Frequently Asked Questions

• How is water temperature regulated?

• How are supplements and samples taken from the re-circulation loop?

• How are the filters used in the system?

• What is the skid footprint?

• How does the "new" mixing system compare with tank and impeller?

• What is the typical batch cycle time or process turnaround time?

• What is the re-circulation time of media /reagent within the tank?

• Can I use media bags other than HyClone’s?

• How are the liners disposed?

• How much do the liners with mixers weigh?

• Are the bags FDA approved?

• Are the disposable bags validatable?

• What options are available for operating as a "closed" system?

How is water temperature regulated?

The process fluid is tempered using a closed loop glycol re-circulation system capable of maintaining an environment from 10 to 40 C ±1C with Steam and Chilled Glycol. We introduce WFI or RO (USP) water through a sanitary heat exchanger that is also jacketed with tempered Glycol to formulate the batch at the correct temperature. 

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How are supplements and samples taken from the re-circulation loop?

Samples (up to 100ml) are drawn from the re-circulation loop using a large plastic syringe and a Luer-lock fitting. Larger samples are taken on the positive pressure size (downstream of the peristaltic pump) with a disposable bag and pinch clamp arrangement. Liquid Supplement additions, pH adjustments and Sera are drawn into the re-circulation loop via the re-circulation pump and a sequence of pinch clamps on the tube set. Automatic pinch valves with disposable cores are available if desired. 

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How are the filters used in the system?

The disposable process fluid filters are used in parallel banks of descending micron size and hosed to the final 0.1-micron filter. Only one bank is used at a time and we monitor the pressure differential across the entire bank to signal when we need to switch banks and change the loaded filter. We can accommodate up to five (5) (Depends on which filter manufacturer) pre filters per bank, each being single round high (10”, 20” or 30”), and can adapt to different manufacturers. All of the filters are tri-clamped together and tube sets deliver the process fluid to and from the bank. Pinch clamps provide flow direction and control. Additionally, we use filters on DI water feed when making process water batches, all water is filtered into the tank, 0.2-micron air filters to inflate the liner and 0.2 micron filters to maintain a clean air purge on the head space during powder addition. 

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What is the skid footprint? 

A “complex” module with two liner holders - a 10,000 liter vessel and a 3,000 liter vessel is 8’-0” wide x 24’-0” long and 14-6” high. All of the process and utility systems are contained within the skid boundaries, including the agitator hydraulic drive, MCC, PLC, Tempered Glycol control loops, WFI sanitary heat exchanger and a 150Kg capacity 3-axis mechanical arm to load liners and dry powders. 

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How does the ‘new’ mixing system compare with tank and impeller?

Mixing trials have shown that the unique HyNetics™ agitation scheme is very efficient and powders go into solution very quickly. The high turbulence created by the interaction between the vessel shape and the disposable mixing unit geometry help “pull” materials into the fluid stream as they are metered into the BPC mixer vessel. Powders are not “dumped” and stirred as usually found with traditional mixing tank designs.

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What is the typical batch cycle time or process turnaround time?

Total batch time varies depending upon water draw rate and final fluid delivery, which could be bulk delivery, packaging, etc. Batch time also includes disposables staging. The 3,000-L bag and the 10,000-L bag each take about 10 minutes to properly load into the holding vessel. The 3,000-L bag takes about 9 minutes to inflate with filtered air to assist in final positioning, while the 10,000-L bag requires about 25 minutes. Both are inflated using air from the skid frame, which serves as the reservoir. Liquid fill on HyClone’s in-house system is about 1hr 40 mins for the 3,000-L bag and 3 hrs 34 mins for the 10,000-L bag. The limiting factor is the WFI flow out of the heat exchanger, which flows at a rate of 30-35 lpm on our system.

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What is the re-circulation time of media/reagent within the tank?

The disposable mixing unit reciprocates up to 2 Hz and the mixing rate can be adjusted from 0 to 2 Hz (mild to aggressive agitation depending on process requirements and product shear sensitivity). This results in fluid velocity rates varying within the tank. The peristaltic pump runs at a rate of 30 LPM @ 30 PSIG to the filter bank. Higher flow rates at lower pressures are possible. Recirculation within the mixing cycle is not necessary since we have an extremely efficient agitation motion. Re-circulation is used to support sampling and liquid supplement additions.

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Can I use media bags other than HyClone’s®?

The system is custom engineered to use HyNetics™ disposable BPC products as an integrated process. The BPC liner is specifically matched to the vessel and agitator drive. Our powder and liquid addition bags as well as the tube sets are designed to pump process fluid to any type of discharge container whether it is a disposable bag, canister, tank, reactor, or HPLC column. We recommend using the HyClone films and tube sets since all contact surfaces are certified ADCF. The unit is only compatible with the HyNetics™ mixing bag, which is the main container for formulation and contains the disposable mixing unit. We also have a new product, which allows filling of bags in a “gray space” using electron beams to irradiate the connector surfaces.

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How are the liners disposed?

This is up to the end-users. The films are predominantly polyethylene, a very easy resin to recycle and one that is very clean to incinerate (burns to H2O and CO2) and burns quite hot making it a good fuel. It is also quite inert which is ideal for modern landfill technology. As an alternative to disposing CIP reagents, these disposables offer a “green” alternative to disposal sensitivity.

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How much do the liners with mixers weigh?

The 3,000-L liner with mixer weighs 27 lbs out of the box, and 50 lbs in its box. The 10,000-L liner with mixer weighs 33 lbs out and 55 lbs in the box.

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Are the bags FDA approved?

The FDA does not officially approve a product such as disposable bags or film. However, this film has been USP Class VI tested and it passed. It was co-developed with a major medical device company.

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Are the disposable bags validatable?

Yes. HyClone customers have done their own validations and HyClone has done its own as well. Different customers may want to validate different aspects, such as seam strength, burst strength, puncture strength, port seals, etc. HyClone can provide a data sheet on the film if requested.

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What options are available for operating as a "closed" system?

Please refer to our Guideline which describes the various options that are available to make aseptic or sterile connections in single-use components in general, and specifically, in the operation of a HyNetics™ system. In addition to the information contained in this Guideline, HyNetics™ can provide specific recommendations for your particular application.

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