HIGHLY POTENT APIS
Preparative chromatography for HPAPIs at Le Mans
installation and the operation of the equipment against specifications , train the users and perform preventive maintenance . Having the appropriate analytical methods is a pre-requisite for controlling the exposure . Generally associated with product QC , they are also used to control the cleanliness of the equipment to avoid cross-contamination and protect the patient . Controlling cleanliness for the equipment and in the working environment ( surface and atmosphere ) are required to guarantee the safety of the people working in production , but also those in the labs or doing the maintenance operations . But what is an appropriate method and what are the challenges behind it ? The requirements for product , equipment and working environment control are all the same : the method must be specific , accurate , precise , sensitive , linear and robust . With HPAPIs , such as payload linkers for ADCs , the methods must be even more sensitive due to the small batch size and the low OELs . LOQ needs to be in the ng / mL range as you need to detect below 0.05 mg in production equipment .
Reference :
When qualified analytical methods are available , the actual containment performance of the collective protective equipment can be measured . The test is often done using a surrogate product ( naproxene sodium ) according to a preestablished protocol , representative of real lab or production operations . Sampling points are defined , on the operator , on the equipment , next to the weak points and in the environment . We recommend executing the protocol three times ( as for a qualification ), with three different operators to integrate the human variability , in the presence of one witness . This person ' s role is to carefully observe the execution of the protocol and support any future investigations to understand the significant gaps between the highest and the lowest results . It will be an opportunity to align all workers on the best practices . After analysis of the sample , the highest result is retained , multiplied by a safety coefficient to define the containment capability of the equipment . The outcome is , for each work station , the lowest acceptable OEL . In the case of routine production , air sampling can be done
1 : AC Tiberghien , PW Howard , R . F . Goundry , M McCormick & JS Parker , J . Org . Chem . 2019 , 84 , 4830-4836 in the workshop to confirm that the concentration in the atmosphere is below the OEL of the HPAPI . Control does not only apply to equipment . The human factor and training are key elements of the potent compound management system . Training is a continuous process , subject to efficiency checks . It starts with initial training on SOPs , making sure that the concepts are well understood . It continues with practical training at the work station according to the AMTS methodology . With time , new best practices can be identified and shared to raise the level of the entire teams . A solid continuous improvement process is needed to ensure a reliable performance and develop know-how . Communication is another key element to delivering quality services and building trust with your employees and clients . The information generated about the products , the exposure and the risks is recorded in controlled documents and shared with the teams , while clients regularly audit systems for CDMOs .
Conclusion
The supply of development and manufacturing services for HPAPIs requires specialised containment . But safe HPAPI manufacturing is not just about equipment ; it is also about expertise and essentially about people . Gloveboxes can always be purchased but company culture can only be built with time . All the functions of the CDMO have a role to play in the management of risk associated with highly potent compounds - not only those directly handling the products either in R & D or in manufacturing , but also employees not handling the products but potentially exposed to them or managing related information . •
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Bertrand Cottineau
P & D GROUP HEAD , LE MANS SITE
NOVASEP – PHARMAZELL GROUP pharma @ novasep . com www . novasep . com
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