Speciality Chemicals Magazine SEP / OCT 2021 | Page 17

HIGH POTENCY APIS
Potency and toxicity are not equivalent . There may not be a direct correlation between in vivo behaviour and in silico prediction , and the pharmacokinetics of a particular molecule cannot be fully understood until in vivo studies are carried out . Since the pharmacodynamics data needed to assess the potency level of these drugs may not be available when entering clinical studies , the classification of these compounds in early development is generally conservative . Short- and long-term dosing studies in the early clinical phases enable better-rationalised permissible exposure limits to be established . An API is generally considered potent when its eight-hour average occupational exposure limit ( OEL ) is < 10 µ g / m 3 . Anything below 1 µ g / m 3 is considered highly potent . However , these classifications are broad and the containment controls necessary vary widely across this spectrum . The most common form of hazard communication is through occupational exposure banding ( OEB ) classification , with each band being tied to generalised containment measure recommendations . SafeBridge ’ s five-band pyramid system ( Figure 1 ) is commonly known , but not universally accepted . Different organisations use systems varying both in the number of bands and the containment targets associated with each . Just as potency does not equate to toxicity , hazard is not equivalent to risk . Once the hazard of a substance is determined , it is then necessary
Figure 1 – OEB approach to assess the risk it may present . Many factors can mitigate or exacerbate the exposure risk of an HPAPI and OELs are calculated from a clinical point of departure . This is risk-adjusted by a variety of safety factors to account for interspecies extrapolation , exposure duration , inter-individual variability , toxicokinetics and generalised modifying factors . These values can be highly interpretative and based upon organisational risk tolerance . This is a good quantification of the hazard present for a molecule , but the risk of exposure is more impacted by physical and environmental factors , as these affect the likelihood of absorption . For example , most HPAPI systems are engineered to handle powders , but if a substance is in liquid or solution form , the probability of it becoming airborne , and therefore inhaled , is significantly reduced , although the risk of skin absorption is probably increased . Therefore , the containment strategy has to factor in both the hazard and the risk . Furthermore , the level of risk increases with the number and complexity of unit operations using the material . A substance that is fully contained within a single reactor presents a lower risk than one that is subjected to multiple separations , transfers or other activities that could result in loss of containment . In 2019 , GlobalData ’ s Drugs by Manufacturer database showed that , of the 532 novel drugs requiring high containment that were approved in the US and EU in 2008-2018 , 255 used outsourcing for the development and manufacture of the API . Market demand has outpaced internal investment and programmatic maturation , which has in turn created consolidated outsourcing strategies . As well as the requisite equipment and facilities , companies working with HPAPIs need to be able to develop mature processes and specialised expertise to reduce risk adequately . Preparing a facility to handle HPAPIs is capital- and resource-intensive , resulting in a high barrier to entry . It is expensive to put in the requisite infrastructure and process equipment . New molecule onboarding , containment strategy development , cleaning verification and robust operating procedures are a given , but so are emergency response protocols for a loss in containment . Smaller biotechs are neither funded nor structured to support that level of capital expenditure and long-term development of systems . Even larger organisations have found it economically burdensome . Hence , outsourcing these activities is commonplace .
Selecting a partner
With rising demand , many organisations are expanding HPAPI capabilities . This makes selecting the right partner challenging . Five considerations in finding the right partner are :
1 . Purpose-built facilities 2 . Flexibility & customisation ‣
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