Six Sigma methodology has enabled one Irish medical device company to significantly improve the speed and quality of production of its acute care hospital nebulisers. Aerogen, through a detailed analysis of its manufacturing process, has introduced statistical process control (SPC) for its flagship product, the Aeroneb Solo. This has led to faster production times, lower costs and reduced inventory while maintaining the safety, performance and reliability of Aerogen products.
Aerogen is a specialty medical device and drug delivery company specialising in the design, manufacture and marketing of nebulisation systems aimed at the critical care respiratory market. Founded in Galway in 1997, it specialises in acute care aerosol drug-delivery equipment and its Aeroneb products treat patients on life-support ventilation, as well as home-care offerings, in over 65 countries.
The company’s patented vibrating mesh aerosol technology is an integral part of its drug delivery systems. This technology allows drugs to be nebulised into a fine particle mist that can be absorbed through the lungs. It is covered by over forty patents and forms the core of all the Aerogen products.
"Aerogen nebulisers incorporate the vibrating mesh technology, which produces millions of sub 5 micron sized droplets per second, enabling controlled, deep lung aerosolised drug delivery,” explained Colm McGuinness, senior development engineer with the company.
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“The patented technology consists of a domed vibrating mesh aperture plate, which receives liquid drugs on its top surface. Through the use the plate’s unique geometry and vibration, it extrudes the liquid through the plate vibrating at 130,000 cycles per second. Then, on release, it forms a fine droplet mist to create the characteristic aerosol.”
The fine particle mist enables drugs to be absorbed through the lungs while maintaining their integrity, providing a unique level of efficiency for the acute care market respiratory market.
PRODUCT DEVELOPMENT
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Aeroneb solo action[/caption]
Aerogen’s first product was the Aeroneb Pro, a multi-patient use device that offered the latest nebuliser technology to hospital acute-care facilities. In 2007, the Aeroneb Solo, which was a single patient use device featuring the same proprietary technology, was launched. It soon became the lead product, with over 500,000 on track to be sold this year, maintaining its 40% year on year growth.
The Aeroneb Solo micropump nebuliser helps patients to breathe more easily, ensuring targeted drug delivery to the smallest airways in the lungs by producing a fine-particle, low-velocity aerosol optimised for targeted drug delivery. Its effective dose delivery of physician-prescribed inhalation solutions means that it can be safely used with all patient groups. The silent operation of the Aeroneb Solo allows it to be used in paediatric and neonatal intensive-care units, where noise levels must be kept to a minimum.
The rise in market demand, coupled with the development and validation of robust manufacturing processes, has proven to be the impetus for the company’s integration of SPC on the sampling and performance testing (droplet size and delivery rate) of the Aeroneb Solo nebulisers.
Through analysis of the variability of the Solo process, it was found that the occurrence of special cause variation was extremely low, resulting in the ability to rely on statistically significant samples to monitor the process output. SPC testing was seen to reduce handling, minimising the risk of contamination as well as reducing the manufacturing time.
“SPC has come at a time when Aerogen is on an upward trajectory of sales growth, resulting in a need for increased production capability and speed in order to meet market demand,” said McGuinness. “It’ll be a major step forward in our production capabilities and it comes out of our continued investment in R&D and manufacturing processes.”
Aerogen currently employs a growing team of 60 people – primarily science and engineering graduates and with many of these at PhD level. The company has registered over 40 international patents within the aerosolised drug-delivery market. It also partners with biotech and pharma companies to develop and deliver specialty aerosol drug solutions, utilising its proprietary vibrating mesh technology platform.
NANOPARTICLES
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Generator close up - an aperture plate[/caption]
Nanoparticles are rapidly becoming the focus of multiple new drug delivery modalities,– especially in the pulmonary field. Nanoparticles offer a variety of advantages including, but not limited to:
- increased drug targeting;
- enhanced solubility of drug;
- sustained and/or controlled release of drug;
- potential for drug internalisation by target cells; and
- potential for dual therapeutic and diagnostic, that is to say, theranostic applications.
Aerosol-mediated delivery via an aerosol generator is the preferred method of delivery to the lung and, as such, the effect of the process of aerosolisation on the nanoparticles must be considered.
Aerogen has engaged with a variety of researchers in the development, characterisation and exploitation of a variety of different nanoparticle systems for targeted delivery to the lung. These nanoparticles are representative of a variety of nanoparticle types including simple high-capacity vector systems, functionalised nanoparticles for increased targeting specificity and also theranostic systems.
The company’s research work to date has resulted in the development a variety of nanoparticle systems harbouring therapeutic utility, compatible with its proprietary mesh technology. This technology has demonstrated superior performance with nanoparticle formulations when compared with jet and ultrasonic nebulisers for the purposes of aerosol compatability.
A suite of protocols has been developed for rapid screening of candidate nanoparticles and multiple preclinical studies with a range of candidate formulations have already been undertaken.
COLLABORATION
Aerogen works with a network of collaborators to develop these novel nanoparticles, co-ordinated through its membership of the Competence Centre for Applied Nanotechnology (CCAN) in Ireland. With CCAN, its technology has been used in pre-clinical studies working in the anti-cancer field, where highly insoluble therapeutics encapsulated in nanoparticles complexes have been successfully delivered to the lungs.
“Research and development forms the core of Aerogen’s product strategy,” said McGuinness. “Last year, we officially opened our dedicated aerosol science laboratories and R&D laboratories on site here in Galway. Aerogen typically invests up to 30% of operating expenses in R&D so, with such a focus on this part of the business, we plan to further expand our portfolio of products and markets.”
According to McGuinness, the next step for Aerogen will be to further its work with drug partnership programmes – something it began with its partnership with Dance Pharmaceuticals, an aerosolised insulin product that is currently in clinical trial phase.
“The future looks bright for the Irish indigenous medical device sector,” the senior development engineer concluded. “Ireland is a world leader when it comes to technology such as drug delivery and we have a lot of very talented engineers in this area. This can only strengthen the sector in the years to come.”