EPM speaks to Swiss contract development manufacturing organisation (CDMO) Lonza to learn about the advances taking place across the industry to manufacture high potency active pharmaceutical ingredients (HPAPIs).
EPM: What are some of the emerging trends we’re seeing right now in the HPAPI market?
RL: We see a direct relationship between the continued validation of precision medicine approaches and the growth of high potency APIs (HPAPIs) in the development pipeline and in regulatory approvals. Medicinal chemists have become extremely efficient at innovating exquisitely targeted protein modulators with impressive binding affinities. Precise delivery mechanisms and bioavailability enhancing technologies are enabling HPAPIs to create a pipeline of more effective medicines, with potentially lower dose requirements and fewer side effects.
Interest in highly potent drugs is largely driven by oncology research and more targeted therapies across a number of indications. Currently, over 1,000 highly potent small molecules are in development, with approximately 30% targeting oncology, 20% for antidiabetics, 20% for autoimmune diseases and the remainder for other indications.
Due to their wide range of potential uses and benefits for patients, the growth in the HPAPI market is outpacing the overall API market by almost two-to-one. The segment is growing at about 10% compound annual growth rate, compared to 6% for the overall small molecule market. The market value from existing and new HPAPI product launches is expected to double between 2018 and 2025, from around $18 billion to $35 billion.
EPM: How have CDMOs adapted to be able to manufacture HPAPI products?
RL: In response to the growing need for sophisticated HPAPI manufacturing, some CDMOs are building flexible, integrated capabilities dedicated to HPAPI development from preclinical to commercial production. These programmes place an emphasis on safe procedures from equipment start-up to handling, cleaning and decontamination, and they come as outsourcing of HPAPI production is increasing at a rapid pace. Demand for highly potent small molecule API manufacturing and development services is keeping pace with the overall HPAPI market value, and is expected to exceed $7.5 billion by 2023, more than doubling the $3.5 billion market size in 2015.
For biopharma innovators, working with a single partner across the development pipeline can shorten timelines and reduce risk. CDMO partners can access in-house experts across a range of drug substance and drug product challenges, engage in technology transfer activities and exchange information, ideas and best practices across the drug development cycle. A study from Tufts Center for the Study of Drug Development has found that asingle-source outsourcing model can shorten the drug development cycle by 14 weeks and lead to financial gains of up to $45 million. For HPAPI compounds, drug product capabilities will include parenteral formulations / sterile fill-finish services and oral delivery options such as liquid-filled hard capsule technology. Contained particle engineering can also be required for safe and effective jet milling or spray dry processing. Outsourcing development to a qualified CDMO can help meet accelerated production timelines and help deliver life-saving therapies more quickly to patients who need them.
EPM: What are some of the best practices in terms of containment and handling when it comes to HPAPIs?
CR: This trend towards greater use of HPAPI molecules presents significant potential benefits for patients, but it also comes with handling, containment and manufacturing challenges for innovators and their development partners, since these molecules can be dangerous if mishandled. Safe HPAPI handling can be ensured by focusing on facility design, protection strategy & procedures and personal protective equipment.
Sophisticated facility design elements include several tools to ensure safe handling of potent materials. Units are available for primary and secondary containment of the entire process including solid charging containment, sampling and unloading. For product sampling, liner ports can help lock in and lock out glass sampling bottles. To aid in the product unloading process, manufacturers can use endless liner systems and customised flex isolators (in some cases more rigid, hard-walled isolators may be preferred).
Well-designed protection strategies include nuanced and detailed processes for how workers can use and clean HPAPI manufacturing assets. For example, cleaning procedures should include clear acceptance criteria for opening equipment after precleaning. And the safest equipment start-up sequences are embedded into the risk assessment process, with leak test and rinse prior to production and defined criteria allowing for production release.
Personal protective equipment (PPE) is of course extremely important to keep workers safe. Reliable equipment including coveralls, speciality hoods and isolators, gloves, chemical suits, supplied air (if appropriate) and other implements should be available in ample supply for anyone working with highly potent materials. However, the use of PPE should be the last resort and not the main method of protection for routine operations. Adequate organisational measures and procedures can often accommodate PPE-free operations, keeping the PPE only for non-routine operations.
EPM: What’s next for HPAPI drug products in terms of the future?
CR: As HPAPI molecules continue to play a growing role in new pharmaceutical products, biopharma companies will need access to flexible, sophisticated manufacturing assets to bring their innovative products to market and to patients. Given the high potency of these molecules, safety and containment are key components of effective HPAPI manufacturing. Working with a qualified CDMO can help biopharma companies advance HPAPI compounds and products at high speed and low risk. When evaluating external partners, biopharma innovators should base their choice on the CDMO’s experience in the HPAPI space and thecontainment, handling and manufacturing assets the partner brings to bear.
EPM: With the rise of specialised medicines is there enough manufacturing expertise to match demand from the biotech sector?
RL: Close communication and alignment between customers and the CDMO industry are required to ensure that the appropriate manufacturing expertise is built and put into place when it is needed. The CDMO industry will have to listen to its customers’ needs and ideally be involved from the very early stages of the product life cycle in a close and collaborative manner. In terms of nurturing talent and expertise in CDMOs, at Lonza our people are a core part of our strategy. We focus on keeping our expertise in-house and have defined action plans that further develop critical skillsets. We commit ourselves to improving the customer experience through an engaged workforce and continue to be strategic in attracting strong talent.