Figure 3 – Supply chain considerations & regulatory requirements
late-stage intermediates and APIs . These changes need to be considered carefully when introducing new sources into processes that are established , because the impact on the process can be significant and , in many cases , not easily palatable .
When the final product has been made previously , procurement needs to closely map their purchases to the findings found from previous process development activities in the lab , particularly in relation to impurity control . However , when scale-up and development projects transfer to other service providers to avail of in-house chemistry expertise , such as biocatalysis , physical sciences and flow chemistry , this opens up alternative strategies for the supply of materials .
Within the supply chain , the strategy on these occasions differs slightly because a flexible , agile approach is crucial . The chemistry group will probably need to change the process during the tech transfer and development phase resulting in changes to material volumes and sometimes the actual CRM requirements .
Ideally , when specialist technology is deployed , this results in the process starting from readily available starting materials . The success of procurement ’ s involvement depends on whether it can keep up to speed with the chemists ’ changes . Fluid communication channels via regular procurement-led review meetings with both the internal and external stakeholder base will mitigate this risk .
Almac supports this through the deployment of technologies and the ability to manufacture from kg to tonne for CRMs including intermediates , registered starting materials ( RSMs ) and APIs . This integration has proven paramount to allow seamless interactions of the final stages of the cGMP API team ( s ) and the integration of the CRM manufacture within the same organisation .
The ability to back-integrate n-1 , n-2 steps of chemistry internally is essential for maintaining timelines and rapid delivery to support the later stage API steps . Figure 2 summarises the company strategy .
Adapting to alternative processes
Most of what has been discussed assumes that customers ’ expectations and their raw material risk approaches align with the CDMO ’ s own CRM strategies . This is not always the case and therefore alternative approaches to CRM supply must also be accommodated .
Some developers like to provide their own CRM ; some invest time in vendor selection early and get it right first-time , organising supply chains and manufacturers with quality building blocks from
project kick-off . Often those with larger resources are happy starting from a much more basic material specification in the early phase to develop a better understanding of the APIs impurity profile and highlight any potential impacts on the downstream chemistry . On rare occasions , developers may even ask their outsourcing partner to source and purchase the material ’ s known impurities so they can be ‘ spiked ’ during early-phase batch manufacture .
The rational for this is that the earlier a more comprehensive review of the impurity profile from the CRM can be evaluated in the final product allowing the chemistry team to technically manage and consider any unpurgeable impurities from the materials in the later synthetic steps . This is rare , but it does demonstrate how seriously companies consider the quality and impact of their key CRMs and the lengths that they will go to understand fully all the chemical characteristics that could have a profound impact on their final API .
CRM readiness for commercial
From a material supply perspective , in an ideal world the outsourcing partner for CRMs will be involved in the project prior to any late-phase commercialisation activities to ensure prudent selections have been made .
48 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981