As the field of oncology rapidly progresses, the world continues to recognize advancements in science that have led to a better understanding of the biology, immunology, and genetics of cancer. Just five years ago, The Nobel Prize in Physiology or Medicine was awarded to researchers for their discovery of cancer therapy by inhibition of negative immune regulation. These discoveries are translating to medical treatments at an unprecedented pace, sparked by a noticeable shift toward accelerated approvals and breakthrough designation status from regulatory authorities, as well as changes in the clinical development paradigm toward adaptive trial designs and combined phases.

Yet, as more of these potent and highly complex treatments are discovered, reducing development timelines while maintaining safety will be key to delivering critical oncology products to the patients who need them. Contract development and manufacturing organizations (CDMOs) must not allow the intricate requirements needed to produce, store and package these complex treatments hamper their success across the lifecycle chain. Instead, CDMOs must ensure that pharmaceutical manufacturing keeps pace by taking their own “laureate-like” approach to innovating in oncology.

Today, oncology is the fastest-growing sector of drug development representing 37% of the research and development pipeline.¹ This has led to the development of powerful specific targeted therapies, the majority of which are highly potent active pharmaceutical ingredients (HPAPIs), with highly potent drug products constituting the majority of the oncology pipeline.² With almost two million Americans diagnosed with cancer in 2022 alone, the increased demand for HPAPIs is exploding.

Interestingly, advances in oncology manufacturing that are innovating the way treatments are produced today are mirroring approaches spearheading drug discovery and treatment. These include the use of predictive models, next generation and digital technologies, robotics and analytics and artificial intelligence (AI). Just as these strategies have progressed the overall field, CDMOs and pharmaceutical manufacturers must remain vigilant on the innovations leading the pack on the development and manufacturing side. These innovations are upping the ante, transforming speed to market and safety of innovative oncology therapies.

Digital twins as predictive models

A recent Time Magazine headline hailed that scientists believe the future of medicine lies in creating digital twins, the replication of an object, process, or service in the virtual world. In oncology manufacturing, the innovation is here today, providing virtual replicas of the manufacturing process to reduce overall development timelines, ensure consistent product quality and support improvements in the manufacturing process. The “twin” serves as a predictive model, generating complex, real time information. Digital twins are also innovating the clinical trial process, where existing data is processed to create new, virtual patients. A digital twin can mirror elements of a clinical trial, as the resulting computer-generated “patient” can predict how the drug product will evolve over the course of the trial. While the sentient patient receives the treatment, the virtual one will have enough data and vitals to go through the trial via an AI-powered simulation. With the cost of discovering and developing therapies averaging around $1.3 billion and demanding 12-15 years to reach the market, digital twins are streamlining processes for small and large pharmaceutical organizations to get effective treatments to market.

Robotic sterile fill-finish to enhance safety and speed to market

In manufacturing, processing parameters and the container closure system differ between batches, forcing manufacturers to accommodate faster product changeover while protecting sterility. The potential for human error in fully decontaminating a production line can lead to failed batches, impacting a developer’s ability to deliver medications. In oncology, assuring the sterile preparation of the highly potent and intricate existing and future anticipated treatments that target specific forms of cancer is vital. That’s where the use of cutting-edge robotics becomes even more important. Robotic sterile fill-finish technology is delivering flexible aseptic fill-finish solutions for both small- and larger-scale production runs across a variety of dosage forms including vials, prefilled syringes, and cartridges for use in auto-injectors. Robotics not only ensure an uncontaminated product but also increase capacity, accelerating time to approval and reducing the critical time to clinical and commercial launch of treatments.

Artificial intelligence, technologies revolutionizing the industry

While real world adoption of AI in healthcare overall has been slow, the use of AI in drug discovery has increased by over 40% annually across the industry. Most manufacturing companies have been digitalizing laboratories and using AI and machine learning in conjunction with robotics to enable real-time release testing. The result? A significant reduction in the complexity and time of manufacturing and testing by constantly providing feedback on any potential errors.

Other emerging technologies and approaches are at the forefront of oncology manufacturing including automated microdosing technology to deliver high potent drugs directly into capsules. By filling “neat” HPAPIs directly into capsules, we can potentially provide the fastest option for candidates entering early phase clinical trials. Microdosing ensures exceptional levels of accuracy and precision while minimizing wastage of drug substance. The result is a reduction in time and financial investment at the earlier stages of drug development, minimizing the use of often costly active pharmaceutical ingredients, and the associated formulation and analytical development required to support an Investigation New Drug application or Investigational Medicinal Product Dossier. With microdosing, the timescale to early phase clinical manufacturing can be reduced by as much as 50% between four and six months and lead to an overall cost reduction of around 70%, depending on the cost of HPAPIs.

Process analytical technology, or PAT, is another growing technology that is particularly beneficial to improving high potent drug manufacturing we see in oncology. PAT is a system for designing, analyzing, and controlling manufacturing through real time measurements of critical quality and performance attributes of raw materials, in-process materials, and processes with the goal of ensuring consistent final product quality.

Near Infrared (NIR) Spectroscopy, is a non-destructive tool that can be used to determine when a high potent blend is uniform without sampling and analytical testing. This technique can also be utilized during granulation and fluid bed drying end point determination. NIR does however have some limitations and challenges due to sensitivity with very low concentration blends, that are often seen using HPAPIs in oncology product development. Laser Induced Fluorescence is a lesser used PAT tool that can provide improved sensitivity, increased limit of detection, better signal to noise ratio for certain APIs compared to NIR and other analytical measurements and is being used successfully at PCI to optimize process development pathways.

The growing need for new and effective oncology treatments is astounding. As biopharmaceutical companies discover transformative molecules/candidates, we as development and manufacturing partners must accept the challenge and responsibility to drive and leverage innovations that meet the unique requirements of these complex treatments. Only then can we ensure their safe and expeditious delivery to patients. Many times, these innovations are as cutting edge as the discoveries themselves and they are expanding every day, as the oncology market increases.

I believe Nobel laureates James P. Allison and Tasuku Honjo (yes, the immunologists) would be proud of our achievements on the development and manufacturing side and what’s to come. In the fight against cancer, we need to aim as high as they have. 

References

1. www.iqvia.com/insights/the-iqvia-institute/reports/global-trends-in-r-and-d-2023
2. www.grandviewresearch.com/industry-analysis/high-potency-active-pharmaceutical-ingredients-hpapi-market

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Rebecca Coutts, Ph.D., is the General Manager of PCI Pharma Services’ award-winning, state-of-the-art center of excellence for potent manufacturing in Tredegar, Wales. She has over 25 years of experience across the pharmaceutical development industry, including previously serving as the Director of Development and Associate Director of Contained Manufacturing at the Tredegar site, specializing in the latest containment technologies and processing of highly potent molecules. She received her bachelor’s degree in pharmacy before completing a Ph.D. in pharmaceutics at Cardiff University.