• Traceability
• Integrity
• Hidden Costs
• Facility Design
• Total Solution
• Vendor Partnership

To read more, I have attached a copy of the paper for your convenience. (Download 2.4MB file and view with MS Powerpoint for your own interest. Please do not download copy and reuse without permission).

That only leaves Millipore and Sartorius as the larger vendor suppliers without a full bore flow through connector. But then again how many connectors does the bioprocess world need?

With this proliferation of connector options, increasingly the hapless end user is left with the dilema of interconnectivity between options or needing to choose custom bag and tubing configurations. Does any one want to engineer and license a universal connector?

My personal list of preferences include considerations for:

• Cost
• Ergonomics (Weight, is it translucent, can it be easily assembled by a gowned operator?)
• Materials of construction
• Sealing and aseptic reliability

Other lesser issues are hold up volume within the connector itself and drainability - can I get everything out! Everything else being equal, I also prefer a translucent unit over an opaque connector - being able to see what is happening within the connection is helpful.

The above are all pretty straightforward. However, one element that is often important is the actual backpressure at process flowrate through the connector. (That is, the Kv of the valve). Millipore’s Lynx products and Colder’s Steam-Thru II both have significant backpressure for equivalent flowrates compared to Pall’s Kleenpak and Bioquate’s DAC. The reason is quite simple since both Colder and Millipore force the process fluid through a fairly tortuous path around a movable plunger element. Both Pall’s Kleenpak and Bioquate’s DAC use a method of actuation that involves the removing of a film that leaves the full internal bore of the connector available for flow and therefore result in lower backpressure and associated shear.

In March 2007, Pall challenged Bioquate for potentially infringing Kleenpak’s design. At the time of writing, this dispute is unresolved.

Interphex2007 was quiet a disappointment for me. An interesting snippet was trying to reason why GE has acquired Wavebiotech. It is probably not wise to go into this speculation on-line as I prefer to stick to factual or innovative material. However, the continual consolidation of the supply industry IMO does not bode well for innovation or speed of new product introduction. However - I would like to be proven wrong.

George Adams (previous affiliation in Millipore disclosed), showed me the latest RFI tracking capability available on Millipore viral filter capsules. Although RFI has been implemented on pure water systems from Millipore for a while - this is the first RFI application for having embedded devices in bioprocess devices. It will be very interesting to see how this is taken up by the industry. IMO Millipore still “owns” integrity testing of sterile filters and therefore have a good starting position for this product. I am very interested to see how end user adopt the usability of using a reader, 21 CFR Part 11 issues etc. It would be an interesting bioprocessing world, where the integrity testing and all manufacturing information travelled in with the disposable device and could be electronically scanned to uniquely identify all manufacturing elements that were in contact with the bioprocess batch. But that waits for a later date.

Today, Xcellerex had the most complete offering for CMO disposable innovation. Pall and Millipore - in my opinion again - still seem to be deciding on their positioning. No one really has taken a decisive lead marketing position. Thermo has consumed Hyclone and TC Tech, I am also disappointed by this ;-( . As you can probably tell - the author is pretty adamant that consolidation is not necessarily going to help the cause of disposable manufacturing. At least not until one of the larger acquirers actually takes a pioneering position and diverts both product and marketing investment to do other than try to follow the tide and milk the trend.

But good luck to all my contacts, who are now part of a larger strategic acquisition. Change can be good!

Both these exhibitions are quite expensive for exhibitors and squeeze out the little guy or niche player. However, I did bump into a couple of contacts, one was an ex-millipore contact who has started Pendotech. I hope to have a chance to review their ideas at a later stage.

Judging by the overall attendance, crowd control, and activity - I don’t see any change in the level of industry activity. At Expo2007 in particular, disposable technolgies continued to take a front position in bioprocessing technology. So the state of the union still seems healthy.

Over the next couple of weeks - I will talk about two topics that I was most interested in from these shows:

• leachables
• disposable chromatography

In this post, let’s talk about the current state of available sensors. In a separate post, I will talk in greater depth at a later point about flowrate determination and about particle size determination and turbidity. However lets discuss the other sensors….

An ideal functional specification for our preferred sensor would be that it is light weight, has NIST traceable calibration, is linear and highly accurate, materials are all inert and documented, that the sensor comes as part of a pre-sterilized drop in place tubing assembly, and is sufficiently low cost that it can realistically be single use.

In an ideal world, we might also want the instrument to talk invisibly to us either via wireless technology or at least a clear easy to read display. Cables are both a trip hazard to the user and generally clutter the process area. Despite the inherent containment provided by the bag set to the fluid – most people still prefer to operate in true or near clean room environments. Again cables are bad news for a number of reasons including particle shedding. An ideal would be a 100% sealed and stand alone, battery driven datalogger, using ASIC or other low power digital processors.

In a real world, many sensors that are used are not disposable but form part of the framework that gets reused for each new bag set. For example proximity sensors (ultra-sonic, optical or capacitance) for determining fluid level are often mounted on the frame and register fluid level within a tubing set of bag

The actual sensor business end for at least temperature, pressure and conductivity need not be very expensive – either. Small micro-strain gauges and the associated Wheatstone bridge and printed circuit boards can have very low manufacturing components costs. However, to date no manufacturer has either had the sales volume or desire to provide a really low cost component.

In my opinion, for the most part Bag manufacturers are still in the learning stages about instrumentation. One supplier (an equipment verses bag supplier), who is perhaps the furthest ahead in this direction, is SciLog. I have used a number of their disposable, pre-calibrated sensors for conductivity, temperature, and pressure and can confirm they work. Typically we are not seeking very high accuracy and SciLog products are a reasonable flow through option. They even provide a wide range of connection options. However, at least for now you are still on your own when it comes to coupling your tubing set to the sensor component. Here is a quote from their published marketing:

For truly disposable sensors, bioprocessors should look into products from Scilog (www.scilog.com), which introduced a line of single-use disposable fluid-path products pre-fitted with. Sensors for additional process parameters are in development.
SciLog also holds several patents on single-use manifolds for automated, aseptic liquid transfer for liquid-intensive separates such as filtration, tangential flow filtration, ultrafiltration, reverse osmosis, sterile dispensing, bioreactor feeding, and chromatography.
These are smart sensors, says product manager Julie Schick. That means the devices contain embedded memory in which they store identification numbers, lot numbers, and calibration data. The sensor transmits this information to the SciLog monitor, which feeds back to the automated equipment and data collectors.

But does the list price of the average disposable assembly cause you concern? Does $200 for a 50l plastic bag sound expensive? The biopharmaceutical industry is an exciting environment as it is rarely consumable costs that are a go or no go criteria. Or as written up in a more scholarly article by Mike Hoare, Nigel Titchener-Hooker et al :

"…..the capital investment required for a disposables-based option is substantially reduced at less than 60% of that for a conventional option. The disposables-based running costs were evaluated as being 70% higher than those of the conventional equivalent. Despite this higher value, the net present value (NPV) of the disposables-based plant is positive and within 25% of that for the conventional plant."

Although 25% is significant for many manufacturing industries, it is generally less significant for this industries where uncertainties and time to market are the primary drivers.

So the question remains unanswered - "What is a fair price?" I am really curious as to what others feel and think about this. I don’t expect that any bag or other disposable supplier will be about to suggest how they got to their number or disclose their market analysis on price sensitivity.

     "Cool!"

So it was a sad summers day when I was sat in a rather hot meeting room in a  discussion with a vendor about a custom disposable bag drooling over the latest widgets they had available, instead of the bagels which were rapidly going stale on the meeting room table.

On this occassion the issue was relatively small but as every journey starts with a first step. The small catalyst that started this ball rolling was simple enough. Well known bag supplier "A" made a bag, which as standard terminated in a male connector. Well known connector supplier B made a stainless connection which was only available as a male connector. Even I know that male to male connectors don’t get along too well at least not in a clean room. The solution they offered was a custom assembly with 6 or more likely 9 week leadtime.

The solution, I thought was to find a way to make suppliers and end users all talk with one another. Offering custom solutions to every minor issue is a million miles away from the ethos of ordering a disposable product on-line and having it arrive just in time to be used the following day.