Optimised processes in drug production: PBL relies on integrated filling line

For more than 30 years, one of Porton Biopharma Limited's (PBL) most important products has been saving children's lives. In order to meet the increasing demand, the company is currently investing in a new plant and equipment - including a filling line developed by Bosch Packaging Technology that is precisely adapted to the demanding requirements in terms of automation, safety and efficiency.

Erwinase^® is used for the treatment of acute lymphoblastic leukaemia (ALL) a type of cancer that predominantly affects children. The asparaginase enzyme is part of the treatment in combination with radio- or chemotherapy. Since its first authorisation in the UK in 1985, Erwinase^® registered in 20 countries and marketed in more than 75 countries worldwide. The drug saves the lives of thousands of children every year.

„That doesn't sound like much at first. But when we consider that these children would not have a high chance of survival without treatment with our drug, we are proud and happy about every child we treat with Erwinase^® can save us,“ says Dr Roger Hinton, Managing Director at PBL.

PBL is currently investing in additional resources with the aim of, Optimise production processes and the increasing production requirements to fulfil. This also includes the construction of a new plant with an integrated filling line, which PBL is currently implementing together with Bosch Packaging Technology (pharmaceutical product division).

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[infotext icon]The Pharma product area of Bosch Packaging Technology is one of the leading suppliers of process technology and packaging solutions for the pharmaceutical industry. The portfolio ranges from individual machines to complete lines and integrated systems for the production and processing of liquid and solid pharmaceuticals.

From manual to automatic processes

The production of Erwinase^® is Expensive and Time-consuming. It takes a long time to develop the enzyme: fermentation and preparation take several weeks before the product can be bottled. Until now, PBL has operated a very labour-intensive processWhile the vials were cleaned in an existing Bosch machine, loading and unloading, transfer and inspection were carried out manually. Accordingly, the new line is intended to automate processes to make them faster, simpler and more reproducible - but above all to eliminate the risk of contact between operator and product.

„It was clear to us from the outset that this ambitious project would require extensive design reviews to ensure the regulatory requirements to fulfil,“ explains Nigel Hubbard, Senior Project Manager at PBL. „In fact, the Documentation just as important as the actual equipment. Bosch Packaging Technology has not only put together a team with impressive technical expertise and a high level of motivation. They have also developed an easy-to-understand Documentation which contained even more information than we had expected. The Bosch subsidiary Valicare supported the project with valuable expertise in qualification, validation and quality planning.“

Over 99.9 per cent accuracy

The new line covers the entire process from cleaning and depyrogenisation to filling, capping, freeze-drying and crimping. Apart from the existing freeze dryer, all machines come from Bosch Packaging Technology.

The MLF 5044 filling and closing machine for vials operates with a Peristaltic pump and 100 per cent in-process control. With a product as expensive as Erwinase^® not a single drop must be lost. Each vial contains only one millilitre of product and must be filled with the utmost precision.

„Thanks to the peristaltic pump from Bosch, the PBL line achieved a filling accuracy of over 99.9 per cent in the FAT (Factory Acceptance Test),“ explains Sven Duske, Sales Manager at Bosch Packaging Technology.

One-way filling system and labelling

PBL opted for the PreVAS disposable filling system in combination with a peristaltic pump. The pre-validated, pre-assembled and pre-sterilised system consists of filling needles, tubes and a product bag with connector. As all parts that come into contact with the product are replaced after each batch, this reduces the risk of contamination. Contamination risk considerably. PBL made another important addition with the laser-based coding of the vials: A laser printer integrated into the VRK crimping machine will take over the labelling in future. This will print the batch number on the cap of the vial for clear traceability before a camera system verifies the result.

Very high risk management

Although PBL produces on a batch basis, the line must be available all year round and always be ready for inspection by the regulatory authorities. „We carry Simulation runs with our employees and hold regular training sessions to ensure that both people and equipment are compliant at all times. We also ensure that the sterility of machines and the environment is maintained,“ explains Mike Raine, Director of Engineering. This is why PBL relies on a Very high risk engineering level. Should there ever be a problem with a machine part, such as a power failure, additional backup generators are available. These ensure that the medicines remain protected and sterile.

Bosch has the Redundancy factor directly into the system: as soon as the vials leave the depyrogenation tunnel, they enter a closed system. The filling, lyophilisation and crimping processes are isolated thanks to three separate class A laminar flow groups with HEPA filters. These ensure an uninterrupted laminar flow - even in the unlikely event that one or more of the 14 fans were to fail. In addition, a SCADA (Supervisory Control and Data Acquisition) system monitors all critical parameters for batch release such as temperature, time and filling accuracy. The data collected and checked by the SCADA system Data is fully validated and therefore ready for an official inspection at any time.

Significant increase possible

Despite the demanding requirements, Bosch completed the line on time in Crailsheim. Following successful acceptance by PBL, the machines were dismantled and prepared for transport to the UK. There, the SAT (Site Acceptance Test) is due first, followed by the installation and operational qualification (IQ/OQ), further performance qualifications, test procedures and intensive employee training. „Thanks to the outstanding work of the Bosch team, the new plant will be ready for operation over all process optimisations that we had hoped for. This will make our daily work much easier and, together with further investments, will enable us to scale up the production of this life-saving drug.“

PBL expects both the product and the plant to be authorised for performance assessment (PQ) by the beginning of 2020 - and would therefore be right on schedule.

[infotext icon]About Porton Biopharma Limited

Porton Biopharma Limited, based in Porton Down in Wiltshire in the south of England, is the exclusive manufacturer of Erwinase^®, which is filled into vials. The company was spun out of the UK Department of Health in 2015 to give patients better access to this vital medicine and to drive forward the commercialisation of the products[/infotext].