Dr Jean-Francois Carniaux , VP and global API technical lead at Piramal Pharma Solutions , looks at what CDMOs must offer in the manufacture of HPAPIs
HPAPIs & the need for wellcontained chemistry
Dr Jean-Francois Carniaux , VP and global API technical lead at Piramal Pharma Solutions , looks at what CDMOs must offer in the manufacture of HPAPIs
HPAPIs continue to be a rapidly growing segment of the pharmaceutical industry . This is due to an increased focus on targeted therapeutics in disease areas such as cancer . Industry reports state that the global HPAPI market in terms of revenue was $ 23.2 billion in 2021 and it is expected to reach $ 38.2 billion by 2027 .
The growth in antibody-drug conjugates ( ADCs ) boost that forecast even further . They are becoming a greater contributor to the HPAPI market because their core active component , the payload , is typically classified as an HPAPI . ADCs are projected to grow from $ 240 million in 2022 to $ 538 million by 2030.1 This is reflected in an additional 220 clinical phase I and II programmes and about 900 discovery or preclinical programmes . 2
What CDMOs must offer
Any company looking to take part in the manufacture or the contracting of such HPAPIs must be prepared to , or understand the requirement to , handle these potent compounds safely . These include having the appropriate facilities , procedures , controls and expertise in-house to guarantee the safety of all personnel involved in the manufacturing , analysis and handling required to produce HPAPIs .
In many cases , pharmaceutical organisations rely on CDMO partners that possess both the capabilities and expertise to successfully — and safely — bring these drugs to market . Piramal Pharma Solutions is one such company , having launched several blockbuster oncology drugs over the past four decades at its site in Riverview , Michigan .
The company also now offers payload manufacture based on auristatin and camptothecin from this site . These payloads are conjugated to an antibody at its ADC site in Grangemouth , UK . ADCs are then formulated at its fill / finish facility in Sellersville , Pennsylvania .
Banding challenges
There are some unique challenges associated with manufacturing HPAPIs , specifically due to their high potency and toxicity . To determine which containment strategies need to
be put in place in a facility to properly handle a compound , a manufacturer must first determine the API ’ s potency category to determine the needs to be associated with its handling .
Together , the toxicology , safety and engineering departments must determine the compound ’ s level of potency and the exposure limit , or the range the facility must keep the level below to maintain the safety of employees ( i . e ., an occupational exposure limit ( OEL ). This is measured in units of mass per unit volume of air .
Occupational exposure bands ( OEBs ) are an alternative means to categorise the exposure limits for APIs or other compounds that do not have an established OEL and associate these categories to the use of containment methodology and personal protective equipment that are recommended to limit exposure to compounds to the range of each band .
There is no single industry standard banding system , but many companies have developed internal procedures and associated containment needs for Bands 5-6 as shown in Figure 1 . The growing number of pharmaceutical companies entering the ADC field
18 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981