What Trends And Innovations Are Biopharma Manufacturing Execs Watching?

By Rob Wright, Chief Editor, Life Science Leader
Follow Me On Twitter @RfwrightLSL

The best idea means nothing if you don’t have the ability to manufacture at the necessary scale. Throughout the pandemic, we’ve witnessed a wide variety of manufacturers struggle to produce an adequate supply of just about everything, from toilet paper and food to microchips and automobiles. And while shortages can be a financial inconvenience for many companies, in the world of biopharma it could mean the difference between life and death. So, in putting together our annual outlook issue, we asked a number of manufacturing executives what innovations and trends they are paying attention to as we enter 2022, and here’s what they had to say. Don’t miss out on all the other knowledge and wisdom provided by the more than 40 biopharmaceutical executives taking part in this year’s annual outlook by becoming a Life Science Leader subscriber today.

What Manufacturing Trend Sparked By COVID-19 Do You Anticipate Continuing Into 2022 And Beyond?

William (Bill) Monteith, COO, StrideBio: The biggest trend regarding the global supply chain, sparked by COVID that I see continuing into 2022 is the shortage of key materials combined with long lead times for manufacturing. We have seen lead times for equipment, raw materials, and consumables go from a few weeks to a year or more. I see this as due to two issues: first, the pandemic’s impact on labor availability for the manufacture of these materials – especially any that utilize resins or chips in the making or packaging of these materials; and second, the DHHS’ [Department of Health and Human Services] designation of priority of these materials to those companies making products for the pandemic. This causes companies developing critical products for rare diseases or cancer treatments unrelated to COVID to rethink their supply chains, safety stocks, and procurement expenses. They end up vying with other companies for these materials. Increasing order quantities and safety stock ties up funds that could be better utilized in development, preclinical, and clinical activities. This places additional financial and development timeline constraints on start-up or early-stage companies to develop their products and get them to the clinic. As a result, non-COVID related treatments for serious diseases that may not have a current standard of care are delayed. I think the industry, working with regulatory and government agencies, needs to address this issue quickly to avoid new (non-COVID) health concerns in the general population.

What Manufacturing Trend Do You Anticipate Having The Biggest Impact On Biopharma Over The Next 10 Years?

Jason Burdette, SVP technical operations, Paratek Pharma: Supply chain redundancy will have the biggest impact on biopharma over the next 10 years – not just with respect to “why” companies build that redundancy, but where they build it.

Recent increases in supply chain redundancies are fueled by multiple factors impacting supply, manufacturing, and logistics and were accelerated by the COVID-19 pandemic. Practically overnight, single-source supply chains were interrupted, underscoring the need for redundancy.

The pandemic also changed the industry’s thinking about redundant locations. Companies utilize computational models to assess supply chain risks and their impact. They then select a redundant location based on computational predictions that the risk of a supply chain-disrupting event simultaneously striking both locations – for example, China and Eastern Europe – is low. Yet in 2020, that kind of low-risk event is exactly what happened: a global pandemic that affected everywhere at once.

Mitigating the risk of global supply chain disruptions means building redundancy close to home to remove as many transition points in the shipping logistics as possible. For a U.S. company like Paratek, it means bringing that redundancy on shore, where we only need to consider shipping across state lines, not across one or more international boundaries.

Leslie Wolfe, Ph.D., head of chemistry, manufacturing & controls, Generation Bio: Over the next 10 years, it is likely the use of cell reactor systems will decline, and more synthetic type production will be developed. Initial studies have shown the rapid enzymatic synthesis (RES) method is faster and gives higher yields and higher purity of drug substance. Taking advantage of these types of molecular processes involving restriction and DNA/RNA enzymes to amplify the quantity of the gene delivery nucleic acids will expand in the field. For example, Generation Bio recently announced a switch from cell-based production to RES to manufacture its DNA drug substance.

Additionally, during the past year and half, because of the pandemic, the supply chain for raw materials and components has become quite difficult to navigate. While the use of disposable and single-use systems will always have role in controlling cross contamination, this recent experience requires all manufacturers to consider the financial and infrastructure investment into reusable materials as part of their strategy. All sites will need to have some type of robust steam-in-place and clean-in-place equipment, such as glasswashers and autoclaves, not just as a backup but also as a primary source in case a supply chain problem occurs. Moreover, with the increased awareness around environmental impact and sustainability, advancements to perform these cleaning and sterilizations procedures more efficiently will be welcomed, such as the ability to reduce water usage to make steam or to shorten turnover times for equipment.

What Were Some Of The Best Practices Observed Around Cooperation Between Vaccine Manufacturers During The Pandemic, And Will There Be Greater Cooperation Between Biopharma Manufacturers In The Future?

Bryan Gillis, VP manufacturing, Rubius Therapeutics: Some of the best practices observed during the pandemic included collaboration between biotech and pharma companies, contract manufacturing organizations, tool manufacturers, and the government, which helped speed the manufacturing process and provided greater transparency throughout the process with an increased willingness to share intellectual property, which also expedited the manufacturing process.

Pharma manufacturing will largely go back to normal post-pandemic; however, the government and the pharmaceutical industry now have the tools and information needed to better prepare for future scenarios where such collaboration will be needed.

What’s The Next Big Thing In Biopharmaceutical Manufacturing?

Michael Paglia, chief operating officer of BaseCamp, Elevate Bio: A major trend in biopharmaceutical manufacturing will happen in the cell and gene therapy (CGT) space, where companies will begin process development (PD) in the earliest stages of product development. There are two reasons for this: the CGT space continues to grow exponentially, bringing products closer to commercialization, and, as “living drugs,” CGTs are not well-suited to the PD of other well characterized biologics.

Understanding the process parameters affecting critical quality attributes of a CGT product prior to Phase 1 is key to helping to avoid costly comparability between IND-related material and commercial material later in development. If a company cannot demonstrate comparability, it may not be able to use early-stage clinical data to seek regulatory approval and will have to repeat clinical trials using the commercial material.

Correlating process parameters with a product’s preclinical performance through robust assays early in development also enables fine-tuning of the product’s effectiveness before entering a clinical trial. For example, the potency of a cell therapy often depends on multiple cell types or subtypes, so correlating preclinical efficacy with the ratios of specific cell types and identifying the process parameters that determine those ratios are essential to successful manufacturing and early phase clinical trials.