Mike Hennessy Jr. is the President and CEO of 

Mike Hennessy Jr.

High Angle Shot of a Working Desk of an Successful Person in Office with Cityscape Window View. | Image credit: © Gorodenkoff - stock.adobe.com

Despite the bio/pharma industry’s stringent regulations and general tendency to adopt newer technologies more slowly than other industries, automated processes and robotics are increasingly commonplace in manufacturing facilities. Although initially used to improve efficiencies of repetitive tasks, automation and robotics have become more sophisticated and are now being employed for a much wider variety of tasks, such as quality control, optimizing processes, and analyzing vast quantities of data (1).

A particular benefit of automating processes and/or using robotics is the reduction of human intervention and, thereby, human error or contamination. This benefit is particularly important for aseptic processing, where particulate generation must be kept to a minimum to ensure the safety and sterility of the pharmaceutical product being manufactured.

The utility of automation to improve efficiencies in aseptic processing is examined in greater detail in this issue’s cover story, which is featured on pages 10–13 (2). “Automating processes and bringing robotics into aseptic processing, together with single-use systems, [are] helping to streamline processes, minimizing human intervention and reducing the risk of errors or contamination,” explains Aimee Hodge from PCI Pharma Services in the article (2).

In the cell and gene space, a deal between Astellas Pharma and YASKAWA Electric Corp. has been formed that will focus on the digitization of cell manufacturing through robotics (3). Under the terms of the agreement, the two companies will seek to develop a platform that will use a humanoid robot, Maholo, to link early-stage research to commercialization of cell therapies (3).

Additionally, once created, the companies would consider allowing startups and academia to use the platform, which could lead to the development of an advanced therapy ecosystem that nurtures innovation. Startups and academia are not always able to commercialize their cell therapy discoveries as a result of the significant cost and manufacturing challenges that are inherent with these complex drugs (3).

1. Praxie. Transforming the Industry: The Advantages of Automation in Pharmaceutical Manufacturing. 

2. Thomas, F. Streamlining Aseptic Processes through Automation. 

3. Astellas Pharma. Astellas Announces a Collaboration with YASKAWA to Create an Innovative Cell Therapy Ecosystem through the Integration of Pharmaceutical and Robotics Technologies. Press Release, May 21, 2024.

Mike Hennessy Jr is president and CEO of MJH Life Sciences®

When referring to this article, please cite it as Hennessy, M. Automating Processes. 

Articles

Improved efficiencies and reduced costs are clear advantages of automating drug manufacturing processes.


Publisher's Note: Automating Processes

High Angle Shot of a Working Desk of a Successful Person in Office with Cityscape Window View. | Image credit: © Gorodenkoff - stock.adobe.com

Research efforts are continuing to expand in the area of biological therapies. These large-molecule drugs are proving to be significant revenue drivers for bio/pharma companies and are providing therapeutic options for disease areas that have previously suffered from unmet medical needs (1).

Additionally, biologics are useful in providing more targeted disease treatment when compared with small-molecule drugs and lessening the risk of side effects for patients. The targeted nature of these large-molecule therapies is explored in this issue’s cover story, featured on pages 10–13, along with the potential that technological advances hold in pushing future boundaries and some of the challenges facing both the development and manufacture of biologic drugs (2).

Advanced therapy medicinal products (ATMPs), which are promising and often curative biologic therapies, face their own specific development and manufacturing challenges. Scalability of manufacturing for these emerging therapies is a particular bottleneck and something that San Francisco-based Cellares, a self-titled integrated development and manufacturing organization (IDMO), has sought to change. In an interview with Pharmaceutical Technology® Group, Fabian Gerlinghaus, CEO and co-founder of Cellares, detailed how the company’s Cell Shuttle platform and integrated consumable cartridge automated platform can improve scalability of ATMP manufacturing (3).

The IDMO has also garnered interest from Bristol Myers Squibb (BMS), which joined the Technology Adoption Partnership (TAP) program in August 2023 (4). Participation in the TAP program has meant that BMS can use Cellares’ automated manufacturing platform for the manufacture of its pipeline products.

Most recently, in April 2024, BMS and Cellares built upon their relationship by entering into a deal worth $380 million, where Cellares will transfer select chimeric antigen receptor T-cell therapies onto its manufacturing platform, with the aim of meeting growing demand and improving turnaround time (5).

1. Bender, M. Pharmaceutical & Life Sciences Trends 2024. 

 (accessed April 24, 2024).
2. Thomas, F. Biologics On Target for the Future. 

, 48 (5), 10–13.
3. Spivey, C. Cellares Innovates with Automated Cell and Gene Therapy Platform. 

, March 7, 2024.
4. Cellares. Cellares Announces Bristol Myers Squibb has Joined Technology Adoption Partnership Program to Evaluate Automated Manufacturing of CAR-T Cell Therapy on the Cell Shuttle Platform. Press Release, Aug. 28, 2024.
5. Cellares. Bristol Myers Squibb and Cellares Announce a $350M Worldwide Capacity Reservation and Supply Agreement for the Manufacture of CAR T Cell Therapies to Bring the Promise of Cell Therapy to More Patients, Faster. Press Release, April 22, 2024.

When referring to this article, please cite it as Hennessy, M. Tapping into the Potential of Biologics. 

Technological advances are helping advance biologics development and manufacturing and reduce bottlenecks.

Tapping into the Potential of Biologics

Experts believe it is likely cancer cells are more common in the body than previously thought, but typically caught early and removed in the body’s cancer-immune cycle. When the system is in good working order (and protecting us), dead cancer cells release neoantigens, which are acquired by dendritic cells and moved to a nearby draining lymph node for disposal. Dendritic cells then present this antigen to T cells, which become effector T cells, and after a few more steps, “move through the blood toward the tumor tissue. These T cells then infiltrate into the tumor and recognize and bind the MHC-I–antigen complex presented by cancer cells through the T cell receptor. Through these processes, cancer cells are finally killed. …When cancer cells die and additional neoantigens are released, the immune reaction continues the cycle again from the first step. [However], in cancer patients, at least one of these steps is defective and the cancer-immune cycle does not work properly” (1).

The obvious utility in identifying tumor neoantigens is consolidating in weight and importance, leading to coordinated leapfrog advances in pharmaceutical sciences. But each patient has their own personal biology, creating their own personal tumor microenvironment (e.g., there are more than 24,000 distinct human leukocyte antigens) (2). A paper describing a powerful new identification platform was briefly discussed in an interview with 

® (3), where study author, Stephen Schoenberger, told 

 editor “we let the patient’s immune system tell us which mutations can be confirmed as neoantigens and then have asked whether there are bioinformatically quantifiable features of these mutations apparent in genomic sequence data. Our goal in doing so is a computational prioritization algorithm of sufficient predictive power as to obviate the need for 

 functional validation step, as this would be difficult to scale for the number of patients that our findings suggest could benefit from personalized immunotherapy” (3).

Kim, S.; Cho, S. The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment. 

. 2022 May 24:13:868695. DOI: 10.3389/fphar.2022.868695. eCollection 2022.

Fu, L.; Huang, C.; Huang. Z. Neoantigens: Promising Targets for Cancer Therapy. 

. 2023 8 article 9. Nature.com, https://www.nature.com/articles/s41392-022-01270-x

Spivey, C. Research into Cold Cancers Heating Up. 

When referring to this article, please cite it as Hennessy, M. May I Present the Neoantigen. 

Experts believe it is likely cancer cells are more common in the body than previously thought, but typically caught early and removed in the body’s cancer-immune cycle. When the system is in good working order (and protecting us), dead cancer cells release neoantigens. 

May I Present the Neoantigen

Novo Holdings’ acquisition of Catalent, in retrospect, was entirely logical (1). We are tempted to see echoes of Thermo Fisher’s buyout of Patheon, or Lonza’s swallowing of capsule maker Capsugel. But this situation is different. Catalent makes significant production of Novo’s Ozempic and Wegovy, but also Lilly’s Mounjaro and Zepbound. And while Catalent’s acquisition is definitely about making drugs, it’s also very much about making money.

Making money takes various forms—taking away a competitor’s capacity to do so is doubtless one of the more intriguing variants. David Ricks, Lilly’s chief executive, was quoted as saying, “the reality is there just isn’t built capacity that’s available. These are technically complex facilities, there’s not an infinite number of people who know how to set them up. And the supply chain for the machines that make the products is also constrained” (2).

An interesting ironic side note is that Catalent has had a checkered compliance past. FDA visited the company’s Brussels plant in October 2021 and August 2022. Reuters reported that “inspectors said the lapses at the plant … represented the most serious form of violations, according to the reports, which show Catalent shut the facility down twice between the two inspections” (3). Reuters goes on to say, “at a meeting with Novo executives in May, two investors out of a group of about five expressed concerns about the choice of Catalent as manufacturing partner, citing the contractor’s history of compliance issues with FDA, according to one of the shareholders who was present. The investor, who declined to be named due to the sensitivity of the matter, said Novo’s Chief Financial Officer Karsten Munk Knudsen had responded by saying that, in hindsight, the company may have made a mistake in choosing Catalent and was now tightly overseeing the firm’s filling operations of Wegovy in Brussels” (3).

Novo Nordisk and Eli Lilly are spending heavily to boost their manufacturing capacity. “That could help them fend off competition from specialized pharmacies that are making generic versions of semaglutide and tirzepatide, an option created by the FDA designating the drugs in shortage” (2). Nevertheless, Anat Ashkenazi, Lilly’s chief financial officer, said in the Post article, “we intend on holding Catalent accountable to their contract with us” (2). Given new ownership, its uncertain if Lilly will be first in line, on the production line.

Catalent. Novo Holdings to Acquire Catalent. Press Release. Feb. 5, 2024.

Gilbert, D. Makers of Ozempic, Mounjaro Race to Meet Demand for Weight-loss Drugs. 

Fick, M. Insight: Wegovy Weight-loss Injection Factory Plagued by Sterile-safety Failures.

When referring to this article, please cite it as Hennessy, M. First in Line on Catalent’s Line. 

While Catalent’s acquisition is definitely about making drugs, it’s also very much about making money.

First in Line on Catalent’s Line

Given its positioning at each new year’s commencement, the J.P. Morgan Healthcare conference helps establish the tone with which the pharmaceutical industry is viewed. It is rare for major new announcements to be made at the conference; rather, its prominence is due to its capacity to sum up and condense the lessons learned from the past year’s fray.

As such, both Lisa Gill, senior analyst covering Health Care Services, and Chris Schott, senior analyst at J.P. Morgan covering US Diversified Biopharma, emphasize the salience of the current generation of weight loss drugs. Schott stated that, from an investment perspective, due to pharmaceuticals underperforming in 2023, “investor sentiment is pretty bearish for 2024 … as [the sector] is a well-positioned group, at record low valuations” (1). Schott goes on to say, “the GLP-1 weight loss drugs are projected to hit $100 billion in prescription sales by early 2030s, making it the largest therapeutic market we’ve ever seen, … and to alleviated bottlenecks, production capacity is expected to double in 2024, and rise again by 50% in 2025” (1).

While recaps are certainly useful, it is salutary to point out 

 was investigating GLP-1 performance in 2022, and asking, are obesity drugs the next blockbusters? 

 pointed out, “Novo had to revamp its production due to high demand for Semaglutide and some setbacks with manufacturing facilities. Overall, reliable API suppliers and contract manufacturing organizations (CMOs) are key factors in market success. Indeed, to solve such potential manufacturing obstacles, many companies opt to build in-house capabilities instead of relying on CMOs. Novo decided to build three new manufacturing facilities. This step will increase manufacture of its APIs, while also being able to assemble and package the oral and injectable products.” Necdina further emphasized potential production bottlenecks saying, “Eli Lily, a new potential player in obesity market, seems to understand manufacturing challenges. They plan to expand manufacturing footprint in Indiana by investing $2.1 billion in two new manufacturing sites” (2).

Gill, L; and Schott, C. 42nd Annual J.P. Morgan Healthcare Conference, J.P. Morgan Health Events website, 

https://www.jpmorgan.com/about-us/events-conferences/health-care-conference

Necdina, M. Are Obesity Drugs the Next Blockbusters? 

When referring to this article, please cite it as Hennessy, M. J.P. Morgan Losing Weight. 

Given its positioning at each new year’s commencement, the J.P. Morgan Healthcare conference helps establish the tone with which the pharmaceutical industry is viewed.

J.P. Morgan Losing Weight

In June 2023, FDA Commissioner Robert Califf ascribed most drug shortages to “generic-drug companies going out of business, either because they fail to invest in quality operations or because they can’t make a profit, as hospitals and pharmacies seek lower prices” (1). Chris Spivey, editorial director of 

®, wrote about Beyfortus being in shortage partly because of unanticipated high demand, but also pediatric practices. Unsure of reimbursement timelines and amounts, it experienced a vaccine hesitancy of the financial kind. Pediatric practices didn’t want to hold on to lots of $500 a shot doses (2).

On Dec. 5, 2023, the US Senate Finance Committee held a hearing on drug shortages. Marta Wosinska, senior fellow at the Brookings Institution, testified that generic sterile injectable (GSI) drugs represent about half to two-thirds of all shortages. GSI shortages result from how hospitals buy GSI drugs, and the underinvestment in manufacturing operations that follow. Wosinska stated GSI shortages result primarily from “manufacturing quality problems at facilities where the final product is made, often in the United States … What is vexing about those shortages,” she continued, “is that they are largely avoidable. All payers, including Centers for Medicare and Medicaid Services (CMS), reimburse hospitals in ways that give them incentives to use the lowest-priced GSI drug available … The price pressures put on manufacturers create a dynamic where there is little room for—or little return on—investing in manufacturing facilities, staffing, and oversight. [GSI drugs are hard hit] because making those drugs requires specialized facilities where employees follow complex manufacturing processes and controls. If we want to address the persistent GSI drug shortages, CMS will need to pay hospitals differently, incentivizing them to consider reliability of supply in their purchasing decisions … CMS does not have the authority to set up such a program, especially one that is not budget neural. This Committee however can grant that authority” (3).

Wechsler, J. Drug Shortages Continue to Plague FDA and Manufacturers. 

Spivey, C. Why We Were Not Properly Winterized for RSV Season. 

Wosinska, M. Testimony before the Senate Finance Committee, December 2023.

When referring to this article, please cite it as Hennessy, M. Reimbursement Precipitating Shortages. 

GSI shortages result from how hospitals buy GSI drugs, and the underinvestment in manufacturing operations that follow.