Dan Bowles , VP and general manager at Cambrex High Point , looks at the specific challenges of low-volume commercial API manufacture
Process development & manufacturing for oncologics & orphan drugs
Dan Bowles , VP and general manager at Cambrex High Point , looks at the specific challenges of low-volume commercial API manufacture
The API R & D and manufacturing landscape continues to undergo a significant transformation , particularly with respect to the development of oncologics and orphan drugs . These specialised therapies , often classified as higher potency compounds ( not necessarily true high potency APIs ( HPAPIs )), have unique challenges and development elements that call for advanced capabilities in process development and manufacturing .
This article delves into the evolution of these processes , focusing on higher potency handling , small-scale manufacturing considerations and the intricate requirements of producing these critical therapies , including the challenges of balancing a quality system designed for both early clinical and late-stage commercial APIs at one site .
The industry ’ s focus on oncologics and orphan drugs has grown aggressively over the last few years . Despite their limited market , orphan drugs are projected to generate $ 45 billion / year in sales by 2024 , 29-40 % of the total . 1 This trend underscores the importance of efficient manufacturing processes , tailored to the unique demands of these therapies .
Development elements & challenges
HPAPIs are a cornerstone in the development of oncologics and certain orphan drugs . They present unique challenges related to handling ; they often require specialised processing due to their potentially high toxicity and extraordinary efficacy at very low doses . This aspect often necessitates specialised facilities and equipment
to ensure worker safety and product quality .
The manufacturing of such compounds involves stringent containment measures to protect workers and prevent crosscontamination . Cambrex ' s approach to handling higher potency API includes the use of containment assets like isolators and closed-system handling and unloading , capable of manufacturing at a 1-10 µ g / m 3 occupational exposure limit ( OEL ) in traditional labs and production areas , and as low as 0.01 µ g / m 3 in dedicated OEB 5 specialised facilities .
Due to limited patient populations , API demand are scaled accordingly , meaning that the exponential growth in demand associated with more traditional blockbuster drugs will probably never be realised for orphan drug candidates . The production of orphan drugs and oncologics therefore requires specialised facilities or assets dedicated to small-scale manufacturing as a standard practice .
This presents unique challenges for drug developers , as traditional largescale CDMOs are generally eager to identify and implement programmes with potential for multi-tonne output . To address this gap in the market , Cambrex has completely overhauled its facility in High Point ( CHP ), North Carolina , to support small-volume commercial production . 2 As well as doubling clinical API manufacturing footprint , CHP has added three dedicated two-reactor commercial API suites featuring reactors ranging from 800L to 2,000L ( typical batch sizes 10-75 kg ).
The investment also included buildout of process chemistry , engineering and analytical laboratories designed to support all aspects of smallscale manufacturing . The additional footprint was designed with identical equipment to that used in the existing clinical suites , to reduce the risk of operational upset in moving from clinical to commercial batches . Since low-volume demand might generally
30 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981