HIGH POTENCY APIS to bind and inhibit some enzyme or receptor that are either specific of , or overexpressed by , cancer cells . This high selectivity increases the activity of these drugs , moving towards HPAPIs with an improved therapeutic index , which is a key characteristic to assess the relative safety of a drug particularly for cancer .
In any case , the production and handling of these new API requires the use of containment levels during manufacture that guarantee an occupational exposure limit ( OEL ) for operators below 10 ug / m 3 or even 1 µ g / m 3 in some cases . High containment is also required to avoid the risk of cross-contamination during handling . For this reason , Olon has invested heavily in the last few years to increase capacity at several sites to guarantee production in batch sizes of up to hundreds of kg .
As already mentioned above , the second strategy to increase the therapeutic index of the cancer drugs is to deliver the highly cytotoxic drugs , which cannot be used ‘ as is ’ due to their high systemic toxicity , in proximity to the cancer cells . This approach lead to the development and use of ADCs which combine the effective killing power of small molecule cytotoxins ( payloads ) and the highly specific tumour-targeting ability of monoclonal antibodies ( mAbs ).
Need for expertise
The development and manufacture of an ADC are complex tasks , requiring the solution of many challenges for the parallel production of the mAb and payload , which then have to be conjugated . Finally the final product must be fill-finished under aseptic conditions . Additional complexity arises from the need to perform certain operations in high-containment facilities because of the toxicity of the materials , particularly the payloads and the payload-linker system .
ADC manufacturing is highly challenging because they require specific capabilities to handle different modalities with strict containment regulations , in dedicated facilities
Large-scale high-containment facility
following long synthesis , critical reactions and purification steps with all of these operations being done under high containment .
Moreover , the handling and manufacturing of these compounds requires not just new facilities , but the availability of an integrated system in which all the activity carried out at the site must be controlled , starting from the storage of the incoming material , intermediate and final product , their dispensing and handling and finally the treatment and disposal of all the wastes . The whole system must also be challenged with failure mode and effect analysis to guarantee high containment , in case of any deviation from standard practices .
This required high level of control ensures the safest environment for ADC payload-linker production and product integrity , that can only be reached leveraging over decades of expertise in containment for cytotoxic anti-cancer production , focusing on full control of crosscontamination , operator protection and extensive training .
For these reasons it is not easy for a newcomer to enter into the business
guaranteeing the assurance of supply of the products , the GMP requirements and industrial hygiene rules mandatory for the manufacturing of these compounds . There is no substitute for years of expertise in containment for cytotoxic anti-cancer production , and the willingness to continue investing in new levels of safety and efficiency .
Olon has recently invested in a € 22 million facility for ADC payloads and linkers . The ultra-high-containment production line , reaching a containment level OEB 6 ( target OEL 10 ng / m 3 ), will produce high-potency and toxic products , such as cytotoxic payloads and payload-linker system for new ADCs . ●
References : 1 : www . alliedmarketresearch . com / oncology-cancer-drugs-market 2 : www . fortunebusinessinsights . com / oncology-drugs-market-103431 3 : www . precedenceresearch . com / oncology-market #:~: text = The % 20 global % 20oncology % 20market % 20was , total % 20market % 20 share % 20in % 202021
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Giorgio Bertolini
SENIOR VP , R & D
OLON GROUP gbertolini @ olonspa . it www . olonspa . it
JUL / AUG 2024 SPECCHEMONLINE . COM
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