HIGH POTENCY APIS
Figure 1 – HPAPI exposure banding at SK
on-site qualification ( new equipment is subjected to site acceptance criteria with respect to containment capabilities ) to ongoing verification of its performance via a combination of air and surface swab samples . A well-established chemical risk-assessment process should be followed where multiple risk factors are considered . Employee , task and substance risk factors are assessed , and actions are taken to reduce risks to employees ’ exposure as needed . Results from the IH monitoring programme inform the risk assessment and provide analytical evidence of the suitability of the controls in place . The risk assessments are maintained throughout the lifecycle of the material on site and should be reviewed periodically . A robust SHE management system is also paramount to ensuring a safe and effective approach to handling HPAPIs . Such a system should be organised around an experienced SHE team and an engaged and safety-conscious workforce . Finally , a comprehensive training programme is needed to provide employees with adequate knowledge and skills for handling HPAPIs .
Modified approach
Based on its long-standing experience , SK Pharmteco has identified opportunities to adapt the approach for handling HPAPIs for maximum manufacturing flexibility while maintaining adequate safety controls . Administrative and PPE controls can thus be adapted when handling HPAPIs . HPAPIs with OELs of < 1.0 µ g / m 3 can be manufactured in facilities that are set up to handle them . In those facilities , various administrative controls are typically in place , including the use of PPE within the facilities to address the handling of these materials . Based on the outcome of an extensive swabbing programme to assess the extent of residual HPAPIs on equipment and a robust equipment integrity and performance assessment , the risk of personnel being exposed to high levels of HPAPIs can be confirmed to be low . On that basis , administrative and PPE controls can be adapted depending on the potency of material being handled in those plants . The level of PPE required is commensurate to the task being carried out . For example , employees handling an HPAPI with an OEL of < 1.0 µ g / m 3 may be required to wear a gown , double gloves and booties . For employees handling any material with OEL of ≥1.0 µ g / m 3 in the same plant , the standard PPE for entering the facility may not include any of these . In addition , specific tasks may require additional PPE ( i . e . gown or respirator ) based on chemical risk assessment . As previously indicated , HPAPIs with an OEL < 1.0 µ g / m 3 are typically manufactured in dedicated facilities . In addition to similar safety principles and standards , use of containment equipment might also be in place
in other facilities that handle APIs with higher OELs . After extensive air and swab monitoring , the containment capability in non-dedicated plants can be considered adequate to handle material with an OEL of < 1.0 µ g / m 3 . Thorough risk assessments should be completed to identify any potential opportunities for exposure and any upgrades that are needed to minimise personnel exposure . The ability to characterise material , in particular HPAPIs , is a critical aspect to developing robust crystallisation processes and understanding the processability of an HPAPI . This is particularly useful in drug product formulation . An extensive range of analytical tools should be available to support this type of work . Most of the required equipment ( e . g . SEM , DSC , TGA , PXRD , NMR , DVS , rheometer , specific surface area analyser ) can also be set up outside of an HPAPI laboratory environment . The outcome of a material handling risk assessment can lead to implementation of adequate controls to allow safe analysis of material with OEL < 1.0 µ g / m 3 outside an HPAPI laboratory .
Conclusion
Robust safety management of HPAPIs is paramount . This should be based on core principles from a well-defined banding system to a well-established SHE management system , supported by appropriate risk-management tools . A thorough risk assessment , supporting IH monitoring data , and continuous improvement in safe handling of HPAPIs can lead to increased manufacturing flexibility while maintaining adequate safety controls . •
Audrai O ’ Dwyer
GLOBAL MARKETING COMMUNICATIONS LEAD
SK PHARMTECO k + 353 1 8139227 J audrai . odwyer @ skpharmteco . com j www . skpharmteco . com
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