Charlie Johnson of Lonza looks at some of the key manufacturing challenges of HPAPIs
How CDMOs can help navigate containment challenges with HPAPIs
Charlie Johnson of Lonza looks at some of the key manufacturing challenges of HPAPIs
The high potencyof HPAPIs means they can cause harm if handled improperly . Consequently , they frequently have occupational exposure limits ( OELs ) of ≤ 10 µ g / m 3 of air as an eight-hour timeweighted average ( although there is no formally agreed-upon definition of an OEL level that constitutes a ‘ highly potent ’ compound ).
A rapidly growing category
Traditional classes of HPAPIs include hormonal compounds ( e . g . gonadotropin-releasing hormone agonists ), corticosteroids and certain biologics ( e . g . peptides , therapeutic proteins and enzymes ). Today , antibody-drug conjugates constitute a growing sub-category of HPAPIs , largely due to their utility as anticancer agents , though they also have potential in autoimmune conditions .
Currently , more than 1,000 highly potent small molecules are in development , with approximately 30 % targeting oncology indications , 20 % for autoimmune diseases , 20 % for diabetes and the remainder targeting other therapeutic areas . The HPAPI segment is growing at about a 10 % compound annual growth rate versus 6 % for the overall small molecule market . The segment is expected to double between 2018 and 2025 , from around € 16.65 billion to € 32.33 billion . 1 , 2
Meeting manufacturing challenges
Increasingly , small and emerging biopharma companies are driving the growth of the HPAPI category , particularly in the realm of speciality medicines , which often require
Lonza ’ s Centre for Excellence for HPAPI Development & Manufacturing in Visp
complex manufacturing processes under accelerated timelines . The synthetic route design of HPAPIs is critical as this determines when the molecule becomes highly potent , which in turn determines how much of the manufacturing has to be conducted using advanced containment engineering controls . Such early-stage challenges make it critical for HPAPI innovators to collaborate with a strategic partner with the capabilities to design , develop , and manufacture these increasingly complex molecules .
For companies lacking in-house HPAPI manufacturing capabilities , partnering with a CDMO is an essential part of any drug development strategy . The CDMO should have the requisite experience and wherewithal to meet the different challenges that arise throughout the commercialisation process . The optimal CDMO partner will consider both immediate and future production needs , and will support a range of potencies and containment through investment in flexible capabilities dedicated to
HPAPI manufacturing from early development to scale-up .
In a 2017 study , the Tufts Centre for the Study of Drug Development concluded that a single-source manufacturing model can shorten production timelines by 14 weeks and reap financial gains of up to € 41.4 million . 3 Outsourcing HPAPI production to CDMOs has increased significantly over the years , due to the inherently complex nature of HPAPIs that require specialised safety procedures , containment engineering , maintenance and training of personnel .
Prioritising safety
Although HPAPI-based drugs offer the possibility of substantial patient benefit , their manufacture presents numerous potential hazards such as carcinogenicity , mutagenicity and genotoxicity . These underscore the importance of a skilled operational workforce with experience in industrial hygiene and engineering .
A fundamental part of optimising HPAPI processes starts with a thorough understanding of the
16 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981