Patent cliffs, biosimilars, regulatory demands and counterfeiting are piling on the pressure but there’s no shortage of routes to greater efficiency, learns Brian Attwood.
Pharmaceuticals manufacturing is renowned for its ‘bull and bear’ periods. A company can be riding high for an extended time, buoyed up by the success of one or other patented product.
Then, overnight, it can find itself off the proverbial patent cliff when a flagship product goes off-patent.
“For decades, the cost of pharmaceutical manufacturing has been low, compared to the returns made on new patented prescription drugs,” explains Ian Shott, chairman of BPE. “However, that landscape is changing – not least due to the patent cliff of the last decade – and the cost of goods for major pharmaceuticals is increasingly under the spotlight.”
For Gero Lustig, global segment manager, Pharmaceutical and Life Sciences, at ABB Energy Industries there is at least a benefit in terms of driving innovation: “We are seeing large companies move away from blockbuster-style drugs and instead focus on developing more specialist drugs. Meanwhile, generic drug makers are taking full advantage of the patent cliffs expanding into new markets and territories.”
The landscape is changing – not least due to the patent cliff of the last decade – and the cost of goods for major pharmaceuticals is increasingly under the spotlight
Ian Shott, chairman, BPE
The development of biosimilars has added a further ingredient, he adds, citing Results Healthcare’s 2017 report of forecasts of 20% increases in development projects. While the market is still in its early stages and the regulatory process not yet solidified, it is expected that multi-billion pound savings can be achieved.
Less cost, more agility
Shott too sees a cost implication from such innovation, noting: “In order to grow their businesses, and against a backdrop of more strongly regulated developed markets and more cost sensitive developing markets, there’s a greater need to reduce costs.”
The growth in personalised medicine, meanwhile, creates niche demands that call for greater production flexibility, regulatory demands have become more complex and multifaceted. Biotech advances present competitive challenges as well as complementary services.
“Today’s pharma companies need to be more agile and scalable than ever,” cautions Lustig [pictured]. “Companies need to manufacture greater product varieties, with shorter production runs, partly driven by the demand for personalised medicines.
“Producing batch sizes of a few litres in a commercially viable environment is the challenge. End-to-end within less than a week is the mantra of personalised medicine.”
And then there is the growing problem of counterfeiting aided by the rise in online operators. Around 10% of all recorded pharmaceutical crimes have been attributed to the European arena, with the European Observatory on Infringements of Intellectual Property Rights estimating the cost at around €10 billion annually.
Manufacturing Chemist estimated the potential jobs loss at nearly 40,000, with the figure swelling to more than 90,000 jobs when indirect effects are taken into account – plus a ‘negative impact’ estimated at €17 billion, around €1.7 billion in lost government revenues.
Fortunately, manufacturers are becoming increasingly inventive with solutions that provide the competitive edge – but it has taken time.
Jonathan Wilkins, marketing director of parts supplier EU Automation and a regular commentator on the technological advances in manufacturing, explains why.
While sectors such as food and drink or automotive have ploughed ahead with automation, this has been more difficult for the biopharmaceutical sector in particular, he suggests.
“Automation is key to making the improvements the biopharmaceutical manufacturing industry needs, such as increased efficiency and capacity, while maintaining high product quality,” says Wilkins.
Easier said than done
But the necessary embrace of digitalisation too raises difficult issues, acknowledges Lustig.
Creating efficient workflows that fulfill guidelines outlined by the International Society for Pharmaceutical Engineering (ISPE) to ensure data integrity and conformal production is not easy and often, existing equipment is not prepared for the modern digital world.
Yet while regulation has acted as a partial brake, general rates of automation are increasing, states Lustig. Its adoption is intrinsic to increased plant performance, asset efficiency and plant availability, while predictive maintenance based on Big Data solutions is also growing in importance.
“There is no hard limit on automation. I would even argue that the more the process is not only monitored but automated, the better quality and safety standards can be reached. However, in many cases, the accessibility of equipment, and especially smaller lab equipment with no standardised interface, is a limitation,” he comments.
Achieving a better understanding of equipment performance is crucial, emphasises Wilkins, a process that requires a mix of automation and digitalisation. An array of sensors, as in so many sectors, harvests the data while SCADA software stores and then interprets this.
“Machine learning technology enables equipment to adapt to changes in product specification, equipment and the surrounding environment, so a production line can be altered in line with the requirements.”
The benefits can be seen in terms of achieving better regulatory compliance, predictive maintenance to guarantee greater process efficiency, plus fewer problems with failing assets and consequent downtime.
Removing levels of human intervention enhances the accuracy and precision required in biopharmaceutical manufacturing to adhere to industry regulations and the need for batch to batch consistency.
Bye bye batches?
A consequence of this is that it facilitates the transition from batch processing – relying on consecutive movement of individual units through a work cycle – to continuous processing.
The latter avoids the need for breaks between steps in the production process in favour of an uninterrupted flow.
As this can have the net effect of considerably increasing productivity while saving money on manual labour and downtime (despite initial costs), it’s no surprise that BPE’s Shott takes a similar view to Wilkins on the gains to be made: “Having the ability to model and design a new continuous process iteratively is therefore an essential step in increasing predictability of outcome and that’s exactly where BPE is helping its customers.”
Today’s pharma companies need to be more agile and scalable than ever. Companies need to manufacture greater product varieties, with shorter production runs, partly driven by the demand for personalised medicines
Gero Lustig, global segment manager, Pharmaceutical & Life Sciences, ABB
Innovative modelling techniques, that boost predictability and minimise the risk element, can create reliable and effective process scale-up when combined with continuous processing insists Shott.
“Well-established continuous process design methodology has been vastly improved through digitalisation and machine-learning algorithms to improve accuracy and predictability.”
The road to continuous processing adoption has been an uneven one though, cautions Lustig: initial high interest followed by slowdown; then, more recently, encouragement from the US Food and Drug Administration (FDA) boosted by enhancements provided by automation technology and process analytical technology.
Significant adoptions, such as Glaxo Smith Kline’s announcement of continuous manufacturing facilities in Singapore, Fujifilm’s $10 million continuous bioprocessing technology investment and UniverCell’s development of CM for the measles and rubella vaccine have also helped, says Lustig.
As in every process industry, though, it is easier to embrace innovation when one operates at scale and has access to substantial resources in terms of finance, training, personnel and strategic planning.
Facing a dilemma
It’s a dilemma for the average small to medium enterprise, Lustig acknowledges. When working with limited means, the key factor is likely to be the ability to make a considered judgement call.
“Historically SMEs have been slower to uptake and embrace 4.0, with the biggest barriers being cost, skills and the ability to assess how automation can best fit their business needs.
Today, more and more SMEs are beginning to understand that it is not a ‘one size fits all’ approach and that a step-wise approach is possible via proof of concept and pilot installations prior to wider roll out.
“Understanding how and where digitalisation and automation will add the most value to operations, starting small, and creating incremental, sustainable improvement opportunities in an agile and scalable way is enabling SMEs to get on board. This is beginning to balance out the market.”
Sealed, delivered
Pharma flow wrapping is emerging as big business
Demands for greater hygiene and regulatory standards, as well as quality control have created a greater market for specialised flow wrapping in the pharmaceutical sector.
Product manager, pharmaceuticals at ILAPAK, Christian Ballabio says it is increasingly used for overwraps to permit greater barrier protection.
“For example, packaging blisters in a flow wrap enables the use of blisters made from ALU-PVC combinations instead of more expensive ALU-ALU,” said Ballabio.
“Typically, the wrapping material will incorporate an aluminum layer, to provide a barrier to light, moisture and oxygen. This material presents a number of challenges when creating hermetic seals, owing to its thickness and rigidity.”
He notes too the rising use of ultrasonic sealing “because it is a cold sealing technique, eliminating challenges around temperature”.
Ultrasonics is popular with contract manufacturers, as it can switch easily between different wrapping materials.
“With heat sealing, operators must find the right combination of temperature, time and pressure for each different material. With ultrasonics, set-up simply involves changing the frequency via the HMI. The higher capital cost of an ultrasonic sealing unit can be justified by superior performance.”
