). A steam-sterilizable slider uses a passive linear magnetic driving mechanism that functions without racks, belts, or bellows to reduce particle generation and improve cleanliness. The slider remains in the chamber and is cleaned and sterilized with the internals of the freeze dryer. The system is suited for aseptic isolators requiring advanced protection for the operator (Occupational Exposure Limit 5), product (ISO5), and environment.

The Lyometrics system from Telstar provides online monitoring of global batch temperature during developmental or full production conditions in GMP industrial freeze dryers with automatic loading and unloading systems (2). With the use of soft-sensor technology, the system offers a more practical approach to collecting product temperature when production environments are presented with automation and physical obstacles. The software within the freeze dryer control system can non-invasively obtain the average sublimation interface temperature of an entire product batch.

Tools for continuous flow chemistry

Titan, a modular continuous chemical processing system from Syrris, is a turnkey system for prolonged use in demanding manufacturing environments (3). It comprises a range of integrated, rapidly reconfigurable modules, enabling continuous flow processes to be performed on a laboratory scale, or at rates of up to a tonne per day. Reactors are available in 64 and 250-mL volumes and may be connected when larger-scale systems are required. The system offers high chemical resistance, and it can accommodate reaction temperatures from -40 to +250 °C and pressures up to 20 bar at flow rates between 1 and 250 mL/min per channel.

Process control solutions

The Dynatrol CL-10GP Proportional Level Detector controls liquid levels in pilot plants, pharmaceutical processing, and small vessels to obtain proportional level control over an exact range (4). The EC-103C(G) Control Unit is paired with the detector and can activate electro-pneumatic transducers, valve positioners, indicators, controllers, or other direct-current devices. The level detector and control unit monitor and control liquid level range using a high-resolution, proportional output signal. This control operates under varying frequency power supplies or harsh process conditions, such as high pressures and temperatures. 

Malema Sensors added SumoFlo, a single-use flowmeter that measures flow rates from 50 gm/min up to 100 kg/min with accuracies within 1% of reading (5). Fabricated from gamma-sterilizable PEEK (polyether ether ketone), the device provides single-use flow measurement solutions for biopharmaceutical manufacturing applications including tangential and depth filtration, buffer dilution, cell cultures and cell harvesting, chromatography, and hygienic fluids with varying density or viscosity. Calibration parameters for each sensor are stored on a radiation-tolerant memory chip allowing the sensors to be interchanged with other SumoFlo electronics transmitter without affecting measurement accuracy. 

SupplyCare 3.0 from Endress+Hauser is an update to its Industrial Internet of Things (IIoT) application for tank inventory management (6). The system provides an overview of levels and product inventory in tanks and silos worldwide. Features include hardware and software options allowing level, flow, and pressure data to be displayed at a desk or handheld device, as well as inventory tools. The system uses Connect Sensor FXA30, a battery-powered cellular gateway for remote monitoring of level, flow, and pressure instruments in locations where power is not available. IMS SXS70 Middleware enables the integration of accumulated data with enterprise resource planning or manufacturing execution systems. Hardware developments include Fieldgate FXA42, a gateway that acquires data from local-level flow and pressure instruments and sends it to the local control system, transmitting the data via an integrated web server. 

Siemens’s Sitrans FS230, a digital ultrasonic flow system, consists of the Sitrans FST030 transmitter and Sitrans FSS200 clamp-on sensors (7). The system includes a digital sensor link that digitizes the signal at the earliest stage of measurement to optimize the signal-to-noise ratio. Because of the system’s 100 Hz data update rate and integrated algorithm, the transmitter detects small flow changes for rate accuracy of 0.5 to 1% and zero-point stability. The flow system’s patented pipe configuration menu allows the user to select various upstream pipe anomalies and automatically adjusts for flow profile disorders stemming from unfavorable upstream conditions. Other features include comprehensive diagnostics, mounting hardware, built-in startup wizards, and a customizable human-machine interface. Support tools provide direct access to all operational and functional data, certificates, and audit trails. Comprehensive diagnostics facilitate preventative maintenance. 

Semi-automatic powder handling technology

The JetBreaker system from ILC Dover is a semi-automatic powder handling system that deaggregates powdered media and buffer powders so that they can be better mixed in solution. Powders such as sodium chloride and ammonium sulfide may require delumping before dispensing into process liquids. According to the company, if the aggregates are not fine enough, they can damage process valves and equipment (8). Tests performed by the company found that the system produced homogenous powder while flowing through a feed hopper into the company’s jet venturi mixing systemat 1250 kg/h. 

References

1. Telstar, “Telstar to Introduce to the US Market a New Loading/Unloading Solution for Pharmaceutical Freeze-Drying Processes Driven by a Contact-Free Magnetic Propulsion System,” Press Release, February 24, 2017.
2. Telstar, “Telstar Integrates New Soft Sensor Technology to Monitor the Global Batch Product Temperature During Primary Drying in GMP Industrial Freeze-Dryers,” Press Release, July 4, 2017. 
3. Syrris, “Syrris to launch Titan Continuous Processing Scale-up System at InformEX,” Press Release, April 9, 2017.
4. Dynatrol, “GP Proportional Level Output Detector,” Press Release, May 11, 2017.
5. Malema Sensors, “Single-use, Gamma-Sterilizable Flowmeters for Bio-pharmaceutical Applications,” Press Release, May 10, 2017.
6. Endress+Hauser, “Endress+Hauser Releases SupplyCare 3.0 Tank Inventory Management Software,” Press Release, February 23, 2017.
7. Siemens, “Digital Ultrasonic Flow System with High Accuracy and Noise Immunity,” Press Release, April 24, 2017.
8. ILC Dover, “ILC Dover’s JetBreaker System Allows Rapid Mixing of Large Quantities of Pharmaceutical Powders,” Press Release, July 11, 2017.

Article Details

Pharmaceutical Technology
Supplement: APIs, Excipients, & Manufacturing 2017
Vol. 41, No. 9
September 2017
Pages: s39-s40

Citation

When referring to this article, please cite it as A. Lowry, " New Technologies Optimize API and Drug Product Manufacturing," Pharmaceutical Technology APIs, Excipients, & Manufacturing 2017 Supplement (September 2017).