HIGH POTENCY APIS
and room pressurisations to control the area where the potent compounds should remain , whether in a room or within a piece of equipment .
In terms of equipment , room and / or lab airlocks are necessary to control the movement of materials and equipment . One of the key improvements leading to a safer handling of the HPAPI has been the use of containment technologies . The development of isolators , gloveboxes and closed systems has revolutionised the safe handling of HPAPIs . These technologies minimise the risk of exposure to highly potent compounds , protecting both workers and the environment .
Need for monitoring
Nevertheless , once the facility and equipment controls are in place , a company should perform internal testing to measure the performance of its systems alongside the verification of the efficiency of standard operating procedures used to conduct the different handling procedures .
This is typically completed by the monitoring of an easily detectable placebo compound used during operation mimicking those involved for the handling during manufacture , bagging or sampling of the potent compound to determine at what points , if any , HPAPI in powder or solid form is detected outside of the containment .
Such monitoring would typically include sampling collection on a person , in the room , in the airlock , or even in the clean area or hallway leading to it . Minimal levels may be detected , but the level should not exceed the standards set for the equipment being tested and recommended as suitable for a given OEL band .
The last point for consideration is related to analytical monitoring tools . As the OEL decreases , the capability of the analytical technology to quantify lower level is paramount . While more and more single-use equipment is involved in HPAPI manufacturing , ‘ carry-over ’ calculations between processes are required in order to demonstrate successful mitigation of cross-contamination .
Regulatory bodies are also requiring manufacturers to demonstrate periodic demonstration of qualification of the containment efficiency and therefore the mitigated risk of crosscontamination between batches of different HPAPIs , or worse , between HPAPIs and non-HPAPIs .
Conclusion
HPAPI manufacturing can be complex and requires the appropriate containment strategy and experienced work force . As part of any outsourcing programme , it is necessary to identifying a partner with the capacity and technical capabilities and also the experience . From a formal due diligence process to a more routine Project Needs Assessment , the critical attributes that a service supplier needs to demonstrate can be summarised as :
• Employees ( scientists , engineers , analysts , and other operators ) with knowledge in the highpotency space and a dedicated training programme ensuring their handling competency
• Facilities and procedures that ensure appropriate engineering controls are in place to guarantee the safe handling of the compounds
• Cleaning and verification procedures that prevent crosscontamination with other drugs within the facility and containment monitoring
• Regulatory track record ( FDA , EMA , HMRA etc .)
• Project track records that validate the site ( s ) competency across the difference clinical phases of pharmaceutical development ●
References : 1 : ADC Contract Manufacturing Market - 4th Edition , 2020-2030 2 : Global Data reports
Jean-Francois Carniaux
VICE PRESIDENT & GLOBAL API TECHNICAL LEAD
PIRAMAL PHARMA SOLUTIONS k + 44 7467 816719 J jean-francois . carniaux @ piramal . com j www . piramal . com
20 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981