PHARMACEUTICALS require only one or two campaigns / year , the facilities were designed to be flexible and modular , readily able to adapt to changing production needs and product lines .
Process challenges
Developing a robust manufacturing process for oncologics and orphan drugs generally parallels the development pathway of traditional small molecule assets . However , unlike their lower-potency counterparts , development activities may generally be more difficult , since proper engineering controls and handling practices must be employed to ensure worker safety .
This calls for standard operating procedures and laboratory practices as well as engineering controls for common activities undertaken in the development cycle . Examples include restricted travel and access to process chemistry and analytical laboratories ; employing key signage for awareness ; and incorporating additional containment and personal protective equipment for all key operations . These support the standard development activities expected for any drug candidate .
When it comes to route scouting and process optimisation , developing critical processing parameters and acceptable operating limits should be done using Design of Experiments ( DoE ). For this , a CDMO needs experienced teams of process development chemists , who are skilled at developing commercial assets on critical timelines . Where appropriate , continuous flow manufacturing can be used to improve purity , safety and robustness , and reduce operating costs .
Ensuring the accuracy and reliability of analytical methods is crucial . The analytical R & D team should complete full method development and validation to lock in robust methods for release of intermediates and final product . Additionally , the team should develop and implement all in-process testing and process analytical technology in support of process control .
Process validation , the final step in preparation for small-volume commercial manufacture , involves the manufacture of process performance qualification batches to ensure the final manufacturing process ( and supporting analytical methods ) is robust and reliable . Transitioning from the clinical batch paradigm to commercial production requires meticulous planning and execution .
Quality & regulatory compliance
Regulatory compliance is a critical aspect of manufacturing oncologics and orphan drugs . The processes must adhere to Good Manufacturing Practice and meet stringent regulatory requirements . Any CDMO considering adding a commercial API production offering to a traditionally clinical API footprint must consider how to ensure a robust commercial quality system without ‘ hamstringing ’ the flexibility of the early clinical development team .
Cambrex addressed this at CHP by implementing fundamental quality system updates designed to be phaseappropriate , evolving from a flexible early development system to a robust later-stage commercial platform that satisfies stringent regulatory demands . This ensures that the manufacturing process is compliant at every stage .
Specifically , early clinical programmes have an approach to quality that provides operational freedom with proper documentation , i . e . the ability to utilise a nimble deviation process to allow last-minute process changes or material / solvent swaps . Proposed changes for late Phase II , Phase III and commercial stages are subject to much higher scrutiny because of the standards applied to late development .
Additional challenges
Small-volume manufacturing can be relatively cost-prohibitive because the traditional economies of scale are never realised . Such challenges can be daunting for any drug discovery company but should be offset by earnings after approval .
Traditionally , developers of oncologics and orphan drugs tend to be small and medium-sized companies with limited resources . As the costs of API development do not dramatically change based on annual volume , lack of return on investment can become a critical hurdle . Outsourcing key development activities to a CDMO with facilities committed specifically to these assets can help mitigate overall development costs .
Such collaboration between CDMOs and pharmaceutical companies is crucial for the successful development and manufacturing of oncologics and orphan drugs . Forming strategic partnerships with innovators to stay at the forefront of technological advancements and regulatory changes is vital . These partnerships enable knowledge and resources to be shared , ultimately leading to more effective and efficient manufacturing .
Conclusion
The evolution of process development and manufacturing for oncologics and orphan drugs is marked by significant advancements in technology , regulatory compliance , and collaborative partnerships . The ability to handle higher potency APIs and having facilities dedicated to manufacture of small volume products are critical elements in addressing the unique challenges of these critical therapies .
By embracing these advances and fostering strategic partnerships , CDMOs are well positioned to lead the way in the development and manufacturing of oncologics and orphan drugs , ensuring that these critical therapies reach the patients who need them most . ●
Reference : 1 . IQVIA Institute , August 2020 : FDA orphan drug designations & approvals
Dan Bowles
VP , GENERAL MANAGER , CHP
CAMBREX k + 1 336 841 5250 J dan . bowles @ cambrex . com j www . cambrex . com
SEP / OCT 2024 SPECCHEMONLINE . COM
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