SPECIAL ROUNDTABLE - Which Trends Will Have the Most Impact on Drug Development in 2022?

By: Cindy H. Dubin, Contributor

Drug Development & Delivery posed this question to life science leaders during a recent roundtable discussion. While their responses are varied, a common theme is that COVID-19 has left a lasting impact on the industry, from finding skilled labor to a resurrection of vaccine development to shaping relationships between drug manufacturers and outsource providers. Other trends anticipated this year include antibody drug conjugates development, an increased use of advanced digital manufacturing and analytical technologies, and a greater path forward for cell and gene therapies.

“Supply chain shortages will be a prominent challenge well into 2023.”

Manufacturers have seen supply chain disruptions, a drastic change in the workplace, and an impact on the availability of skilled labor due to the COVID-19 pandemic. These are challenges we can expect to continue moving into 2022. But, supply chain shortages will likely have the biggest impact, with some single-use equipment, including bioreactor bags, already having lead times of up to 12 months.¹ This is an even greater challenge for companies expanding facilities to meet the increased demand for COVID-19-related product manufacturing capacity. Companies with multiple manufacturing platforms will need to increase inventory to mitigate the potential disastrous impact of supply delays. This must be balanced with ensuring adequate support for supply chain management and available warehouse space to store stock. At Genezen, careful planning and management has minimized the impact of potential delays, allowing us to scale on schedule in our new multi-vector production facility. In these turbulent times biopharma manufacturers find themselves in, there is no way to predict what the production schedule will look like a year from now. However, it is safe to say that supply chain shortages will be a prominent challenge faced by the biopharma industry throughout 2022 and likely into 2023.

“There is a growing focus on mRNA therapies in development.”

We will see increasing and sustained demand for development, manufacturing, and fill-finish services for injectables from the biotech industry. The global injectables market is set to grow at a CAGR of 10.95% from 2021-2025 when it’s estimated to reach $759.61 billion.²

There is also a need for more flexible, niche, and smaller batch capabilities. This is being driven by the focus on developing treatments for orphan diseases and personalized therapies and has been accelerated by a growing focus on mRNA therapies in development, catapulted by the successes of COVID-19 vaccines. The continued prioritization of oncology in the drug development pipeline will drive much of this growth for the coming years.

There are also a lot of innovative new players entering the pharma and biotech space. In 2001, there were just over one thousand companies with active R&D pipelines across pharma and biotech. In 2020, this figure climbed to over 5,000.³

As a growing proportion of investigational therapies sponsored by smaller and/or virtual pharma companies progress through pre-clinical phases and prepare for trial, they will often lack the experience or capacity to manufacture their product at any scale, which leads to a greater rate of outsourcing.

Finally, companies are likely to see greater demand for capacity domestically as pharma and biotech look to reshoring to create more resilience in supply chains after the pandemic exposed the frailties associated with global networks. The Biden Administration has already directly invested in domestic production of COVID-19 drugs. The Biomedical Advanced Research & Development Authority (BARDA) signed a deal with Phlow Corporation to produce essential medications at Virginia Commonwealth University’s Medicines for All Institute, but greater governmental support will likely be needed if reshoring is to be a long-term strategy.

“Versatile HPMC will facilitate capsule-based oral solid dosage.”

There were 17 million new cancer cases and 9.5 million cancer deaths worldwide in 2018, according to the International Agency for Research on Cancer (IARC) and the global burden of this disease is only expected to grow. It’s no surprise that the industry’s focus on this disease will continue to trend.

Many oncology drugs use highly potent APIs (HPAPIs), and innovators, as well as their contract development partners, are seeing an increase in the number of global development projects involving HPAPIs as pharma companies continue to develop innovative treatments at a rapid pace. Many of these compounds are poorly water soluble and require precise excipient strategies and formulation approaches. One excipient proving effective in improving the bioavailability of poorly soluble compounds is hydroxypropyl methylcellulose (HPMC). The need to deliver the potent poorly soluble APIs now under development is contributing to a shift towards encapsulating these formulations in HPMC to help extend the excipient’s effect. Studies conducted by Lonza Capsules and Health Ingredients have shown HPMC capsules deliver consistent disintegration and dissolution properties, which helps optimize therapeutic effect and dose performance. Moreover, gelatin-free HPMC capsules are suitable for moisture-sensitive ingredients, provide product stability, and avoid the risk of cross-linking. Because of HPMC’s versatility and compatibility, capsule-based oral solid dosage will continue to trend in 2022 as well.

“The move towards mRNA-based technologies will pave the way for cell and gene therapies.”

The COVID-19 pandemic saw the dramatic increase in investment and accelerated expansion of mRNA-based technologies. The use of mRNA vaccines highlighted their massive potential, and subsequently led to it becoming the technology of choice for COVID-19 vaccine developers. However, its popularity is not limited to only the COVID-19 market. Its flexibility and effectiveness have made it an attractive option for the treatment and prevention of many other diseases, ranging from cancers to HIV. As of July 2021, there were more than 70 mRNA therapeutics in clinical pipelines globally and many more assets in early development.⁴

Despite the difficulties associated with supporting the manufacturing of this relatively new and unfamiliar technology, some CDMOs rose to the challenge and embraced the learning curve. They balanced the needs of these new projects with those ongoing by expanding their facilities and capabilities. As a result, these CDMOs are now better placed than ever to support emerging technologies, including cell and gene therapies (C&GTs). Their experience pivoting to accommodate new processes and optimize them will go hand in hand with their increased capacity to smoothly scale C&GT manufacturing and development to commercial sizes in future.

“Macro-level challenges seen over recent years are likely to become increasingly overt.”

Life science demand is at an all-time high, fueled by a strong continuation of capital investment from public and private investors and advances in product technologies. The set of tools at our disposal in medical treatment remains ever-growing, with annual progress in protein therapeutics and expansion of cell- and viral-derived products. Particularly notable progress has been made in AAV gene therapy, CAR-T cell therapy, gene-editing technology, mRNA therapeutics, vaccines, and oncolytic viruses. Consequently, the industry now finds itself progressing rapidly in this golden age period.

Macro-level challenges seen over recent years are likely to become increasingly overt. Focal points include growth and access to highly specialized labor and improvements to workforce training programs. In the currently saturated markets, stabilizing raw material and equipment demand, and furthering availability of accessible and affordable lab and cGMP plant production capacity, are especially challenging.

Industry recognizes the need to adapt, work in unfamiliar yet innovative ways, and consider evolving its approach for tomorrow. With many advances on the horizon, focusing on the foundational aspects to support continued growth is key. Macro-level challenges will drive positive pressure from the strong sector-wide growth, creating opportunities for breakthrough and accelerated progress with ingenuity and creativity.

“The next era will belong to ADCs.”

While antibodies continue to generate effective drug products, it’s safe to say that the next era will belong to antibody drug conjugates (ADCs) as seen by the increasing pace of approvals and the growing activity in major investments and transactions across biotech and Big Pharma. Aligned with this is the simultaneous innovation and development of new technologies and payloads that are improving the effectiveness and safety profile of this “magic bullet” drug strategy. The building momentum in successful ADC developments has encouraged progress in exploring more innovative design and application of bioconjugate drugs. Development of new carrier molecules, linker motifs, and cargos have opened the potential to move beyond the classical delivery of toxins to cancer cells and deliver therapeutic molecules to disease tissue in other therapeutic indications. So, while cancer indications still top development pipelines across the ADC field, very successful progress is being made in other areas such as muscular dystrophy where novel bioconjugates are used to address the genetic basis of disease. The delivery of the promise of ADCs makes for a very exciting period for drug development and positive outcomes for human health.

However, we can’t ignore the fact that COVID has ‘resurrected’ scientific, development, and investment interest in vaccines – an area that has not been at the cut and thrust of drug development for some time. The impact of RNA vaccines has profoundly demonstrated how valuable vaccines are to protecting human health and, as it happens, the global economy. Having the RNA technology validated so successfully has rightly prompted increased interest in how and where we can develop and apply vaccine strategies. However, the industry needs to be a little bit cautious and use lessons learned from COVID to advance vaccine potential, and not forget tried and failed vaccines attempts (cancer) or suboptimal paradigms (influenza). Investment interest will likely focus on technologies to promote broader (antibody and cell-mediated cross-reactive immune responses) and long-term, cold-chain friendly formulations. Towards this, it is encouraging to see the collaborations that are developing across the industry, including the recent partnership announcement between BioNTech and Crescendo. Finally, while regulators have adapted in the past to support a more rapid, patient-benefit-focused approval process (e.g. checkpoint inhibitors), the experience and success with COVID have created a real opportunity to review and consider innovative changes. Consequently, we may see changes that allow a more practical approach driven by drug type and precedence (similarity to other tested drugs), and context (urgency and level of population risk).

“Implement advanced digital manufacturing and analytical technologies.”

In response to COVID-related supply disruptions, the industry faced a drastic realignment of their business priorities. The pandemic forced everyone’s attention to attaining better operational risk profiles and many companies redoubled their efforts to implement the digital technologies and analytical tools needed to stabilize strained supply chains. The digital disruption of the industry is a recurring theme in pharma and is continuing to prompt systemic change – the kind the industry’s operational managers will likely wrestle with well beyond 2022. What is troubling is, that in retrospect, the impact on operations and supply chains during the pandemic were the result of the same chronic supply chain disruptions that have been plaguing pharma’s supply chains for years. In some ways it feels as if the industry is stuck in a time warp – it’s a new year, and while the industry’s learned some important lessons, 2022 is beginning to feel a lot like 2018. If pharma is to break out of this loop, many long-standing assumptions will have to be re-examined – including the uptake and implementation of advanced digital manufacturing and analytical technologies – the sort of connected, collaborative tools the CDMO industry needs to accomplish increasingly faster development timelines and stable supply continuity the world is demanding post-COVID.

“There will be increased demand for scalable packaging and cold chain handling of biologics.”

Emerging technologies and the continual shifting in development pipelines, combined with more approvals for novel complex biopharmaceuticals, are testing the industry’s packaging partners – the packing, storing, and transporting of pharmaceutical products is more sophisticated than ever. The increasing sensitivity of biologic drugs is heightening demand for specialist parenteral filling and packaging capabilities at various scales and increased cold chain capacities. Many biopharma treatments rely on parenteral delivery. As such, the success of biotech development necessarily drives the growth of injectables. The global injectable market is projected to almost treble in value by 2027 when compared to 2019, reaching an estimated $1,251.28 billion.⁵

By 2024, the market for products requiring refrigerated storage and transportation is estimated to increase by up to 48%, with cold chain products growing at almost twice the rate of non-cold chain.⁶

It’s inevitable that the contract industry will invest heavily in existing facilities and M&A activity will increase as companies seek to ensure they can service this demand. The industry’s pandemic response – developing and commercializing numerous vaccines incredibly quickly and at scale – will have created some of this capacity but, as it stands, the need for COVID-19 vaccines will continue for some time and further investment will be needed.

Additionally, the patient experience and usability have become key considerations for injectable drug developers. Patients increasingly want to administer drugs themselves away from clinical environments, but this needs to be as simple as possible to ensure they take their treatment at the right frequency and dose to maximize compliance and, therefore, efficacy. A lot of time and resource has been devoted to developing delivery systems that support easier self-administration of injections at home, including guards to prevent needle-stick injuries and finger flange devices to simplify one-hand injection. Prefilled syringes (PFS) are a key figure in the discussion as they are arguably the simplest form to administer.

For manufacturers and their partners, PFS products have highly complex requirements when it comes to processing, handling, and packaging; they also often have a higher number of components that need to be included in final kits. As the biologics sector grows, and PFS formats become more sought after, careful planning is required to ensure a product can be sufficiently scaled in its existing packaging – this will be a key trend that shapes a lot the relationships between manufacturers and contract packaging partners in the coming years.

“Lipid Nanoparticles will facilitate patient-centric drug development.”

One trend that will become increasingly important is the use of nanotechnology. The global nano-pharmaceutical drugs market, brought to the fore for many as the successful delivery platform of COVID-19 vaccine carriers, is poised to reach more than $80 billion by 2027.⁷

The demand for novel Lipid Nanoparticles (LNPs) to support the delivery of oligonucleotide and nucleic acid-based therapies, not just for vaccines but also in immuno-oncology, is growing at an exponential rate. And while there are key questions on formulation, process development, and scalability that still need to be answered, the versatility of nanoparticles as a drug delivery technology platform, their ability to transport hydrophobic/hydrophilic molecules, small molecules, proteins, oligonucleotides, and their use in antitumor formulations means there has been robust growth in patent filings and published papers targeting LNPs. Lipid Nanoparticles have an even stronger future as carriers in genetic medicines with special designs in accordance with patient-centric drug development. Further improvement of mRNA LNPs through RNA sequence engineering, design of lipids, and modification of lipid structure will allow organ-specific delivery. Next-generation LNPs will facilitate more mRNA-based therapies in the future, which is why they are an area of increasing importance for the industry.

References
1. Single-use lead times up to 12 months as COVID takes its toll, Dan Stanton, BioProcess Intl., May 3, 2021. https://bioprocessintl.com/bioprocess-insider/upstream-downstream-processing/single-use-lead-times-up-to-12-months-as-covid-takes-its-toll/.
2. Global Injectables Market (2021 to 2025) – Insights & Forecast with Potential Impact of COVID-19, Research and Markets, June 28, 2021,https:// www.globenewswire.com/news release/2021/06/28/ 2253632/28124/en/Global-Injectables-Market-2021-to-2025-Insights-Forecast-with-Potential-Impact-of-COVID-19.html.
3. Total number of pharmaceutical companies with active R&D pipelines worldwide from 2001 to 2021, Matej Mikulic, Statista, May 20, 2021, https://www.statista.com/statistics/791340/pharmaceutical-companies-number-with-active-pipeline/.
4. Number of mRNA therapeutics in clinical pipelines worldwide as of July 2021, by therapy area, Matej Mikulic, Statista, Nov. 8, 2021, https://www.statista.com/statistics/1262846/clinical-pipeline-of-mrna-therapeutics-by-therapy-area-worldwide/.
5. The Worldwide Injectables Industry is Estimated to Reach $759+ Billion in 2025 at a CAGR of 10.95% from 2021, Research and Markets, June 25, 2021, https://www.businesswire.com/news/home/20210625005358/en/The-Worldwide-Injectables-Industry-is-Estimated-to-Reach-759-Billion-in-2025-at-a-CAGR-of-10.95-from-2021—ResearchAndMarkets.com.
6. 2020 pharma Cold Chain Sourcebook forecasts a $17.2-billion logistics market, Pharmaceutical Commerce, April 27, 2020, https://www.pharmaceuticalcommerce.com/view/2020-biopharma-cold-chain-sourcebook-forecasts-a-17-2-billion-logistics-market.
7. Nanopharmaceutical Drugs Market Size To Be Worth USD 82.71 Billion by 2027 Growing at a CAGR of 7.3%, Emergen Research, December 21, 2020, https://www.globenewswire.com/newsrelease/2020/12/22/2149060/0/en/Nanopharmaceutical-Drugs-Market-Size-To-Be-Worth-USD-82-71-Billion-by-2027-Growing-at-a-CAGR-of-7-3-Emergen-Research.html.