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Equipment and product innovations improve pharmaceutical manufacturing tasks.
Being knowledgeable of the most advanced equipment and technologies available for manufacturing is essential for tackling and preventing production issues.
Over the past several months, equipment innovations have been introduced and updated to enhance pharmaceutical manufacturing operations. The following is a sampling of such products and equipment options.
Sartorius Stedim Biotech’s new automated parallel bioreactor system, ambr250, is a high-throughput bioreactor system suited for rapid cell-culture perfusion culture process development to increase therapeutic antibodies production (1). The system combines 12 or 24 single-use perfusion mini bioreactors with associated single-use perfusion components, all controlled by one automated workstation, as stated by the company. The mini bioreactors have a working volume range of 100-250 mL.
According to Sartorius Stedim, the combination of this multi-parallel processing capacity and fully single-use perfusion vessel allows for more perfusion culture experiments in less time and cost compared to traditional perfusion-enabled benchtop bioreactors. The system is suitable for a range of hollow fiber perfusion applications, which allows for design-of-experiments studies for high cell density process development in a quality-by-design approach.
The system, which is a collaborative effort between Sartorius Stedim and other biopharma companies, uses a perfusion bioreactor assembly based on the company’s branded bioreactor design.
Components such as high efficiency spargers, perfusion pump chambers, and an industry-standard hollow fibre for cell retention filter enable intensified cell culture processing. The system’s fully assembled and irradiated perfusion bioreactors come with all necessary components, including single-use sensors to continuously monitor pressure at both the culture fluid inlet and permeate outlet, which enables online monitoring of transmembrane pressure and standard parameters such as pH and dissolved oxygen.
“Transitioning from fed-batch to perfusion culture offers the potential to reduce capital intensive risk by using 1-2000-L single-use bioreactors instead of 10,000-L production volumes in stainless steel,” said Dr. Barney Zoro, ambr product manager at Sartorius Stedim Biotech, in a company press release.“[A]mbr 250ht perfusion is a predictive process development tool that could lower the cost of goods of antibody production, as well as significantly shortening development timelines.”
Watson-Marlow Fluid Technology Group (WMFTG) has added Q Clamp, a new sanitary tri-clamp connection for single-use fluid path applications, to its BioPure brand (2). The clamp can provide a secure connection in less than 12 seconds, according to the company.
The clamp does not require any tools for application or removal and can be closed using one hand. The company reports that a double-sided ratchet ensures that the lightweight clamp remains shut in the event that one side should fail.
The clamp comes with a tamper-evident identification technology solution for tri-clamp connections, which can also be used for identification through eight color options, allowing procedures to specify relevant areas of the process, according to WMFTG. Application of this solution is possible either before or after the clamp is assembled.
The connection tri-clamp, which is backed by a validation pack for non-wetted components, is manufactured and packed in an International Organization for Standardization (ISO), Class-7 cleanroom and meets current ISO and United States Pharmacopeia <87> and <88> industry requirements. The company also confirms that the clamp has been evaluated for extractables using a single solvent approach.
The MagMixer MBE Series from SPX Flow is a hygienic magnetic mixer that meets current operational standards and regulatory compliance and is suitable for low-viscosity blending, dissolving solids, and solid suspension in sterile applications (3).
The mixer has bottom-mounted magnetic agitators, is engineered using computational fluid dynamics, and uses Lightnin A281 3-blade hybrid axial/radial impellers in an open construction that facilitates improved cleaning and sterilization. Magnetic impellers remove the need for shaft and seals, which significantly reduces the risk of leakage or microbial contamination, according to the company. SPX Flow reports that in addition to optimizing product flow, the impellers also produce high levels of torque capacity in a compact form.
Robust ceramic bearings reduce the risk of breakage, are product-lubricated, and enhance mixer stability, reliability, and performance, as stated by the company. The bearings can be easily replaced on-site with no need for a spare impeller.
The unit is controlled by a variable frequency drive and covers a power range from 0.09 to 7.5 kW (0.12-10Hp) with operating speeds between 200-1000 rpm.According to SPX Flow, “magnetic lifting of the impeller reduces the load on the surface of the bearings and enables the mixer to continue to run until the mixing vessel is completely empty, improving formulation mixing.” Unit range options include a variety of bearings, O-rings, drive, and body materials.
Munson Machinery’s rotary batch mixer with a integral lump breaker provides inline de-agglomeration of compacted bulk materials before gently blending batches uniformly in one to three minutes regardless of disparities in the bulk densities, particle sizes, or flow characteristics of batch ingredients, according to the company (4).Material entering the new De-Clumper model RDC-1515-SS is de-lumped by dual rotors with three-point, single-piece, stainless steel breaking heads rotating with minimum clearance inside a curved, perforated bed screen. On-size material passes through bed screen apertures, which range from 1/16 to 2½ in. (25-64 mm) in diameter, immediately before entering the stationary inlet of the mixer.
The mixer has a useable batch capacity of 50 cu ft (1.42 m³) and weight capacity of 4000 lbs (1814 kg) and is equally effective in blending of batches from 100% to as low as 5% of rated capacity, as stated by Munson. As the mixer’s horizontal drum rotates, proprietary mixing flights tumble, turn, cut, and fold the material, imparting minimal energy to the batch, minimizing or eliminating degradation.
Munson states that inline stacking of the system, when above the stationary inlet of the model 700-TH-50-SS mixer, minimizes headroom requirements while eliminating the need for flexible connections or hard piping between the units. Synchronized shafts rotate at 120 rpm to prevent heating and degrading of the product.
The internal flights lift and direct the entire batch into the stationary discharge spout for evacuation without leaving residue of material behind, eliminating waste and improving product quality while facilitating rapid, thorough cleaning.
A heating, ventilation, and air conditioning (HVAC) control system from Telstar automatically controls the particle concentration level in cleanroom air to maintain the required environment, depending on the cleanroom grade classification and activity (5).
The HVAC control system is connected to a particle counter and air-handling unit, and it adjusts the number of air changes to reach the maximum level of particles permitted in the room according to its GMP classification, following the regulations stated in European Union GMP Annex 1 and ISO Standard 16644-1.
Depending on the room, the system can reduce energy consumption by more than 40%, according to the company. The system maintains pressure, temperature, and humidity variables under stable conditions, and provides steady air changes, without oscillations.
1. Sartorius Stedim Biotech, “Sartorius Stedim Biotech Launches New Ambr 250 High Throughput Bioreactor System for Perfusion Culture,” Press Release, March 14, 2018.
2. Watson-Marlow Fluid Technology Group, “Biopure Q-Clamp is Compatible with a Wide Range of Connector Geometries,” Press Release, Feb. 8, 2018.
3. SPX Flow, “New Hygienic Magnetic Mixer Designed for Exceptional Performance and Reliability,” Press Release, March 5, 2018.
4. Munson Machinery, “Rotary Batch Mixer with Integral Lump Breaker,” Press Release, Dec. 22, 2017.
5. Telsar, “Telstar Designs an Innovative HVAC Control System that Provides Automatic Regulation in Clean Rooms,” Press Release, Jan. 25, 2018.
Vol. 42, No. 4
When referring to this article, please cite it as A. Lowry, “New and Updated Equipment Streamline Manufacturing Operations,” Pharmaceutical Technology 42 (4) 2018.