Q. My application involves a peristaltic pump with silicone tubing running through it and a different, heat-sealable tubing material before and after the pump section. Recently, an operator installed the wrong section of tubing in a pump, resulting in lost API, equipment replacement, and hours of extra work. How can we avoid this kind of mix-up in the future?

A. One solution is to label different tubing sections for their intended use. Another approach is to use one tubing material, namely a thermoplastic elastomer (TPE), for the entire line. TPE is often used before and after the pump section where sealability is needed. TPE properties vary depending on the formulation and the process used to make the polymer, and in the past some formulations could not be used inside the pump. Today, however, there are versions of TPE that work very well in peristaltic pumps and can be used for the entire line.  

A possible concern is using steam sterilization with TPE because steam tends to deform tubing.  Some steam cycles can be used as long as they have a lower temperature and time exposure cycle and care is taken in positioning the tubing in the autoclave. A user who intends to sterilize with steam should validate their sterilization cycle with the intended use of a TPE tubing. Gamma radiation sterilization poses no problems with either silicone or TPE.

Using a single tubing eliminates fitting connections and tie wraps, along with their possible leaks and entrapment issues. Having a single material also simplifies the overall design, reduces inventory expenses, shortens assembly time and labor, and eliminates the possibility of installing the wrong tubing section in the pump.

—John Stover, product technical director, New Age Industries.

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Articles

Troubleshooting

My application uses a peristaltic pump with silicone tubing running through it and a different, heat-sealable tubing material before and after the pump section. Recently, an operator installed the wrong section of tubing in a pump, resulting in lost API, equipment replacement, and hours of extra work. How can we avoid this kind of mix-up in the future?

Working with Tubing for Peristaltic Pumps

Single-use bioreactor is designed for process development or pilot-scale cell culture


 EMD Millipore’s Mobius CellReady 50-L single-use, stirred tank bioreactor is designed for process development and pilot-scale mammalian cell culture. The rigid base and top panel design of the bioreactor process container enables simple, reliable, and robust one-way installation. Mobius SensorReady technology allows the user to configure process monitoring at the point of use and enables integration of new sensor technologies. The system is available as a turnkey solution complete with Finesse automation or as modules that can be integrated with the customer’s platform of choice. 

Meissner Filtration Products
 Containers support disposable biocontainer assemblies

Meissner Filtration Products’ QuaDrum containers for Meissner’s TepoFlex 3D biocontainer assemblies have a square design rather than the industry standard cylindrical design.  The design makes efficient use of floor space, and can be used with a stainless steel dolly for intra-facility transport. The reusable, polyethylene containers are chemically resistant and can be sanitized. Slotted lids offer access to tubing and filters or solid lids completely cover the assembly.

PharmTech's monthly newsletter, Equipment and Processing Report, reviews the Editor's Picks for the June 2012 edition from EMD Millipore and Meissner Filtration Products.

June 2012 Editor's Picks: Products from EMD Millipore and Meissner Filtration Products

Single-use systems offer clear benefits to biopharmaceutical manufacturing that include increased flexibility, reduced contamination, and time and cost savings. “A few years back, the value of single-use versus reusable was far from clear to end-users, but, in almost every case, those days are behind us now. A wealth of cost comparison data published by end-users, vendors, and industry organizations have demonstrated that, in the vast majority of situations, the single-use approach is more cost-effective,” says Richard Bhella, product manager at ATMI LifeSciences.

Cost analysis software programs can be useful in quantifying cost savings for particular applications and specific process conditions. Case studies using a cost-analysis program (BioSolve, Biopharm Services) found significant cost savings, particularly in reduced water use (1, 2). The Parenteral Drug Association will be publishing a technical report this fall that gives a primer on the economic factors of implementing single-use systems. 

Single-use systems have been finding commercial use in new capacity, new applications, or developmental–scale applications. In green-field sites, where the facility is being built from the ground up without the burden of previous process equipment decisions, the value of single-use-lower capital investment, faster startup and greater process flexibility-is clear, says Bhella. It is more difficult, however, to justify replacing existing commercial stainless-steel capacity.

Applications where single-use is seen as taking hold include routine mixing, such as buffer and media preparation, and liquid and powder storage/handling. “In these applications, the time saved simply from not having to clean the stainless-steel mixers is a huge throughput multiplier,” notes Bhella. Bioreactor applications have been slower to grow, probably due to excess capacity with existing equipment. One emerging single-use bioreactor segment is cell therapy, in which single-use technology makes manufacturing small batches of personalized medicines feasible, says Bhella.

Hybrid systems that combine multi-use, stainless-steel product-contact sections with disposable product-contact sections are often used. Hybrid systems reduce capital investment and move costs from fixed, up-front costs to activity-based costs (i.e., consumables) that are spent at the time of manufacture, notes Andrew Sinclair, president of BioPharm Services, in an analysis of hybrid systems in a monoclonal antibody manufacturing case (3).

 annual reader survey of biopharmaceutical manufacturers, 66% of respondents in both 2011 and 2012 reported that they use hybrid systems (4).Use of completely disposable systems is slowly rising however, with 12% of respondents in 2012 compared to 8% in 2011 saying that they used all-disposable systems.

E. Ayturk, presentation at Interphex (New York City, 2012). 

A. Ritter, “Bioprocessing & Sterile Mfg.” supplement to 

Production Lines

Time- and cost-savings benefits help drive increased use of single-use, disposable systems in biopharmaceutical manufacturing.

Finding Value in Single-use Systems

There are various theories about how to scale up a solid dosage coating operation in a pan coater. This article provides a basic process understanding and scale-up theory based on first principles. 

The coating process shown in Figure 1 has multiple, simultaneous, ongoing exchange processes. The first is a heat exchange between the inlet process air and the coater metal body, spray droplets, and tablets. The second is a mass exchange between the material sprayed and the inlet air stream, tablets, and coating pan.

There are certain losses (e.g., heat loss to the metal body and the environment), however, that cannot be characterized easily. An approximate mass and energy balance for the coating process in an equilibrium state can be calculated as shown in Equations 1–3, where 

The mass balance for the solvent is shown in Equation 2:

The mass balance for the solids sprayed is shown in Equation 3:

As with any theoretical analysis, there are assumptions built into the model described above. For example: 

•Leftover material in lines are not considered. 

•Heat loss to equipment body and environment are not considered. 

•Any unrecoverable mass loss in the process is not accounted for.

This model can be used to calculate process efficiency and efficiency of the inlet air heat capacity.  Efficiency of coating will generally improve as the process is scaled up because the bed depth will be increased, thus increasing the heat exchange between the process air and the tablets.

Various articles on scale-up principles have been published (1–3). The following basic scale-up principles can be applied easily in practice.

 Batch size scale-up is largely dependent on the pan size. As a general rule, the bed depth in proportion to the pan depth should be kept constant. This proportion will help to achieve consistent tablet flow in the scale-up batch, assuming the pans have similar dimensions. However, the technique can also be useful even if the pans are not geometrically similar.

 RPM scale-up is based on the industry’s accepted principle of using the linear distance travelled by tablets in the pan per unit time as constant and can be applied to obtain similar dynamic conditions during scale-up. The linear distance is calculated as πD, where D is the pan diameter.

  Pan RPM can be calculated using Equation 4.

 Air flow is frequently limited by the particular equipment and/or blowers installed on the system. It is important—particularly for functional coatings—to keep the drying kinetics constant as the process is scaled up. This action can be accomplished in accordance with the spray rate scale-up presented below.

 Spray rate scale-up needs to be in step with air flow scale-up. The coordination should be based on more than the batch size increase because equipment that provides a five-fold batch size increase may only allow a two-fold increase in process air. As a general rule, product temperature should be constant across scales. It is often possible to increase the temperature to allow for higher spray rate during scale-up, but this increase depends on the sensitivity of the coating material, or polymer, and its film-forming properties.

The general principles described above underpin the tablet coating process and can support successful scale-up.

2. S.C. Porter, "Scale-up of Film Coating," 

, M. Levin, Ed., (Marcel Dekker Inc, New York, USA, 2000), pp. 259–310.

Scaleup and Design of Industrial Mixing Processes

Abhishek Kathuria is manager of formulations at J&J Consumer Healthcare, Fort Washington, PA.

In the Mixer

An understanding of the pan-coating process based on first principles can support successful scale up.

Equipment and Processing Report-06-20-2012

Working with Tubing for Peristaltic Pumps

June 2012 Editor's Picks: Products from EMD Millipore and Meissner Filtration Products

Finding Value in Single-use Systems

A Practical Guide to Pan Coating and Scale-Up