Hot Runners / Case Study Plastics in the service of medicine
Formenbau Glittenberg supplies injection moulds equipped with Witosa hot runner systems for vital medical technology products to Celon Pharma.
In our issue 10 of ETMM - The Magazine (the original publication of this article), we did not mention the author of this article, Ravan Graubner. We apologise for this mistake.
Mostly detached from developments in other industrial sectors, medical technology continues to be a rapidly growing industry with great innovative strength. Diverse new products with new types of materials for a wide variety of applications offer a wide range of applications, in particular for the field of injection moulding technology. Anyone who wants to play here, however, faces great challenges, and not only in terms of quality, innovation and cost efficiency. More than anything, the rules and regulations applicable in this sector must also be mastered.
Compared to other industries, the quality requirements are very high. The documentation requirements are extensive. Production in accordance with GMP (Good Manufacturing Practice) is mandatory. This requires permanent monitoring and compliance with hygiene regulations and complete documentation of all process data over many years. Entry into the medical technology industry as a supplier is therefore difficult and requires a great deal of effort. Located near Warsaw, Celon Pharma S.A. is still a relatively new pharmaceutical company. It was founded in 2002 by Mr Marciej Wieczorek. Today, the company employs 400 people in Poland, including 70 scientists, and distributes medicines in more than 50 countries around the world.
Developing a discus inhaler
The great strengths of Celon Pharma S.A. are their extensive research and development facilities. The company has two fully equipped laboratories that develop pharmaceutical products for the treatment of cancer, neurological disorders, diabetes and other metabolic disorders. Another focus is on the development, manufacture and distribution of specialised generics.
The production sites of Celon Pharma S.A. have attained appropriate GMP approvals. The GMP certificate enables the company to obtain authorisations for sales and marketing of drugs in all EU countries. Existing quality standards for production are thereby guaranteed.
The Glittenberg Group, based in Frankenberg in northern Hesse, was founded in 1990. It consists of Formenbau Glittenberg (mould-maker), Kunststofftechnik Glittenberg and Witosa Hot Runner Systems. The group currently employs over 150 industry professionals and is represented worldwide with its products.
With the help of an EU funding programme, the European Regional Development Fund, Celon Pharma S.A launched the PIKCel project in 2014. The aim of this project is to use a PI3K inhibitor, which is used to treat various types of cancer, for the treatment of lung diseases such as asthma or COPD. The method of administering this medicine is inhalation.
As part of this project, Celon Pharma faced the challenge of developing and producing a fully functional discus inhaler. The customer was requiring from the outset that all parts for the inhaler be manufactured with the highest precision and accuracy in order to ensure completely reliable functionality. Deviations from the required dimensions and the maximum tolerance of ± 0.02 mm of the individual components of the inhaler are not permitted, as the function is otherwise impaired.
For example, when operating the inhaler, the blister must be transported exactly to the next medication reservoir, opened, the used conveyor belt wound up and the unused stored. The drug must then be completely pulled out of the opened blister and transported through the mouthpiece by a slight negative pressure, as when inhaled by a small child. On the other hand, during handling of the inhaler, the drug must not fall out of the reservoir of the blister prior to inhalation.
Within this complex mechanism, a total of 14 components must work together perfectly to achieve the desired function. Clean and smooth functioning of all moving components is an absolute prerequisite. Failures or contamination, for example, due to material abrasion, are not permitted.
“The demanded precision for the exact interplay of all parts of the inhaler, which has to remain absolutely constant over a planned production number of 400 million pieces per year and fully automatic assembly, was only one of the yardsticks we used to choose a suitable tool and hot runner manufacturer,” says Artur Wieczorek, project manager at Celon Pharma.
The highest uniform quality and hygiene standards founded on validated processes and a certified QM system were another basis. Moreover, there were also the regulations prevailing in medical technology, such as the GMP requirements that require the implementation and exact documentation of risk assessments for the injection moulding tools. In other words, qualification and process validations had to be performed to create and document appropriate process capability certificates.
Absolute precision is a requirement
With this ambition, Celon Pharma went in search of a suitable partner in Poland and Germany, approaching the Glittenberg Group in 2014. Artur Wieczorek comments: “The subject of plastic injection moulding was completely new to us. We had an inhaler in our hands and in no time needed millions of them. Therefore, short and direct communication channels were very important to us in this phase. We needed a professional partner who could immediately understand and implement our request.”
Celon Pharma was determined to get everything from one provider, including the design, the tools and the hot runner systems. They wanted only one point of contact to shorten transmission times and exclude communication losses. Another challenge of this project was the very short timeframe. Some 14 injection moulds including hot runner systems had to be realised in less than a year, starting with the article. Added to this were the high quality requirements for the tool surfaces, which are demanded by the U.S. market. As a result, the quality requirements for toolmaking and the hot runner manufacturer were correspondingly high.
“Since we are at home in the medical technology industry, we saw from the outset the enormous effort that we would have to put into planning the tools in order to be able to fulfil the guidelines of the industry,” says Torsten Glittenberg, managing director of the Glittenberg Group. Based on the requirement specifications and the performance specifications of the customer, a corresponding product specification was drawn up and determinations for the cleanroom suitability of the injection moulding tools and hot runner systems were made. Among other things, this involved the selection of suitable corrosion-free materials for the tools and hot runners. Maintenance and inspection plans and specifications for cleanroom-compatible cleaning, lubrication and storage of tools were also created.
Artur Wieczorek comments: “The design of the article and the documentation were prepared very well by Glittenberg. The communication was always perfect. Our very challenging timelines were always well kept and even undercut.”
Design looped to perfection for medical use
In 2014, the first parts were produced from the new tools. They were then optimised in several design loops and adapted to the strict article geometries required. The first inhalers were intended for the U.S. market. In 2016, production started for the entire European market with an initial volume of one million units. Meanwhile, the inhaler has gone through its tenth design loop.
“We have grown with the demands of the market. Glittenberg was always open for any help and ready for adjustments. The desired changes were implemented in a completely uncomplicated way,” adds Artur Wieczorek, assessing the co-operation with Glittenberg.
In the meantime, 35 injection moulds equipped with hot runner systems and over 300 hot runner nozzles from Witosa have been delivered to Celon Pharma. Under cleanroom conditions, the components for approximately twelve million inhalers per year are manufactured on 16 injection moulding machines, then fully automatically assembled, provided with blisters, and tested.
Celon Pharma is currently running twelve drug development programmes funded by the European Union. One special field of research in this programme is the administering of the drugs by inhalation. A current programme called “Disc” aims to develop this method of administering the drug for treating depression by means of an already known anaesthetic.
While currently available depression treatments show therapeutic effects only after a few weeks of regular medication, several clinical studies have demonstrated a direct and long-term antidepressant effect of the anaesthetic. Patients should be able to take the drug themselves and control the dose administered, thanks to the developmental experience of Celon Pharma.
Because of the foreseeable increase in demand of the order of 400 million units per year, Celon Pharma now plans to use further high-cavity tools for very fast cycle times.
“The big challenge for us is to implement them with all the requirements in the medical technology industry. That is very complex. Nevertheless, we are facing up to this challenge and will continue to serve our customers with the familiar quality,” guarantees Torsten Glittenberg.