Complexity, Speed and Cost Pressures: As Medicine Changes, So Does AstraZeneca's Approach

The world around us is rapidly changing. At AstraZeneca, one of the largest international biopharmaceutical companies, we have a responsibility to patients and society to help build a healthier world. We are evolving our business with our Growth through Innovation strategy to ensure that we are able to design, develop and deliver our portfolio of medicines using innovative platforms and ways of working.

Our global operations team has a significant role to play to scale for the patients with speed, quality and sustainability, using technical and digital innovation and engaging a talented workforce. While we continue to see external and internal shifts in demand for our medicines, we have proactively identified several ways to address these changes and develop the strategies that ensure our manufacturing network is fit for the future.

The Changing Healthcare Landscape

Global trends continue to increase the demand for healthcare, and breakthroughs in technology are helping improve health outcomes. The COVID-19 pandemic has highlighted challenges and accelerated healthcare innovation and change. As the world’s population grows and life expectancy increases, so do the incidence of non-communicable diseases and the volume of medicines to treat or manage the global disease burden. Data management in healthcare is moving beyond storing data to focusing on extracting insights on population health management and value-based care to improve health outcomes and personalised healthcare. Innovations in technology are allowing people to receive their medicines at home, monitor and collect their own health data and become active participants in managing their healthcare.

These global healthcare trends are further increasing the complexity, speed and cost pressures we must respond to while still navigating a highly regulated environment. Meanwhile, we are facing internal pressures to adapt as well. Our pipeline is evaluating the next generation of therapeutics and we are investigating new categories of medicines that have not been explored before—and we must find new ways to formulate those molecules into medicines and manufacture those medicines with new technologies. Therefore, innovation is critical. We must drive implementation of digital transformation and embrace innovative manufacturing technologies that will reduce lead time, environmental impact and increase agility.

Adapting our Development and Delivery of Medicines

New modalities, which are non-traditional molecules with therapeutic effects, are an emerging and complex category of medicines that represent about 30% of our company’s pipeline. They present a promising opportunity to treat a variety of diseases. However, the commercialization of new modalities is limited by:

• High cost—greater than 10 times the price of gold per kilo to produce
• High waste—each kilogram of product creates at least 5 tons of waste
• Small manufacturing scale—manufacturing plants that can produce required commercial volumes do not yet exist

There is also increasing demand for manufacturing combination medicines, creating a need to develop patient-centric solutions, including devices that are both sustainable and enabled digitally to provide connectivity. This requires different capabilities than established for more conventional medicines. And in order for these new and promising medicines to reach patients, chemists and chemical engineers must develop new processes to manufacture these medicines at a greater scale.

A critical method for delivering more medicines to more patients more quickly is through a shift from batch manufacturing to continuous manufacturing. It is widely recognized throughout the pharmaceutical industry that continuous manufacturing is fundamental to achieving supply of products over the next five to 10 years. Three of the main benefits are agility of supply, easier scale-up and reduced factory footprint.

Within AstraZeneca, this opportunity is being realized through a strategic manufacturing platform switch that allows us to move from traditional batch manufacture to continuous manufacturing using continuous synthesis steps and direct compression as integrated platforms[1]. Our focus will be to develop and launch new chemical entities on the continuous manufacturing platforms, and, when appropriate, switch specifically identified in-line medicines.

Indicative assessments show that for a single product line with one billion tablets annually, continuous direct compression could deliver a reduced machine run time of more than 5,000 hours per year and achieve millions of dollars in savings while delivering the expected quality more reliably.

In addition to driving productivity, we can eliminate some of the day-to-day barriers we experience with the traditional batch manufacturing method. For example, fixed batch size limits our flexibility after a medicine is launched and the process is reliant on end-product testing. With continuous manufacturing, we can use identical equipment for clinical and commercial production. This means we will see greater flexibility on batch size, enhanced control strategies and real-time release of products. Embracing this new way of working through the product lifecycle is already proving successful at several of our major manufacturing sites worldwide.

(Continuous synthesis steps involve running a single chemical transformation using a continuous flow chemistry approach, accounting for the multiple steps needed to produce an active pharmaceutical ingredient. Direct compression is a standard formulation technology for the production of oral solid dose—tablet—medicines. Traditionally, this production step is conducted separately.)

Embracing new technologies is critical as we recognise that smart digital approaches are revolutionizing real-time process measurement and control, and the need for scale-up is totally removed, facilitating faster development. For the development of active pharmaceutical ingredients, the “plug and play” modular technologies enable multi-step flow chemistry, which means that we can quickly set up and embed new systems where we need to connect different modules together. This will shorten supply lead times. It will also enable the adoption of more atom-scale green chemistry by designing the equipment to fit the optimal chemistry, versus the current approach in which chemistry is designed to fit the equipment.

Unsurprisingly, the true game changer lies in our ability to leverage digital and data—specifically applying them to commercial manufacturing in design and development of future processes. Higher computing power is enabling more complex, real models that demonstrate a higher level of product and process understanding. Increasing our predictive capability will enable faster process development. Ultimately, models and AI could be used to control our processes real time, adjusting critical process parameters to maintain systems in a controlled state and deliver “Golden Batch” performance, repeatedly eliminating deviations and waste. The opportunities are becoming a reality.

We know that moving forward, the landscape will change and demand will increase for new and more medicines. By anticipating these changes and initiating transformation now, we can be in a better position to meet the future needs of patients. It’s an exciting time to follow the science and embrace digital and technological innovation for the development, manufacture and supply of future medicines.

Dafni Bika is the SVP and Global Head of Pharmaceutical Technology and Development at AstraZeneca. She leads a global network in eight countries and 16 locations of more than 1,200 innovative science and technology professionals who design, develop and commercialise new medicines and provide continuous improvement across the product life cycle. She holds a Ph.D. in Materials Science and Engineering from the University of Pennsylvania.