Speciality Chemicals Magazine JUL / AUG 2024 | Page 17

HIGH POTENCY APIS toxicological properties of the HPAPI itself and also its intermediates . This enables a detailed risk analysis that combines the inherent hazard of the materials with exposure potential and subsequently the definition of unit operations with the necessary containment strategies , particularly those involving solid charging , sampling and unloading of the HPAPI and potent intermediates .

Manufacturers aim to minimise the number of transfer steps for highly potent molecules , and to optimise safety and efficiency by using as little equipment as possible .

STOPping hazards

By necessity , CDMOs employ stringent , well-designed protection strategies that incorporate nuanced and detailed processes for workers to use and clean HPAPI manufacturing assets . Often these strategies reflect a hierarchy of protective measures as defined by the STOP principle : Substitution ( i . e . elimination of risk ), Technical protective measures , Organisational protective measures and Personal protective measures .

Typically , adherence to the STOP principle entails implementing cleaning procedures that include clear acceptance criteria for opening equipment after pre-cleaning . Another key protective measure is embedding safe equipment start-up sequences into risk assessment processes , stipulating leak testing and rinsing prior to production , and defining criteria allowed for production release .

Personal protective equipment ( PPE ), including coveralls , boots , gloves , chemical suits and supplied air , is extremely important for keeping workers safe and should be available to anyone working with highly potent materials . However , PPE should be considered a last resort , not the main method of protection for routine operations .

Importantly , adherence to a welldesigned containment strategy requires a well-trained workforce with a strong commitment to a culture of safety . The most reputable CDMOs are led by executives who actively cultivate a robust safety mindset throughout the organisation . With comprehensive training programmes that brook no deviations in compliance and a culture encouraging the free flow of safety-enhancing ideas from employees and managers , these CDMOs exemplify a focus on enhancing the motivation and dedication of their staff members .

Riding the outsourcing wave

In response to the growing demand for safe , sophisticated and streamlined HPAPI manufacturing and containment , some CDMOs are investing significantly in facilities dedicated to HPAPI development from preclinical through commercial production . With their emphasis on safe procedures from equipment start-up to handling , cleaning , and decontamination , these organisations are well positioned to leverage the rapidly increasing pace of outsourced HPAPI production .

For example , Lonza ’ s Centre of Excellence for HPAPI Development & Manufacturing at Visp , Switzerland , offers a comprehensive platform supported by an experienced team that works to mitigate safety risks when working with highly potent substances . The centre also features extensive evaluation and training procedures , along with advanced facilities .

Those assets enable the safe handling of HPAPI molecules at exposure levels up to 100 ng / m 3 across all manufacturing scales ( up to 10 m 3 ), allowing production to scale upward or downward flexibly as needed . For more potent compounds , such as ADC payloads that require containment down to 1 ng / m 3 , the Visp site has separate and segregated capabilities , allowing for the safe handling of compound quantities ranging from grams to multiple kilograms .

Additionally , Lonza ’ s site in Nansha , China , features a dedicated HPAPI manufacturing line that includes three 1,000L GMP trains , along with new development and GMP laboratories capable of manufacturing small batches of HPAPIs . This allows for mid-scale manufacturing to ensure a smooth transition between earlyphase and commercial production .

Outlook

Over the next several years , the need for more targeted treatments in the oncology and autoimmune sectors will likely drive increasing demand for HPAPI molecules . To meet that demand , biopharma companies will need access to flexible and sophisticated manufacturing capabilities in order to deliver their innovative products to patients . That need , in turn , will require continued vigilance from manufacturers – including CDMOs – in adhering to stringent protocols for handling highly potent substances .

Given the expected demand , CDMOs will need to continue to invest in dedicated HPAPI suites and other assets to control containment and help ensure the safe management of these substances throughout all stages of development . Biopharma innovators , for their part , should base their outsourcing strategies on choosing a CDMO with a demonstrated track record in the HPAPI space , supported by robust containment , handling , and manufacturing capabilities . Such careful planning and consideration will help ensure the continuous supply of highly potent therapeutic substances to meet patients ’ needs . ●

Charlie Johnson

SENIOR DIRECTOR

JUL / AUG 2024 SPECCHEMONLINE . COM

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