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

Chris Spivey

Pandemic shortage of test animals increased focus on alternatives, with renewed attention on approaches that had reliable supply infrastructure, could find failures sooner, and markedly reduced timelines and overall costs, while revealing fresh aspects of biology. So, what’s the holdup to widescale industrial adoption to 3D cell cultures? Other than being simply unproven, initial costs are much higher; learning or creating processes take more time, skill, and expertise; there exist no commonly agreed upon standards; and there is a lack of reproducibility. Additionally, for some applications, there were technical stumbling blocks. Efforts directed toward actual organoid replacements for heart, liver, or kidney necessarily required artificial vascularization to support tissue functions for processes such as cell feeding, oxygenation, and waste elimination. Without vascularization, those kinds of biological operations could only be performed through the very poor relative to vascularization, diffusion.

However, for other applications, a lack of vascularization actually more closely mimics the 

 state of many cancer cells and tumor microenvironments. Furthermore, studies have also shown a difference in gene, protein, and cell receptor expression. These differences deliver more realistic responses to such key cell interrogations, and better elucidate roles and requirements for proliferation, angiogenesis, and chemosensitivity (1). Most impressively, only 3D cell cultures reflect the hierarchical structure and cellular heterogeneity that mirror in vivo cell morphology, cell-cell interactions, and diffusion barrier activities (2). The kinds of information most sought after, anyway.

What I would like to draw attention to is a small Israeli company called Tissue Dynamics LTS, who estimates (in a dramatic claim) that the company could cut drug development costs by 40–80%, and time required by 30–50% overall (3). Their approach is to ab initio embed sensors into the organoid while its being grown, which allows AI-driven computation to directly interrogate biology every step along the development process. “This allows the robot to start screening drugs against different models of disease. It can perform, by itself, safety assessments in the microtissues and identify the drug that works best and causes the least damage to human organs, and it does this extremely fast. We can do it in 19,000 tissue samples at once. It is the equivalent of [testing on] 5000 patients,” said Yaakov Nahmias, founder and chief scientific officer of Tissue Dynamics LTS (3).

2. A.W. Daus, P.G. Layer, C. Thielemann, S

3. Debbie Mohnblatt/The Media Line, “Israeli Biotech Company Says It Can Revolutionize Drug Development,” 

Chris Spivey is the Editorial Director for 

When referring to this article, please cite it as C. Spivey, “The Kinds of Information Most Sought After,” 

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3D cell cultures could provide key avenues to unlocking critical information.

Next Level Interrogation

 under the unassuming title “Filling the Gaps”, researchers from the Telomere-to-Telomere (T2T) Consortium have reported an advance that may prove instrumental in scientific understanding of human evolution. While the first full human DNA assembly is not yet completed, researchers disentangled most of the remaining 8% of the human genome by making sense of complex repeat sections of the telomeres and centromeres, including the “short arms” of the five chromosomes where centromeres are skewed toward one end.

Historically, these short arms have frustrated biologists – they were believed to operate genes encoding ribosomes, the protein plants of our cells, but a comprehensive understanding eluded them. According to Adam Phillippy, a bioinformatician at the National Human Genome Research Institute, T2T researchers now believe that short arms are likely hotspots for gene evolution. Because gene copies are “parked” there, they can mutate and take on new functions.

This catalog of duplications could be used to gain information on neurological and developmental disorders that are linked to variations in the number of copies of specific sequences. Additionally, Phillippy states that chemical modifications to DNA in the complex repetitive areas are likely to play a role in disease.

This role in disease centers around immunology and drug absorption could have wide ranging implications for drug targeting, delivery, and pharmacokinetics. Here we have the kind of dogged persistence, quietly executed in comparative isolation, that often is looked back upon as ground-breaking. Making sense out of what appears to most as random repetition is a common scientific undertaking. Finding out what lies beneath is of huge biomedical value and well worth pausing for a moment to celebrate.

Researchers from the Telomere-to-Telomere Consortium have discovered new properties about junk DNA that could have wide-reaching implications.

Research Shows that Junk DNA Encodes Essential Immune and Metabolism Instructions

As someone who helped invent and patent several types of biomedical instrument, I feel a traitor for writing the following: our market has unmet need for fast, accurate analytic tools. While I can certainly see why some will resist or equivocate in response, this is absolutely an opportunity and not censure.

It’s not just that messenger RNA (mRNA) needs to be rid of genetic impurities like truncated transcripts or incorrect DNA template, or that wrapping it in lipid nanoparticle formulation for delivery creates more complex analytic challenges. Other recently created, small-molecule less celebrated drug formulations also had a need for new or more powerful analytic tools. Plazomicin (marketed as Zemdri), a novel aminoglycoside effective against gram negative bacteria, required novel modes for development and manufacturing, but it also benefited from a specialized analytic tool, the QMS plazomicin immunoassay (1), for measuring quantities in human plasma while treating complicated urinary tract infections, for which it was FDA approved.

As written elsewhere, there is now also an overarching business imperative to deliver products by continually breaking previous speed record barriers. Once the rewards for increasing patent lifetimes by being earlier to market became tangible, this has provided sustained business impetus to accelerate every aspect that could potentially slow deployment and delivery, hence parallel and redundant capacities and the investment in buildings, manufacturing equipment, and now analytic tools.

When married to increased drug novelty and rising complexity, requirement to have actionable data this hour, not this week, month, or quarter, further deepens this unmet need. In pharmaceutical analytics, this might well be just what the doctor ordered. Don’t get me wrong, I am delighted capillary electrophoresis has made a reappearance, and we’ve imported various stripes of particle size analysis from material sciences. But I keep a weather eye for novel approaches, most especially those incorporating audacious physical determinations. When readers send descriptions about good methods they’ve personally used, we’ll find a way to incorporate them in our coverage. That really should add intensity and drama to analytics, and a dash of new character!

1. C. H. Lias, Letter to Microgenics Corporation, 

When referring to this article, please cite it as C. Spivey, “Characterizing the Unseen Drama of Analytics,” Pharmaceutical Technology, 46 (3) 2022.

Chris Spivey is the editorial director of 

Borrowing is good, but invention is best.

Characterizing the Unseen Drama of Analytics

Supply chain fragility and geopolitical instability discussed as background to in-shoring pharmaceutical manufacturing by Dr. Fernando Muzzio, distinguished professor of chemical and biochemical engineering, Rutgers University and Frederic Kahn, VP Sales, Wavelength Pharmaceuticals. This discussion covers reforming regulations and economics, while introducing novel flow chemistries, robotics, digitalization, and a heightened agility for investment in education, national strategy and communications.

 presents the Drug Solutions podcast, where the editors will chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products.

Podcasts

In this episode of the Drug Solutions Podcast, Chris Spivey, Editorial Director talks about the economic and geopolitical benefits of controlling pharmaceutical manufacturing through reshoring, with Dr. Fernando Muzzio, distinguished professor of chemical and biochemical engineering, Rutgers University and Frederic Kahn, VP Sales, Wavelength Pharmaceuticals

Drug Solutions Podcast: Securing Manufacturing Independence Through Re-shoring Facilities to USA

In this episode of the Drug Solutions Podcast, Chris Spivey, editorial director, and Meg Rivers, senior editor, interview Sean Tucker, PhD, chief scientific officer of Vaxart, on developing oral recombinant vaccines, including developing this type of vaccine and how it differs from injectable vaccines, an inside look into the manufacture for clinical trials, what pathogens oral recombinant vaccines may be a better treatment option for, longevity of protection, and how this type of vaccine could impact the pharmaceutical industry.

In this episode of the Drug Solutions Podcast, Chris Spivey, editorial director, and Meg Rivers, senior editor, interview Sean Tucker, PhD, chief scientific officer of Vaxart, on developing oral recombinant vaccines.

Drug Solutions Podcast: Developing Oral Recombinant Vaccines

In this Drug Digest episode, Chris Spivey, editorial director, and Meg Rivers, senior editor, dive into APIs, excipients, and formulation advances, specifically pairing the right APIs and excipients for optimizing formulations.

Nitin Swarnakar, manager NA applications lab (pharma solutions), BASF

, is a formulation scientist with more than 14 years of combined (academic research/training/industrial) experience and a strong track record of publications primarily focused on various formulation aspects of small, peptide, and protein molecules for oral and parenteral applications.

Gregory Lane, PhD, senior principal investigator, Bristol Myers Squibb

, started working at Bristol-Myers Squibb (BMS) company in the year 2000 as a PhD organic chemist in the small-molecule API process technology department. During that time, he developed scalable syntheses and utilized process analytical technology (PAT) to monitor reactions and crystallizations from the laboratory to the pilot plant. 

Matthias Bucerius, Head of Actives and Formulation, MilliporeSigma, the Life Science Business of Merck KGaA, Darmstadt, Germany

, serves as head of actives and formulation at MilliporeSigma, the US and Canadian life science business of Merck KGaA, Darmstadt, Germany. He joined the company in 2004 after working as a strategy consultant. 

Anil Kane, PhD, Global Head of Technical and Scientific Affairs, Pharma Services, Thermo Fisher Scientific

, has more than 25 years of experience in the science and business of taking molecules through the entire drug development process, spanning early-stage development to scale-up and commercial manufacturing and includes technical transfers between global sites and drug life cycle management.

Stephen Hoag, professor and director of the APhL, Dept. of Pharmaceutical Sciences, University of Maryland School of Pharmacy

, oversees project management, provides scientific oversight of projects, and handles client relations. In addition to his academic experience, he has worked for the World Health Organization, 3M Pharmaceuticals, and Abbott Laboratories. 

Ilan Avni, VP BD, marketing, and IP, Wavelength Pharmaceuticals

, has more than 20 years of experience in the global pharma, API, and medical devices industries. Avni has been with Wavelength Pharmaceuticals since 2006 and served in various business development, pipeline, and portfolio management roles. 

This episode of Drug Digest is sponsored by:

Drug Digest is a tech talk video series with the 

 editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products.

: Biopharmaceutical drug development and manufacturing

Automating pharma and biopharma processes

Videos

In this episode of Drug Digest, Chris Spivey, editorial director, and Meg Rivers, senior editor, dive into APIs, excipients, and formulation advances, specifically pairing the right APIs and excipients for optimizing formulations.