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September 15, 2017 (Vol. 37, No. 16)

To Surge or Not to Surge?

Experts Discuss Inclusion of a Surge Tank in an End-to-End Continuous Biomanufacturing Train

  • There have been very few projected models of best practice for end-to-end (i.e., truly or fully) continuous biomanufacturing. Based on some of the patents filed and/or granted for a totally continuous model, a notable difference between models is the use of a surge tank between upstream and downstream operations. Some experts argue if you are using a surge tank, the model isn’t really continuous, while others argue the benefit of using these tanks, asserting they add safety to the process stream. Below are some expert perspectives on the matter.

  • GEN: How do surge tanks add safety to a fully continuous manufacturing line?

    Gerben Zijlstra (Sartorius Stedim Biotech): Basically, surge tanks allow short stops of the following unit operation, without the need for stopping or even terminating the entire process. These short stops may enable short maintenance activities, to resolve failure modes (e.g., exchanging blocked filters, exchanging pump tubing, exchanging reduced capacity resin), thereby substantially mitigating the risk of premature process termination, by small incidental failures.

    Michelle Najera (CMC Biologics): In an ideal case, all steps in a continuous manufacturing line process would operate at the same pace so that there is uninterrupted flow between steps. However, without surge tanks, the entire processing line would need to slow down or stop altogether if there was a pause or slow down for a single step. Surge tanks between each step increase the flexibility and robustness of a continuous manufacturing line by providing a temporal cushion between the linked steps. Additionally, a surge tank is often needed to maintain relatively low operating pressures. If all unit operations are connected without a break, the pressure rating for the upstream operations would likely be higher than equipment typically used in biomanufacturing.

    Gerard Gach (LEWA): [Surge tanks] would allow for individual unit operations to adjust to variations in productivity of other unit operations either up or downstream. Also, they might have some utility as draw points in monitoring product quality management. Engineered properly, a continuous production scheme should not need surge tanks.

    Andrew Zydney (Penn State University): Surge tanks can be a very appropriate way to handle process disruptions in a fully continuous manufacturing line. All processes/unit operations require some maintenance (e.g., replacement of membranes in a filter module). A properly designed surge tank would allow the rest of the process to continue to run while an operator replaced or cleaned the membranes. In addition, surge tanks can help manage fluctuations in flow rate and product concentrations. This is particularly important when using processes that operate in a cyclic fashion (e.g., multi-column chromatography systems), in which the product flow rate and concentration vary with time over the cycle. The surge tank can effectively ‘average out’ these variations, providing more effective operation of the subsequent downstream process.

    Dana Pentia (Repligen): In an ideal world, a surge tank will not be needed. ‘Ideal world’ implies that all the process steps are perfectly synchronized and controlled. However, if the process is not fully synchronized, controlled and understood, a surge tank is needed as a link between steps.

    Massimo Morbidelli (ETH Zürich): Surge tanks are mainly a safety measure to ensure that the product quality can be monitored between upstream and downstream and that in case of downstream problems, not the entire batch was lost. It also allows for the balancing out of any variations in feed titer and quality, so that the Protein A capture step can be run consistently with the same feed load, ensuring that the same yield and ratios of product to impurities are loaded. We have shown in a recent paper how the integration between these two units can operated so that any feed titer variation or Protein A capacity decrease can be offset, ensuring a consistent process.

    Karol Lacki (Avitide): A surge tank is not a unit operation that is introduced to improve product quality and, therefore, it does not affect product safety. Product safety is secured through a right choice, and subsequent careful design, of unit operations that assure the desired purity. On the other hand, a surge tank can improve process robustness. Surge tanks are added to a process sequence to reduce variation in the composition of the product stream and/or to allow for introduction of extra pumps if other pumps upstream are not powerful enough to deliver an uninterrupted flow through several unit operations (e.g., chromatography steps connected in series). However, if a chromatography step is operated in the bind-and-elute mode, the product stream composition changes during the elution stage and this variationin  the product concentration may have a negative effect on the performance of the subsequent unit operation. Usually it does not, but if it does, a surge tank can help eliminate this effect.

    In the case of chromatography steps operated in flow-through mode, a surge tank is not needed, unless a significant adjustment of the stream compositions (pH/salt) is needed. And even then, commercially available technologies for in-line adjustment of pH or conductivity can be used instead. Some could argue that surge/break-up tanks can be used as intermediate quarantine tanks as part of the process control strategy if a deviation occurs. From that perspective, it would probably be more advantageous to have standby tanks that are not part of a normal operation.

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