HIGH POTENCY APIS
design eliminates open handling ; the reactors remain closed , guaranteeing complete containment .
The hood ’ s air inflow and exhaust exceed 1,600 m 3 / hour , with no recirculation , maintaining the aforementioned OEL of 10 ng / m 3 , suitable to handle compounds of Category 4 ( 1-0.10 µ g / m 3 ) and 5 ( 100- 10 ng / m 3 ). For this 35 m 2 production lab , the air supply is around 3,200 m 3 / hour and the air exchange rate is 30 .
The glovebox features a 1.1 m 3 main chamber with four gloves and a 0.4 m 3 airlock with two gloves . It is outfitted with H14 push-push filters for both intake and exhaust , complemented by F96 filters internally . 3 , 4 A police filter follows the dual H14 filters on the exhaust line , with pressure switches for high-pressure alarms and Magnehelic gauges for mechanical pressure monitoring . The target OEL for work at the glovebox was also set at 10 ng / m 3 .
The glovebox is directly connected to a drying oven , with a door that opens internally , ensuring a contained environment . This equipment array guarantees full containment , effectively controlling the risk of exposure to HPAPIs .
Workflow
The process workflow is as follows : 1 . Active solids are prepared within the glovebox , weighed and either suspended or dissolved in solvent within laboratory glassware 2 . These preparations are then transferred to the reactor beneath the FWP via tubing , using a nitrogen overpressure . Liquid reagents are introduced into the reactor in a similar fashion but outside the glovebox , ensuring a confined system throughout the process 3 . Post-reaction , the resulting suspension is transferred onto a sintered filtration bottle within the glovebox , then dried in the oven With this strategy , many different chemical reactions have been carried out safely ( including peptidecoupling , protection and deprotection steps , nucleophilic substitutions and saponification ) and further chemical transformations could be performed in the future . The new lab has already supported various other chemical operations like extraction , distillation , dosing with temperature control and crystallisation .
Once dry , the product is fully analysed in a QC lab equipped to handle compounds up to Category 5 . Downstream chemistry can involve chemical steps carried out at Vionnaz or other company sites , for example antibody – drug conjugation . Alternatively , it may entail purification through chromatography ( flash , MPLC , HPLC ).
Carbogen-Amcis has extensive experience in preparative chromatography ( flash , medium and high pressure ), even within HP environment . Safety considerations are paramount during this process . The loading of the feed , collection of fractions and unpacking of the column must all be carefully contained . Specifically , the feed is prepared within a glovebox and then transferred onto the column using a feed pump .
Fractions are collected within the FWP . Finally , the column is unpacked using an endless liner to ensure full containment , and the bag is sealed using an ILC Dover CrimpLoc .
The selected fractions undergo lyophilisation using a tray freeze-dryer with a 25-litre capacity . Lyoguard trays are employed during this process . Additionally , the freeze-dryer is connected to a glovebox , facilitating the unloading of the trays and the confined packing of the product .
When production has been completed , the glovebox , the FWP and the entire room are subject to thorough cleaning as per our protocols . Effective cleaning is achieved by swabbing and HPLC analysis .
The product is sampled , packaged and the container cleaned for safe removal from the glovebox for storage or further use . At this stage , HPAPIs can either be shipped to the customer or to the site in Saint-Beauzire , France , for formulation into the final drug product . ●
Configuration of the glovebox
* - Also contributing to this article was Cédric Moren , senior maintenance manager
References 1 : https :// www . persistencemarketresearch . com / market-research / high-potency-active-pharmaceutical-ingredients-market . asp 2 : https :// www . mordorintelligence . com / industry-reports / highpotencyapis 3 : H14 designation corresponds to a high-efficiency particulate air ( HEPA ) filter classification . Specifically , an H14 filter has an efficiency of ≥99.995 % for particles in the size range of 0.3-10 micrometres . The push-push mechanism likely refers to the filter ’ s installation or replacement method , allowing for easy and secure filter changes within the containment . 4 : The F9 designation is based on the European standard EN 779:2012 and pertains to the performance criteria that air filters must meet . These filters are designed to have an initial efficiency of > 98 % for particles with a size of ≥0.4 microns
J j
Patrick Gay
MANAGER PR & D
CARBOGEN AMCIS patrick . gay @ carbogen-amcis . com www . carbogen-amcis . com
JUL / AUG 2024 SPECCHEMONLINE . COM
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