Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Chris Spivey

, Bob Girton, Partner, Edgewater Capital, spoke to 

about how pharma manufacturers should approach building Environmental, Social, and Governance (ESG) within their business operations rather than having it run as a parallel program. Girton will be moderating a panel discussion "

Best Practices in Implementing a Successful ESG Framework

Can you give an overview of the current status and activities of ESG practices in the pharma industry?

: Pharmaceutical companies have long been active in ESG practices. As with the broader efforts around corporate responsibility, those efforts have accelerated in recent years, especially at large multinationals. Most large pharma organizations have set and communicated clear, specific targets, often targeting their greenhouse gas emissions through zero carbon emissions as well as reductions in both input and waste streams. New regulation in both the EU and the US will bring this individualized patchwork closer to a unified effort by setting more consistent requirements and alignment around transparency and reporting. 

Further, these requirements have in recent years been filtering down into small and medium organizations either directly, in order to meet the expectations of their respective stakeholders, or indirectly through the scope two and scope three requirements of the multinational enterprise (MNE). Notably, the direct impact represents the broadest population of companies, and often, these organisations are the most resource constrained and inexperienced in addressing these requirements. That said, to be competitive in the marketplace, this is no longer optional.

In addition to environmental and climate concerns, pharmaceutical companies are working to address social concerns, which focus on equitable access to healthcare. One way this is being put into action is the distribution and pricing of pharmaceuticals and increased diversity and transparency within clinical trials.

What are some common pitfalls? How should pharma manufacturers incorporate those needs?

: There's a lack of clarity on what we really mean by ESG, so breaking down the phrase into a series of actions would be one. Then with the large multinationals, another challenge is that they are applying expectations right down into their vendor network—which might be undeliverable in the way they envisage it, especially without the larger company’s support, guidance, and engagement. So, the main risk is that it can often become little more than a check box exercise. What you don’t want is ESG operating as an island separate unto itself, something that is not embedded in the business.

And this is where we get to the crux of the matter—how and why do you create the business case for ESG? You need to create something or an initiative that is also impactful on the business. To give you a specific example, a company of ours is using green chemistry. They are not undertaking this because its "green" but because the chemistry is better. It's a better solution. And so the business case is embedded inside of what you're actually innovating to the core.

My advice to manufacturers is to stop and review: ask if we go down a climate focused or carbon credit or a diversity, equity and inclusion (DEI) program at our firm, why are we doing it? How is this going to impact how we operate, what decisions we make, what priorities we set, how will it actually make the organization better? And not just going through the motions because a large multinational customer required it; that said, MNEs are requiring it.

The organizations Edgewater works with are typically 20 people to 300. This means for ESG, as in many aspects of our businesses, we are resource constrained, so whatever we identify as ESG initiatives, must also be impactful to the organization.

Does venture capital or private equity money going into CDMOs look for this infrastructure to be in place before investing?

Yes they do, and they want to know that at least the framework of ESG is starting. That's a positive for us. Our investors expect that of us, and I think it speaks of the maturity and awareness of the leadership. In the same way we’d also be looking at tracking their safety statistics. Ideally, we want them to be laying out the plan for the next five years and how they will actually put those checklists, into action.

As an example, at Edgewater we have a shared DEI program that sits across our organizations. Each business has selected a DEI advocate that sits on the council and shares ideas and accountability across our business. As there is no one size fits all, we have established a list of actions and best practices. Beyond helping identify what’s possible, it also helps to establish a shared language. From this "menu”, our DEI council has selected a small number of “must dos”. These are the critical few and serve as a point of anchor or foundation. Beyond the “must dos” the organization may select a series of “may dos”. Taken together, the “must dos” and “may dos” must be linked into what we’re building at each of our organizations. It has to be in our strategy plan, our budget, key performance indicators, and management by objectives for the year, along with clear actions we will take to achieve them.

What also helps with deciding when and what to implement is knowing your customers, knowing your market, being out there, asking the questions, and continuing to revisit the untested. And you may choose not to implement right away, but you're aware that at some point, when I need it, I'll know when to make a trigger point or when to make the decision. And it's going to be around the needs of your customers, as buying some of pilot pieces of equipment for say, continuous manufacturing / flowchemistry—they are not that expensive. Getting the capability and then starting to play with it or maybe partnering with an academic lab. There are a lot of ways to sort of test and feel without actually going the next step. So, I think it's more just a case of being aware of what's going on in your market, rather than saying, I'm just going to ignore it and not implement in methods that are more ESG compliant. The cost of access is so inexpensive now that it's more of a time resource and efficacy than it is dollar concern.

 What will ESG in pharma look like in five years?

: In one line—it will be so much a part of the whole system that we won’t be hosting panel discussions on how it’s supposed to be built and implemented. I strongly believe that if companies adopt measure to be more environmentally and socially responsible, in a way that also impacts its business and operations in a positive manner, others will follow. It will not only be the right thing to do but will also make a lot of sense. Climate change is real and needs immediate attention. Pharma industry, being a major carbon producer, has a huge responsibility to take swift actions that are effective and sustainable in the long run and ESG compliance is the step in the right direction. Additionally, your employees, especially younger generations, expect our organizations to be diverse, equitable, and inclusive. We know that diverse and inclusive teams are much more effective.”

Articles

Bob Girton, partner at Edgewater, discusses best practices for how pharma manufactures should incorporate sustainability into their operations.

CPHI North America: Investors and Pharma Expect Manufacturers to Build ESG Into Operations

World leaders have set ambitious goals to respond more swiftly to the next pandemic, including the United States’ goal to design, test, and review a new vaccine just 100 days after a pandemic declaration and to produce enough vaccines for the US and the world in 130 and 200 days. Past preparedness efforts have focused on innovation and reliability—culminating in the novel mRNA vaccines. Today, it’s important to consider diverse responses—and how the industry can make investments sustainable and “ready” for when an emergency happens.

The Real Message Behind Commercial mRNA Products


eBook: The Real Message Behind Commercial mRNA Products
April 2023
Pages: 6–11

When referring to this article, please cite it as Spivey, C. Learning to Think at Lightspeed. 

Pharmaceutical Technology's The Real Message Behind Commercial mRNA Products 

Actions combatting the next pandemic must be diverse, reliable, and sustainable.

Learning to Think at Lightspeed

Nicole Lewis, PVP Program Manager at Boston Children's Hospital, discusses the science behind precision vaccines, a form of personalized vaccines.

Unpacking Precision Vaccines with Nicole Lewis (World Vaccine Conference 2023)

Marcel Baumann, business development director at Recipharm, discusses soft mist inhaler technology from the show floor at the World Vaccine Conference.

Discussing Soft Mist Inhaler Technology with Marcel Baumann (World Vaccine Conference 2023)

A paradigm change, regulatory expansion, and some positive reimbursement outcomes have led to an inevitable trade imbalance between the supply and demand sides of the advanced therapy medicinal products (ATMP) field. “Demand for these often-curative therapies far outstrips supply, with a current inability to mass produce these personalized medicines” states Farlan Veraitch, founder and chief scientific officer at Ori Biotech Ltd.

“Alternative technologies in development—including donor-derived allogeneic approaches and 

 gene-modified cell therapies (1)—are promising in many therapeutic areas, but are likely many years away and come with their own set of challenges and, therefore, are unlikely to obviate the need for patient-derived therapies,” says Veraitch.

Limitations of current methodologies for cell therapy manufacturing have been well documented. Processes that have progressed farthest have been modular, semi-automated processes that still contain manual handling steps. “This style of process is inherently limiting,” says Peter Yates, director of Product Management–Personalized Medicine, Cell and Gene, Lonza. “These processes may work well in early clinical trials where the numbers of doses produced is relatively small and demand can be handled with a specialized manufacturing team,” continues Yates. “However, the problems become abundant when trying to increase throughput … our goal is to standardize and automate as many unit operations as possible to simplify handling and reduce operator interaction. A key aspect of this is to maintain flexibility in programming, to allow the unique manufacturing specifications to be retained. So as iterative changes need to be implemented, you have a platform that accommodate changes in a controlled way,” he emphasizes.

Looking at the challenges in learning to scale based on past success in certain biologics, Yates clearly states, “The underlying issue in scaling autologous cell therapy manufacturing has been how to do so economically. Groups feel a push to generate clinical data as quickly as possible to support additional funding rounds. This can lead to manufacturing processes based on immediate necessity versus long term scalability. Essentially kicking the can down the road on the issue.”

® have heard similar descriptions from multiple industry contacts. Nicole Faust, general manager Cell Line Development at Cytiva, has excellent perspective, encapsulating this point by describing “when we think about manufacturing, initially a lot of thought was put into the design of vector, how you have to make it an efficient therapeutic. Nobody thought too much about production methods. So basically, the first products went into the clinic, and even went to market, with the production methods as they had come out of university—using adherently growing H2K 293 cells doing a plasmid triple transfection. That works perfectly fine in an academic [setting], it also works well for a limited number of patients, but then when you really go to market, of course you need reproducible technology, you need scalable technology, and that challenge had to be tackled then for the adherently growing 293 cells and the triple transfection—elegantly solved by fixed-bed bioreactors, like the iCELLis by Pall for example, but the technology still faces limitations; the scale is limited and you still have to bring in plasmid DNA for each production batch; you have to bring in transfection agents for each production batch, reproducibility of the batch is a challenge; and when you go to the more prevalent disease, that’s when it gets really challenging. So, the first improvement that the field has taken is to move from adherently growing cells to suspension cells.”

Small-footprint automation to redesign CAR-T production

Initial efforts to automate autologous CAR-T production focused on repurposing technology that was designed for single-batch manufacturing of antibodies and other therapeutics, including those based on viruses and stem cell therapies. The equipment had large space requirements and required a skilled workforce in order to scale up.

Veraitch points to liquid handling as a major bottleneck requiring new ideas. “Approaches based on typical bioreactors require extensive networks of tubing, which introduces a high degree of complexity and risk into the process. The staff required to manage such systems is difficult to deskill, as it requires a large GMP-level team with both scientific T-cell expertise and training in the complex protocols involved with tube engineering … Tubing needs to be accessible, which means that the entire system needs to be at bench height to allow operators proper access. If scaling up means adding identical enclosed automated systems, expansion is then effectively restricted to scaling out (in only two dimensions), as stacking would be impractical. Tubing, then, roughly correlates to a massively inefficient use of space. These two factors explain why such approaches have so far failed to significantly bring down the cost of goods: they don’t reduce the demand for skilled labor, and they fail to reduce the amount of GMP space required to make a CAR-T dose, even when using first generation automation,”
he concludes.

Himanshu Gadgil, CEO, Enzene Biosciences Ltd, agrees, commenting that “new filtration technologies that are resistant to choking” is of the highest priority. He goes on to add that “PAT [process analytical technology] needs to come to allow real-time process control,” along with “integrated at-line analytical methods for real time CQA monitoring… [inclusive of] inline bio burden and endotoxin control and Bioreactor design for high density cell cultures.”

Reem Eldabagh senior Upstream Processing Scientist at Merck, concludes this thought saying, “With the advances in automated technology, autosamplers have brought about a much-needed decrease in time-consuming manual labor increasing workflow efficiency and sampling frequency and enabling conclusions based on data-rich analyses. These automated technologies, however, are not free from challenges, a prominent one being their integration and seamless communication with reactors and analyzers and their own pre-existing software.”

Automation and digitalization, a step toward continuous manufacturing?

Process intensification advances have recently been significant and, in some cases, surprisingly impressive (including higher yields per cell, and more full versus empty capsids), but replicating the same efficiencies of monoclonal antibodies, for example, remains an aspirational dream. Veraitch avers that, “Large-batch approaches that have worked for antibodies or small molecules will never be viable for autologous cell therapies, and even allogeneic approaches would operate at much smaller scales. As each patient-derived therapy dose will continue to require individual, sequential processing, the goal must be to intensify an automated workflow—shrinking the manufacturing footprint, increasing throughput, increasing quality, and dramatically lowering costs. To do so, the process steps should take place in an enclosed system that can multi-plex, without a high reliance on overly complex, tube-based liquid handling. As a result, the remaining manual steps would become deskilled, freeing PhD-level GMP manufacturing specialists for high-value tasks more suited to their training … But automation and flexibility are often at odds with each other. This delicate balance between automation and flexibility is a challenge that we continue to tackle and have support packages that cater to both.”

For his part, Yates is buoyed by recent successes, saying, “We are continuing to invest in onboard in-line analytics and see this heavily requested from the field. There is a need for robust analytical tools during process development that can provide real-time feedback. However, there still exists an integration and technological gap that allows these assays to be run inline and autonomously, especially with assays measuring functional capabilities and not just phenotype or viability. This need is further exacerbated as we inch closer to decentralized and point of care manufacturing as QC [quality control] will be central to its success. Moreover, automation and simplification of assays will be critical for their use in non-centralized
manufacturing systems.”

Digitization will be key for the more efficient logistical movement of products throughout production. The centralized manufacturing approaches that work for small molecule production have become extremely problematic for cell therapies.

Veraitch points to the future saying, “The cell therapy manufacturing space is approaching a critical juncture—with enough data to clearly understand why existing approaches are insufficient, but before they become too entrenched to dampen the field’s long-term potential. The goal remains to make the highest-quality therapies accessible to the most patients, which can only be done by reinventing both the physical and digital footprint of cell and gene therapy manufacturing.”

When referring to this article, please cite it as C. Spivey. Small Footprint Automated Closed Production Platforms for CAR-T and Other Advanced Therapies. 

Limitations in production platforms have impeded continuous manufacturing for advanced therapies. 

Small Footprint Automated Closed Production Platforms for CAR-T and Other Advanced Therapies

Does Pfizer’s outbidding of Merck in the acquisition of Seagen consolidate gains for patients given the up and down history of the antibody drug conjugate (ADC) field and funnel new oxygen into novel applications? Or does this merger winnow down alternatives and close commercial paths for otherwise promising but currently overlooked ADC entities?

The history of gemtuzumab ozogamicin—first approved in 2000, removed from most markets in 2010 (except Japan), then reapproved by FDA and the European Medicines Agency (EMA) in 2017 (based on that Japanese data)—underscores the bifurcated belief in the ADC approach itself. This drug was the product of a collaboration between Celltech and Wyeth that began in 1991. The former being acquired by UCB in 2004, the latter acquired by Pfizer in 2009 (1). The German Nobel laureate, Paul Ehrlich, came up with ADCs way back in 1900, famously describing it as Zauberkugel, a “magic bullet” due to its potential to target only cancerous cells, leaving healthy cells free to go about their normal lives.

“Four of the 12 total FDA-approved and marketed ADCs [are] using its [Seagen’s] technology … Seagen’s portfolio includes four approved medicines that are first- or best-in-class in their respective indications across solid tumors and hematologic malignancies, including three ADCs: ADCETRIS (brentuximab vedotin), PADCEV (enfortumab vedotin), and TIVDAK (tisotumab vedotin) ” (2, 3).

My own take is this acquisition is a magic bullet for filling Pfizer’s innovation duties in their oncology portfolio. They can “bolt on” much of their small-molecule knowhow as an added bonus, for other therapeutic indications, potentially expanding physicians toolboxes. Equally, it’s a win for patients generally, as Seagen said on a call “there’s opportunities, not just with immune checkpoint blockers, but to increase further the antibodies, but also the linkers, as well as the payloads ... to expand across many novel tumor types, not only hematologic.” So, more types of magic bullet for more patients over time.

1. Sorkin, A.; Wilson, D. Pfizer Agrees to Pay $68 Billion for Rival Drug Maker Wyeth. 

2. Pfizer. Pfizer Analyst and Investor Call to discuss Proposed Acquisition of Seagen, March 13, 2023.

3. Pfizer. Pfizer Invests $43 Billion to Battle Cancer. Press Release. March 13, 2023.

When referring to this article, please cite it as C. Spivey. The Commercial Message mRNA Products Send. 

What can we take away from Pfifzer's acquisition of Seagen?