In March this year, the European Patent Office issued its annual report for the previous year’s activity.
For the second successive year, the pharmaceutical and biotech categories were booming; in 2017 pharma recorded an 11.7% increase in the number of patents being filed; in 2018 the sectors repeated their previous double digit growth, with pharma attaining a 13.9% increase and biotech 12.1%.
In the UK specifically, the rise in pharma filings topped 20% while pumps, engines and turbines technology was close behind on 19%.
Where the pharmaceutical and biotech sectors are concerned, the number of blockbuster drugs falling out of patent is a factor in the flurry of activity. As for the flurry of pump applications, that must come down in part to their potential to provide a competitive edge in these and other sectors.
Talk to anybody in the pharmaceutical industry and two key concerns are guaranteed to come to the fore – process containment to prevent leakage to atmosphere and minimising the risk of product contamination
John Smiddy, European sales and technical support director, AESSEAL
The key challenges that determine their value in pharma and bio uses are of course hygiene, shear and precision.
Elsewhere in this issue, ABB global segment manager, pharmaceutical and life sciences, Gero Lustig, cites the need for greater product variety and shorter runs. Faster production changeovers are a consequence of this but increase the potential for contamination.
Shear rates and stress need to take account of the limitations of individual liquids and mixtures, while dosing and metering must ensure accurate and consistent product regardless of scale of production.
Given the commercial pressures coupled with the regulatory demands placed upon manufacturers, it is hardly surprising an attitude of risk aversion prevails. Yet in an era in which cost has become more of an issue, that attitude may need to alter.
John Smiddy, European sales and technical support director at AESSEAL [pictured], questions whether the industry is in danger of overlooking what is in its best interest.
Process containment and reducing the risk of product contamination are key requisites for pharmaceutical production equipment, he points out, and yet the industry is notoriously averse to change when it comes to the selection of mechanical seals and seal materials. Selection, he points out, is key to improving the reliability of rotating equipment, reducing process contamination risk and delivering savings.
“Talk to anybody in the pharmaceutical industry and two key concerns are guaranteed to come to the fore – process containment to prevent leakage to atmosphere and minimising the risk of product contamination,” states Smiddy.
“But when it comes to considering the design and composition of the sealing components on that equipment, it seems perfectly content to accept outdated and inefficient technology over advanced, industry-compliant modern sealing solutions which are proven to eliminate leakage and reduce the risk of product contamination.”
Part of this reluctance, suggests Smiddy, has little to do with the merits of the product but rather more with simple inertia or reluctance to tackle the administrative issues; amending change and recipe controls is deemed too onerous, while even senior engineers may face a bureaucratic nightmare getting signoffs.
Additionally, mechanical seals can be easily ignored, while outdated mechanical seals and support systems may be specified to keep a lid on costs. Thus, a pharmaceutical plant could have a critical asset fitted with original equipment manufacturer sealing technology and materials long out of date.
“A typical example would be a single balance seal with seal face materials made from poor quality carbons, ceramics or Ni-resist materials, and PTFE wedges as the primary sealing element,” explains Smiddy.
“PTFE wedges are fast-wearing and unreliable. They seal directly to the shaft, fretting against it and causing damage which allows process to leak into the barrier fluid that keeps seal faces lubricated and cool. The risk of contamination is in-built. Seal failure is swift and inevitable.”
GEMU takes a similar view on the use of PTFE as a lining material for its metal butterfly valves, used in pharmaceutical and other applications and favours instead PFA and TFM linings.
PFA is melt processible rather than being isostatically compression moulded from sintered chips, allowing it to be precisely moulded, says the company. TFM incorporates a PerflouroPropyl Vinyl Ether (PPVE) modifier to the PTFE which reduces cold flow by a factor of three, has a firmer polymer structure, is less permeable to gas and chemicals, weldable and smoother surfaced.
The GEMU 490 series of lined metal butterfly valves are available with body liners in either material; plastic injection moulding ensures precise locking to the valve body and corrosion resistance. Added to this, a four-fold shaft system of main, radial, safety and additional seals prevents dangerous leaks.
For AESSEAL’s Smiddy, traditional seal technology favoured on many pharmaceutical lines is all too often a barrier to certainty.
Wet seal solutions are pressurised using barrier fluid but if too thick and viscous will risk tearing the seal faces and increasing leakage. There’s also the issue of barrier fluid temperature – its common temperature of 30-40°C is “an ideal breeding ground for bacteria”, he warns.
Change is good
Finally, while there’s a need to change the fluid every day, in fact, this may not occur even monthly.
On balance, Smiddy advocates dry gas contacting seals as the most reliable across the greatest range of applications, also the first choice for the major pharmaceutical firms, he maintains.
Opting for gas rather than liquid barriers means a requirement of less than 5% humidity, removing the need for humidifiers and the threat of wet gas contamination.
However, material selection is still an issue, with highly tested FDA-compliant carbon such as Schunk recommended. Be prepared to exercise caution when dealing with OEMs, advises Smiddy. “Companies will happily spend anything from £10,000 to £50,000 on a dry gas seal provided by OEMs, which often comes without a display panel. If you bought a new car and there was no display panel on the dashboard, would you drive it?
”While sealing technology has advanced significantly, its cost hasn’t. And the improvement in reliability has been huge – increasing mean time between failures from one year to five in many cases.”
Price, that bugbear of the economically hard-pressed process company, is so often the stumbling block for the smaller to medium firm seeking to innovate and achieve sustainable long-term growth.
Harnessing the benefits of automation and Industry 4.0 for pumping systems is an objective made difficult to achieve for many because of the investment level needed for product purchase and training.
Disposable equipment adds a lot flexibility in both the upstream and downstream processes. It is quicker to assemble and requires less investment, given there is no requirement for cleaning and sanitisation
Gero Lustig, global segment manager, pharmaceutical and life sciences, ABB
If single-use technology implies more not less waste, it can reduce cleaning, personnel and validation cost, contamination and water/chemicals consumption.
ABB’s Gero Lustig is clear about the benefits of such equipment as part of a wider company strategy to develop a more agile manufacturing response to changing demands in the pharmaceuticals sector.
“Disposable equipment adds a lot flexibility in both the upstream and downstream processes. It is quicker to assemble and requires less investment, given there is no requirement for cleaning and sanitisation,” he explains.
“This saves on time, enables faster product changeover procedures and reduces work hours.”
Both peristaltic and diaphragm pumps can be well-suited to single-use, examples being Watson-Marlow’s Quantum with ReNu SU cartridge and PSG Dover’s Quattroflow diaphragm pump used in biopharma research.
Combining disposable equipment with automated processes ensures that manufacturing benefits will accrue still more, says Lustig.
“However, the production can be made even more agile when modular automation concepts are combined with disposable systems, joining different modules to each other and orchestrating the processing line and steps.
“As a result, set up time of the production line from an automation perspective can be cut down tremendously in some cases, enabling factories to get online up to one year earlier and operators to begin making a return of investment approximately 25% faster,” adds Lustig.
Valve technology has a part to play in keeping syringes clean and efficient
Satron Instruments’ sales and service manager Ken Roberts highlights how specialist manufacturers have focused on producing devices to improve the potentially hazardous, difficult and time-consuming chore of recovering and getting samples to the lab.
“High pressures and temperatures, together with difficult to handle fluids that can also be potentially dangerous, can be an accident waiting to happen for the individual charged with obtaining said sample.”
Straightforward as it seems, the procedure involves multiple small steps where failure could compromise the end result: reaching the access point, capturing what flows out without spillage or contamination; then ensuring a correct quantity and a representative sample is collected, labelling and transporting to the lab; and doing so safely.
“The easiest hygienic sampling uses a syringe pulling the sample through a hollow needle pushed through a rubber septum. No messing around with turning handles to clean the sample valve and another to start the sample flow,” advises Roberts.
But when the septum has been used many times, it needs to be replaced and this requires a shutdown. Satron’s PASVE S product solves this by putting the septum in a little hygienic valve to permit safe, clean, fast and simple replacement while the process is underway, says the company.