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Handling potent APIS with care and confidence

5 October, 2016 | ChargePoint Technology

Potent active pharma ingredients require ultra careful handling and containment. ChargePoint highlights the challenges and how they were effectively and safely dealt with for contract developer and manufacturer Fermion at Espoo.

Finnish contract development and manufacturing organisation (CDMO) Fermion has developed and manufactured active pharmaceutical ingredients (APIs) at its FDA-approved facilities since the 1970s.

Last year, investment in its Espoo site increased significantly production capacity of Occupational Exposure Banding (OEB) 5 compounds at the kilo scale. The floor space was expanded from 200m2 to 580m2 and the company saw the installation of a bespoke production unit.

Its design comprises a plant with glass lined vessels along with a Hastelloy C-22 reactor for more demanding synthesis campaigns.

The site at Espoo forms just one small part of Fermion’s highly potent API development and manufacturing capabilities.

The extension of its Hanko commercial production facility, planned for completion in 2018, will provide more production space for OEB4 and OEB5 category APIs.

‘As a manufacturer, safeguarding production staff is of primary concern when developing products and planning for future growth, both in technological advancement and the quality of finished APIs,’ says Jarkko Helminen, Process Development Manager at the Fermion Espoo site.

‘ChargePoint Technology of Liverpool, UK, alongside local partners Thurne Teknik of Stockholm, Sweden, created the solution to meet and maintain our commitment to the safety of our staff during the processing of APIs at our kilo facility in Espoo.’

Despite its obvious benefits to the patient in the final dosage form, the API, along with the intermediates used to synthesise it, can pose significant risks to the health and well-being of workers who handle them in bulk form during manufacture.

Today it is common for CDMOs to operate multipurpose facilities because of the range of products they create and develop. This strategy is evident in many R&D and production facilities but it poses the challenge of handling multiple ingredients without any risk to product quality.

The requirements of reducing both the potential for contamination and the risk of exposing production staff to hazardous chemicals makes the transfer of powders from one process to another a key area of concern for Fermion, and one that is amplified with OEB4 and OEB5 APIs.

As a result, ChargePoint PharmaSafe® containment valves were selected for the transfer of raw ingredients from the dispensing stage to reactors for synthesis.

Split Butterfly Valve (SBV) have been used as an operator safety device within fine chemical and solid dose pharma production for more than 20 years.

They minimise the amount of airborne particle exposure during the transfer of potent powders from one process step to another.


One device - two halves

The fundamental feature of all SBVs is that they consist of two halves, namely the active (Alpha) unit and the passive (Beta) unit.

Each half consists of half of the ‘butterfly’ disc, which is sealed against the main body via an elastomeric seal to create the containment necessary.

In Fermion’s kilo facility process, the active unit is attached to the stationary process equipment, namely the dispensing isolator and the reactor vessels.

The passive units are connected with the mobile ChargeBag® powder containers.

The common interface allows operators to transfer batches of material without breaking containment between steps. The DN50 (2in) valve size was selected for this cGMP lab scale R&D process for small scale transfers of less than 10L.

Chemical and high temperature compatibility is provided via construction material choices of C22 and fully fluorinated perfluoroelastomer (FFKM) seals. The pressure-resistant design ensures process safety at all times, with additional options for using the valve as a viewing port with its sightglass accessory.

The ChargeBag® transfer bag was an ideal alternative to rigid containers for Fermion. Its single-use, disposable nature eliminates the need for cleaning – with obvious savings on Fermion’s operational resource – and is ideal for multipurpose plants.

The PharmaSafe® system provides containment performance to less than 1µg/m3 for OEB5.

The technology has been fundamental to Fermion’s OEB4/5 manufacturing capabilities at the kilo facility, with the additional benefits of being easy to integrate and retrofit into its existing plant and providing scalable technology for future expansion (it is available up to DN250).

ChargePoint Technology’s devices, delivered alongside partner Thurne Teknik, have allowed Fermion to meet its ambition of growth and continue its devotion to safety and quality.

This article was originally printed in Cleanroom Technology, Oct 2016.