HIGHLY POTENT APIS product . Once the data is collected , it is reviewed and used to categorise the product by toxicity level . On occasions , very little or no specific data is available . In these cases , categorisation is made by default , meaning that vectorised cytotoxic chemical entities must be put in the highest toxicity band . When more data is available , the OEL may be calculated . The second dimension is the evaluation of the exposure level to HPAPIs that should be done for a specific unit operation at a specific work station . The parameters to consider are the physical form of the product , the operating mode and collective protection . Personal protective equipment ( PPE ) is deliberately ignored at this stage , as it should always be our priority goal to ensure workers protection with engineering devices . PPE comes aftewards , as an additional safety net or when collective protection solutions are not sufficient . When the product toxicity ( danger ) and the exposure levels are defined , the risks can be mapped .
Risk mitigation in process development
To mitigate risk , everything starts from the process development phase , where the best synthetic route and an optimised process will be designed . As the toxicity of the final API cannot be reduced , we will focus on the toxicity of the other compounds and design a synthetic route to reduce the number of highly potent intermediates . In one example , to which the former Novasep contributed , AstraZeneca sought a route to Tesirine . This is a PBD payload linker for ADC and is one the most toxic payloads with an OEL below 5 ng / m 3 / 8h . The original route was efficient but involved eight highly potent steps . The toxicity was due to the PBD ring . Using the same advanced intermediate and generating the PBD moiety last in the process , the number of highly potent compounds was reduced to three without affecting process efficiency . 1 After designing the synthetic route , the process will be optimised while respecting the strategy presented hereafter . First , the optimised process should reduce the handling of dry powders as much as possible . When stability is sufficient , highly potent compounds should be kept in solution and isolation should be limited to the minimum required . That is why , for example , highly potent solids will be solubilised before being loaded into the reactor .
HPAPI lab at the Le Mans site
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