Mike Hennessy Jr. is the President and CEO of 

Mike Hennessy Jr.

As we reach the midpoint of the year, it’s appropriate to reexamine the topics we’re addressing. I’d like to point to a special podcast Pharmaceutical Technology conducted where Editorial Director Chis Spivey talked with the director of FDA’s Office of Pharmaceutical Quality (OPQ ), Dr. Michael Kopcha, and his deputy directors Dr. Sau Lee and Dr. Cindy Buhse about advancing the science of pharmaceutical manufacturing. Discussion encompassed the framework for regulatory advanced manufacturing evaluation (FRAME), quality management maturity ratings (QMM), advanced versus traditional manufacturing, and re-shoring drug manufacturing to the United States. But I particularly want to highlight the emerging technology program (1).

These new technologies initially were brought to FDA by industry and are, therefore, a fascinating window into where the industry believes it is heading. In this respect, Mike Kopcha said on the PharmTech podcast that, “... to address current and potential future innovations ... we worked with NASEM (National Academies of Science, Engineering and Medicine), they held a public workshop, brought in industry experts in this area, to be able to talk with us about what was going on in the industry, what’s on the horizon over the next five to 10 years. ... I can list some of the more significant ones ... end to end manufacturing, distributed manufacturing, point-of-care manufacturing (as the name implies, doing manufacturing right at the point of care where the patient or consumer actually is), and artificial intelligence, in order to understand what the regulatory framework should look like, we needed to know what these technologies were ... so we knew what we were going to be asked to evaluate, and eventually regulate.”

Our new series, “Weighing Up Big Pharma” directly addresses large company performance vis-à-vis their ability to leverage artificial intelligence (AI). With batch values occasionally rising to $3 million dollars, and data streams proliferating both in terms of total amounts but also depth of insight, it is totally logical that pharmaceutical manufacturing has increased the use of AI. Multivariate mechanistic modeling and digital twin strategizing are two areas that leap to mind. But predictive maintenance and advance failure warning systems play an increased role in reducing costs. One example is water purity control. Having to fix a plant’s water system after a problem not only costs in terms of wasted product, but also in terms of lost operating time, until all systems are back online (2). Is AI a panacea for pharma’s productivity gap? As a disruptive force which, “...promises to help speed up drug identification; improve patient selection; creating digital twins; improve manufacturing; tailor marketing material; enhance customer engagement; predict chronic diseases; and support health equity” (3), you can see why the director of FDA OPQ wants to understand more about AI, and why we will all benefit from a better understanding of this increasingly powerful tool.

1. C. Spivey, “FDA Weighs in on Advancing the Science of Pharmaceutical Manufacturing,” Drug Solutions Podcast, 

2. D. Greenfield, “How and Why Pharmaceutical Manufacturers Are Applying Artificial Intelligence,” 

3. C. B. Hartley, “Weighing up Big Pharma,” 

When referring to this article, please cite it as M. Hennessy, “Is AI a Panacea for Pharma’s Productivity Gap?,” 

Articles

AI could provide solutions to critical manufacturing inefficiencies.

Is AI a Panacea for Pharma’s Productivity Gap?

Spring is a time for renewal of energies, setting fresh goals and making new friends. As we have done for many years, Pharmaceutical Technology is proud to organize the keynote sessions at the upcoming INTERPHEX exhibition in New York, which is being held May 24–26th. These presentations are a snapshot of where the focus of energies and resources have been placed in the year leading up to the event, and for the following year or two, thereafter. Session and panel discussion this time include topics of continuous and modular manufacturing advances, emerging therapy constriction points, fresh challenges emanating from emerging therapies, and an overall big picture last afternoon session and panel discussion. Each incarnation is an opportunity to highlight industry trends, obstacles, and cooperative programs. Represented this year are diverse companies, universities, and organizations such as the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), Rutgers University, CONTINUUS Pharmaceuticals, Inc., Entegris, Tessera Therapeutics, MilliporeSigma, the New York Genome Center, the University of Pennsylvania, and a brand-new entity, named AexeRNA. 

There are one or two familiar faces but generally these are new voices and perspectives giving intriguingly titled talks such as “New therapeutic Modalities and Moores Law in Biomanufacturing”, “Programming the Immune System to Supercharge Cancer Cell Therapies”, and “Considerations for a Unified Pandemic National Response”. It is this kind of gathering that forces one to confront how our industry traverses a broad sweep of technologies, skill sets, and therapeutic applications. The frenetic pace of the past couple of pandemic years has paradoxically invested fresh impetus and outreach, instead of wearing us down and leaving us effete. Lessons learned in the face of adversity can now be applied to mitigating some of the harm from whatever future emergencies we will face. I expect some of the solutions we will rely on going forward will be presented at the INTERPHEX keynote sessions. Only by listening to others, and by joining forces, can we optimize our individual talents. In spring, we renew our pledge to make a difference, and grow together as an industry.

When referring to this article, please cite it as M. Hennessy, “Back to INTERPHEX,” 

Spring has returned, and with it comes INTERPHEX.

Back to INTERPHEX

If a major league team was guaranteed to lose half of its best players (by far) over the next few seasons, the outlook would be gloomy. Our industry will lose core patents on Humira,

Keytruda, Revlimid, and Eliquis shortly, with another slew of top sellers not long thereafter. Boardroom speculation has been rife with patent thickets and discussion regarding the technical challenges in producing generics for large complex biomolecules. But the obvious is true, this will happen, it will hurt, and some will feel the pain far more than others.

One might suppose the boardrooms of AbbVie, Bristol Myers Squibb, Merck, and Pfizer must feel most under siege. But while the threat falls heaviest here, these companies have also fortified and reconfigured their operations the most, and have had the most money to do so. Mergers and acquisitions, while comparatively quiet the past year or so, are boiling away beneath the surface. More useful to the long-term interests of the pharmaceutical industry, however, are investments in new approaches, novel technologies, and fresh ways of thinking.

When the overall economy looks set to accelerate, that effect is first felt by architects. They first receive the funds to draw up blueprints for what building(s) comes next. In the pharmaceutical industry, that bellwether is the academic pharmaceutical scientist. If you speak with someone from this group recently, they are likely to tell you of conversations ongoing about pilot programs or proof-of-concept partnerships they are excited about. A few days ago when chatting with a professor of pharmaceutical sciences and chemical engineering, he surprised me by outlining a simple path to delivering drugs safely past the blood brain barrier. This membrane has been an obstacle to neuroscience pharmaceuticals for such a long time because it does its job so well—keeping out the larger molecules evolution has taught us to be conservative toward. Another scientist shared background about mapping counterfeit drugs and linking that geospatially to a rise in resistant infections in several geographies.

One need only draw up a compilation map of which disease areas, which technology advances, and which engineering processes are being redesigned in these academic conversations, to view a composite image of the biopharma industry’s next decade or two. A money-ball meets blink and the tipping point pharmaome, if you will. Reportedly, from these conversations, after many decades of setbacks, pharmaceutical neuroscience looks like having a better season ahead than, say, the New York Jets.

When referring to this article, please cite it as M. Hennessy, “Major League Moves,” 

Advances in pharmaceutical neuroscience present an opportunity for pharmaceutical companies to stay ahead of the curve.

Major League Moves

In April 2020, a clarion call by Outsourced Pharma set a major goal in “A Declaration of Drug Independence.” This call sought to “... dedicate ourselves to the goal of reducing US dependency on foreign sources for drug materials, intermediates, substances, and finished products to 50% or less by the end of the year 2025” (1).

In hindsight, this looks prescient, especially as war in Europe now joins the pandemic to threaten access to essential medicines. What looks less than prescient was the frequently quoted response in May 2020 from the Pharmaceutical Research Manufacturers of America (PhRMA) whose core reply amounted to, “But now is not the time for sweeping changes to the pharmaceutical supply chain that could cause disruptions” (2). Even taken in context, it’s a paradoxical statement.

Eric Edwards, CEO of Phlow, is focused to rebuild the critical industrial base that’s been lost over decades, “to be able to manufacture these essential medicines end to end, from chemistry all the way to the finished dosage form so that we can get it to the patients at the bedside.” Phlow emphasizes continuous manufacturing processes to “allow chemical reactions to run on a much smaller scale, over and over again, until an entire volume of an active pharmaceutical ingredient is produced, [which] has significantly lower labor requirements [as it’s highly automated]. Then you have to get it into that finished dosage form, and we’re starting by focusing on sterile injectable drugs. The reason we’re focusing on sterile injectable drugs initially is because the majority of drug shortages in America are sterile injectables” (3).

There are still reasons to hold on to optimism. Various aspects of continuous flow manufacturing, now adopted at higher rates, allow for increased production while maintaining reasonable cost conditions. There have also been investments made on national strategies, from BARDA and BioMADE and with genuine leadership shown from the National Institutes of Health, National Institute of Standards and Technology, and FDA. But using all our logic while avoiding half measures will be required to get close to the outlined goal. One of the upsides of being a conservative industry should, theoretically, have been holding on to control more firmly.

Our exciting new podcast series Drug Solutions explores this topic in depth this March through a lively discussion with Dr. Fernando J. Muzzio, Distin- guished Professor, Chemical and Biochemical Engineering, Rutgers Univer- sity and Frederic Kahn, VP Sales, Wavelength Pharmaceticals. Both are well respected from many years of excellent and devoted service to our industry.

1. Louis Garguilo, “Sign the '50 by 25' Declaration of Drug Independence,” 

2. Nicole Longo, “Executive Order Threatens R&D When We Need it Most to Fight COVID-19,” Blog Post, PhRMA, 

3. T.Giddens, “The Phlow of Things,” 

When referring to this article, please cite it as M. Hennessy, “Locating Logic in Pharma Manufacturing,” Pharmaceutical Technology, 46 (3) 2022.

Reducing US dependency on overseas pharma manufacturing may prove critical in navigating supply chain disruptions.

Locating Logic in Pharma Manufacturing

The JP Morgan Healthcare conference in San Francisco is the pharmaceutical world’s equivalent of the world economic development forum in Davos—an event CEOs and innovators schedule the rest of the year’s calendar around. It was with a heavy heart late last year the decision was made due to go to an all-virtual event. As a city, San Francisco was denied a vigorous financial stream, while participants were held back from in-person catchups and in-person partnering and deal making.

But much was maintained. The pandemic has raised drug production and supply to the forefront of both the general public and investors of various stripes—angel, institutional, strategic industrial, private investment in public equity, and public private partnerships.

This capital influx allows biotech companies the luxury of retaining control much longer (i.e., of staying private companies). In turn, this has pushed up sector valuations. So, while mergers and acquisitions remained somewhat quiet after a stellar 2019, licensing and partnerships predicated upon back-end payouts have proliferated.

This is in tune with a cultural shift during the two years of pandemic where all parties have kept in far closer conversation than had been previously typical. This built-up of trust and empathy for each other’s situations and goals, reduced barriers and resistance to license agreements. It’s been more collegial. Decisions are made with less uncertainty. Outsourcing contract development and manufacturing organizations (CDMOs) have space booked a year in advance, “the outside economic environment is encouraging,” Ramesh Subramanian, Chief Commercial Officer, Aragen, says. He affirms it is a buoyant time for R&D outsourcing. He specifies that this buoyancy can be attributed primarily to three reasons, “... increased funds flowing into [the R&D outsourcing] space, a high number of targets in the pipeline, and renewed interest in pharma R&D due to the COVID-19 pandemic.”

However you are placed coming out of the past two years, it is a certainty you are busy. And busy is good for business.


Volume 46, Number 2
February 2022
Page: 8

When referring to this article, please cite it as M. Hennessy Jr., “A License to Innovate,” 

A License to Innovate

Following a somewhat static decade, FDA has shaken up one half of the drug world by introducing the Novel Excipient Review Pilot Program. Proposals are accepted through Dec. 7, 2021. Universally welcomed, the pilot also carries a burden of very high expectations for being enlarged. Below are three veteran industry voices that harmonize in the hopes for more streamlined approvals.

As drugs become more complex and difficult to manufacture, the role of excipients becomes more pivotal. Dr. Stephen Hoag of the University of Maryland pointed out, in an interview with Pharmaceutical Technology, “It’s a real need of the industry ... the example right in front of us is the Pfizer and Moderna vaccine where the lipid nanoparticle for the delivery of the vaccines are very specialized excipients. They’ve created a platform that can be used for a lot of different possible disease states ... it’s a real need with these poorly soluble drugs, it would be nice to have a lot broader tool chest than what we currently have. And that’s why IPEC is really working on trying to streamline the pathway for approving excipients, obviously you need to worry about toxicity and protecting patient safety, but having said that, you need a pathway to get excipients approved, and IPEC is working to get that pathway as smooth as it can be.”

Chris Moreton of FinnBrit Consulting also considers the pilot positive, and said in an interview with Pharmaceutical Technology, “...applications must be in in early December. The sponsors of the excipients selected by the FDA will then need to submit their data package (CMC and safety/tox). If they do not have a complete package at the time of selection, they will need to provide a realistic timeline as to when they expect to have the rest of the data available. There are potential benefits for both excipient manufacturers and users. My personal hope is that the pilot will be successful and extended to cover the whole range of novel excipients.”

Combining these threads together Dave Schoneker of Black Diamond Regulatory Consulting stated in an interview with Pharmaceutical Technology, “[the pilot]...is a great step forward to improve innovation in excipient and drug development. However, it will be very important to open up the scope of the program after the pilot program, if it is successful, to all the various types of novel excipients such as co-processed excipients, higher levels of use and new routes of administration of existing excipients, and the use of existing food and cosmetic ingredients for first use in drugs. This will be critical to the overall success of the program since there will always be a limited number of NCE type novel excipients which require full toxicology programs costing millions of dollars. These other types of novel excipients will be what ultimately will provide the biggest overall benefits to patient-centric drug development, dosage form innovation, and improvements in advanced manufacturing methods.”

We will watch the pilot program progress, along with our colleagues, with both excitement and great expectations.