Feliza Mirasol is the science editor for 

Feliza Mirasol

On Feb. 5, 2024, Novo Holdings, a wholly owned company of Novo Nordisk Foundation and the parent company of Novo Nordisk, announced that it has entered into a merger agreement with Catalent under which Novo Holdings will acquire Catalent in an all-cash transaction. The transaction values Catalent at $16.5 billion.

Under the agreement, Novo Holdings will acquire all outstanding shares of Catalent at a price of $63.50 per share in cash, a premium of 16.5% to the closing price of Catalent’s common stock as of Feb. 2, 2024. The merger is expected to close by end of 2024, pending customary closing conditions. Following the close, shares of Catalent will no longer trade on the New York Stock Exchange, and Catalent will become a private company.

Novo Holdings intends to sell three of Catalent’s fill/finish sites and related assets acquired in the merger to Novo Nordisk shortly after the merger closes. The three sites are in Anagni, Italy; Bloomington, Ind., in the United States; and Brussels, Belgium.

“Over the past several years, Catalent has built a comprehensive end-to-end offering of services and capabilities to drive innovation in the healthcare system and improve patient outcomes. This transaction is a testament to our team’s hard work and dedication to this mission, and I am incredibly excited for this next step in our journey. We look forward to benefiting from Novo Holdings’ significant resources to accelerate investment in our business and enhance key offerings as we continue to offer premium development and manufacturing solutions for pharma and biotech customers,” said Alessandro Maselli, president and CEO, Catalent, in a company press release.

“We are excited to partner with Catalent as it enters a new phase of growth and accelerates its mission to develop, manufacture, and supply products that help people live better and healthier lives. With our expertise and track record of investing in high quality life sciences businesses, we believe Catalent is a very good strategic fit … Importantly, our acquisition of Catalent is aligned with our mandate to invest in high quality life sciences companies for the benefit of the Novo Nordisk Foundation’s mission and philanthropic causes,” said Kasim Kutay, CEO, Novo Holdings, in the press release.

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Novo Holdings has entered into a merger agreement with Catalent and will acquire Catalent in a deal valued at $16.5 billion.

Novo Holdings to Acquire Catalent in Deal Valued at $16.5 billion

The current trend in biopharmaceutical development is to place more thorough emphasis on molecule characterization early in the drug development process. Thus, pharmacokinetic (PK) and pharmacodynamic (PD) studies developed during preclinical development are crucial.

Being able to characterize the relationship between PK (i.e., how the body interacts with a therapeutic/drug over the duration of exposure to that substance) and pharmacodynamics (i.e., dose effects) is considered an important tool in the drug discovery and development process. Implementing PK/PD studies in the early phases of drug discovery projects facilitates a successful transition from the discovery phase to the development phase (1).

Importantly, establishing an effective PK/PD study design, analysis, and interpretation allows scientists to:

illuminate the relationship between PK and PD

elevate the understanding of a drug’s mechanism of action (MOA)

identify PK properties for further improvement and optimal compound design (1).

Meanwhile, using a PK/PD modeling approach can increase translation of a compound’s 

 animal studies and improves the transition of study results from the preclinical setting to the clinical setting. In fact, it is the effective translation of preclinical data that is critical for developing the design of appropriate and successful clinical trials (1).

Having a sound understanding of a lead compound’s PK/PD relationship provides a PK basis for what to expect in the therapeutic index of that compound. Having this understanding also aids in the design of proper dose regimens for proof-of-concept studies in the clinical development phases. Important factors to consider for maximizing the use of a rigorous PK/PD analysis include establishing a dataset that adequately captures the following profiles: concentration vs. time and effect vs. time. Furthermore, the following should be incorporated in the PK/PD model:

a fundamental understanding of the biological pathway being agitated

a consideration of unbound concentrations

sound statistical and mathematical output.

The bioanalysis of large-molecule therapeutics (e.g., peptides, proteins, monoclonal antibodies, antibody drug conjugates) is typically conducted in a biological matrix, typically serum or plasma (2). Bioanalysis of large molecules is often performed using ligand binding assays such as enzyme-linked immunosorbent assay (ELISA) or electrochemiluminescence (ECL), or, in some cases, hybrid liquid chromatography-tandem mass spectrometry methods (3). It is important to keep in mind that PK profiles of large-molecule therapeutics differ significantly from small molecules based on the absorption, distribution, metabolism, and excretion of large molecules compared to small molecules. Such differences will affect the PK profile of a large-molecule therapeutic (3).

Modeling approach. Dosing requirements for new large-molecule therapeutics should be assessed early; this early assessment must, therefore, be an integral component of the developability strategy of a drug discovery program. For instance, with early dosing requirement assessments, a developer can evaluate whether an extremely high dose is needed to achieve the targeted pharmacological effect. If so, the developer may consider that it is not feasible to advance a potential candidate to clinical or even commercial stages of development without also developing a high-concentration formulation or else maximizing yield in the manufacturing process (4). The use of mechanistic PK/PD models, therefore, come into play, which use knowledge and available competitor data at the early stage of drug development—including the biophysics of the intended target(s) as well as the physiology of the disease—to rationally inform the drug design criteria (4).

., “[m]echanistic PK/PD modeling links PK to PD through a biophysical description of the therapeutic MOA and relevant target biology” (4). The paper goes on to describe that, with a mathematical description of these key MOAs, mechanistic PK/PD models can then be used to support decisions across the drug discovery and development pipeline.

Mechanistic PK/PD modeling can also be applied to decisions in later stages of drug development. To support later-stage drug development and clinical-stage decisions, mechanistic PK/PD models are dependent on the integration of data from 

 preclinical studies as well as data from clinical PK studies, biomarker evaluation, and response studies. “This approach has improved extrapolation capabilities to predict drug efficacy and safety in humans compared to empirical PK/PD modeling; therefore, it is also commonly used in translational research,” according to Grant 

Thus, mechanistic PK/PD modeling has been shown to successfully guide early drug discovery decisions. This approach allows researchers to define a range of drug properties that are expected to achieve the most robust response with respect to receptor occupancy and/or target engagement. Moreover, mathematical modeling can enable early no-go decisions and facilitates the integration of development considerations into the decision-making process early on that then reduces risk in later stages of the development process. Importantly, mechanistic PK/PD models can be applied to recombinant proteins and peptides, in addition to antibody therapeutics, which is an important factor when working with novel biotherapeutic modalities or with biomolecules that are not yet well understood (4).

Early considerations in the drug development process also include how the potential or selected candidate will be delivered 

 to achieve the desired therapeutic effect. As such, PK/PD studies can also be applied to large molecule drug delivery, and strategizing a formulation and drug delivery method needs to be factored in during the early development phase. The advancement of technologies in the biopharma industry has led to the development of increasingly complex biomolecules and more sophisticated drug delivery systems. This has also led to increasingly complex drug absorption and disposition processes following administration with these drug delivery systems (5).

Because PK/PD modeling allows for the separation of drug, carrier, and pharmacological system-specific parameters, it has been used to improve the understanding of the 

 behavior of these complex delivery systems. Thus, PK/PD modeling helps in the development such drug delivery systems.

However, while PK/PD modeling has been helpful in advancing drug development, it poses several challenges. For instance, assumptions used to simplify the drug delivery process so as to plug into the PK/PD model may not be appropriate for the molecule of the delivery system at hand. To start with, any assumptions used must be reliable, and this requires a detailed understanding of the physiological system and drug delivery system at play. Lacking the relevant information makes it difficult to validate the assumptions at the start (5).

Modeling assumptions are typically based on prior knowledge and experience, and thus having assumptions helps to fill missing pieces in existing information as well as simplifies the understanding of a complex system. Modelers should take heed and acknowledge, however, the limitations of the model. Moreover, development of PK/PD models should be fit-for-purpose.

Extrapolation from animal studies to human studies based on PK/PD modeling is another challenge, particularly when it comes to scaling. Some approaches that have been considered to minimize errors with scaling include (5):

Selecting the appropriate animal species for scaling to humans

Employing allometric scaling using multiple species (to both minimize the error and increase the accuracy of prediction)

Where, for some pharmacological systems, the scaling method from animal to human has already been established, use available prior information.

1. Tuntland, T.; Ethell, B.; Kosaka T.; et al. Implementation of Pharmacokinetic and Pharmacodynamic Strategies in Early Research Phases of Drug Discovery and Development at Novartis Institute of Biomedical Research. 

, 174. DOI: 10.3389/fphar.2014.00174
2. Pacific BioLabs. Large Molecule Bioanalysis. 

pacificbiolabs.com/large-molecule-bioanalysis

 (accessed Jan. 15, 2024).
3. Medpace. PK Studies. 

medpace.com/labs/bioanalytical-lab/pk-studies

 (accessed Jan. 15, 2024).
4. Grant, J.; Hua, F.; Apgar, J. F.; Burke, J. M.; Marcantonio, D. H. Mechanistic PK/PD Modeling to Address Early-Stage Biotherapeutic Dosing Feasibility Questions. 

 (1), 2192251. DOI: 10.1080/19420862.2023.2192251
5. Zou, H.; Banerjee, P.; Leung, S. S. Y.; Yan, X. Application of Pharmacokinetic-Pharmacodynamic Modeling in Drug Delivery: Development and Challenges. 


Volume 48, No. 2
February 2024
Pages 32–33

When referring to this article, please cite it as Mirasol, F.Addressing PK/PD Study Design Early in Development.

Strategizing a PK/PD study approach in early phase development facilitates a successful clinical progression.

Addressing PK/PD Study Design Early in Development

Lonza announced on Jan. 30, 2024 that it has formed a collaboration with Oxford Nanopore Technologies, a provider of nanopore-based molecular sensing technology, to validate—according to current good manufacturing practices (CGMPs)—and commercialize a novel test that accurately determines multiple critical quality attributes (CQAs) of messenger RNA (mRNA) products. According to a company press release, this test is the first-of-its-kind; it directly sequences both the DNA template and the mRNA.

The collaboration aims to address industry and regulatory need for a CGMP-grade common testing method that can simplify and streamline mRNA manufacturing. Under the agreement, Lonza and Oxford Nanopore will focus on adapting the latter’s technology to make it applicable to mRNA production analysis and quality control (QC). The nanopore-based sequencing method makes it possible to use one technology platform to simultaneously measure several quality attributes in mRNA products within the same manufacturing site. Once commercialized, the test aims to substantially shorten analytical testing time and thus reduce the manufacturing timeline for mRNA products.

Through the collaboration, Oxford Nanopore will tech transfer its in-house-developed workflows to Lonza for GMP validation. Oxford Nanopore’s GridION device will be used to generate real-time data and reporting. After validation has been achieved, Lonza intends to include the sequencing technology in its analytical development workflow offering. The company will also support Oxford Nanopore’s efforts to achieve stringent quality requirements for QC compliance. Lonza will pre-validate several CQAs of mRNA products for the novel test at its Geleen, The Netherlands-based analytical development laboratory. Tech transfer will happen at Lonza’s QC laboratories on the same site for CGMP-compliant method validation.

“While the mRNA market is fast-expanding, as a relatively new modality, it still relies on the use of traditional analytical technologies. Faster and more effective mRNA analytics could simplify the regulatory review process and accelerate the development path. This collaboration underlines the commitment of Lonza and Oxford Nanopore to bring innovation to the market. Our shared objective is to simplify testing processes to bring mRNA therapies to market quicker,” said Torsten Schmidt, head of mRNA Business Unit, Lonza, in the press release.

“mRNA technologies have already delivered a profound impact in recent years, and the industry is growing into many novel areas, including personalized cancer vaccines. With Lonza, we are excited to develop an enabling technology by developing the first GMP-grade test to analyze multiple critical quality attributes of mRNA products. Nanopore sequencing offers a transformational new approach with its one-of-a-kind ability to sequence native RNA to deliver robust and accurate testing of multiple critical quality attributes, 

 and with rapid turnaround times. Not only may this help with pandemic preparedness, but it could also be crucial in ongoing R&D advancements for mRNA therapeutics,” said Gordon Sanghera, CEO, Oxford Nanopore Technologies, in the release.

Under a new collaboration, Lonza and Oxford Nanopore aim to commercialize a CGMP-validated test for advanced analysis of mRNA products.

Lonza and Oxford Nanopore Partner on mRNA Analytics

On Jan. 30, 2024, Regeneron Pharmaceuticals (Regeneron) announced the formation of a new R&D unit, Regeneron Cell Medicines, founded on an agreement with 2seventy bio, a US-based immuno-oncology cell therapy company. Under the agreement, Regeneron acquires full development and commercialization rights to 2seventy bio’s pipeline of investigational novel immune cell therapies, in addition to that company’s discovery and clinical manufacturing capabilities.

The financial terms include an upfront payment of $5 million. Regeneron will also pay a single milestone payment to 2seventy bio for the first major market approval of the first approved product. In addition, Regeneron will pay 2seventy bio a low single-digit percent royalty on revenues generated by the products. The transaction is expected to close in the first half of 2024, pending certain closing conditions.

2seventy bio was spun out from bluebird bio in 2021. Prior to the spinout, Regeneron and bluebird bio entered into an agreement in 2018 to leverage their complementary technologies. The aim was to discover novel cell therapy approaches to address cancer. Under that original agreement, Regeneron had the right to opt-in to a co-development/co-commercialization arrangement for collaboration targets. Now, under the new agreement, Regeneron will acquire full development and commercialization rights to 2seventy bio’s preclinical- and clinical-stage pipeline. Regeneron will also assume ongoing program, infrastructure, and personnel costs related to these programs.

Approximately 150 employees will transition from 2seventy bio to Regeneron to continue work on cell therapy programs. These employees will remain in the company’s Cambridge, Mass., and Seattle, Wa., sites. 2seventy bio’s current chief scientific officer, Philip Gregory, will be appointed senior vice-president and head of Regeneron Cell Medicines upon the close of transaction.

The divestment frees up 2seventy bio to focus exclusively on the commercialization and development of Abecma (idecabtagene vicleucel), its B cell maturation antigen (BCMA)-targeted chimeric antigen T-cell (CAR-T) therapy for treating multiple myeloma.

“Together with the [b]oard, we have completed a thorough assessment of our business and strategic options. Based on this process, 2seventy has decided to focus our mission on the growth and success of Abecma,” said Nick Leschly, outgoing chief kairos officer and incoming 2seventy bio board chair, in a Jan. 30, 2024 company press release. “As part of this decision, we will divest our research and development programs, with the majority of our … R&D team transitioning to Regeneron. While the decision to reshape 2seventy was driven by a series of challenging realities, it has resulted in an outcome that we believe is right for patients, employees, and our shareholders.”

“Moving forward, 2seventy will be sharply focused on Abecma, with a streamlined team and a dramatically different cost structure and financial profile,” said Chip Baird, incoming chief executive officer, 2seventy bio, in the press release. “We believe this approach will give 2seventy the financial runway to continue to work closely with our partners at BMS [Bristol Myers Squibb] to support a potential third-line launch of Abecma later this year and a return to growth for the commercial business.”

According to the press release, 2seventy bio’s go-forward organization will include approximately 65 employees, primarily in quality and supporting functions. Through its partnership with Bristol Myers Squibb, 2seventy bio intends to return Abecma to commercial growth in 2024. The company expects a final Prescription Drug User Fee Act action following a planned Oncologic Drugs Advisory Committee meeting on the supplemental biologics license application (sBLA) for Abecma based on a Phase III clinical study (KarMMA-3). If the sBLA is approved, it would expand the therapy’s label into the larger third line setting of treatment.

With the formation of the new R&D unit, Regeneron will assume full development and commercialization rights to 2seventy bio’s preclinical- and clinical-stage cell therapy pipeline.

Regeneron Forms R&D Cell Therapy Unit from 2seventy bio Platform Acquisition

Podcast will give an overview of the biosimilars market. Industry experts will discuss regulatory controls, pricing pressure, the state of the healthcare industry, and other factors affecting the uptake of biosimilars in the market. Manufacturing challenges as well as current and future needs will also be discussed. Experts will also highlight technological innovations, such as digitalization technologies, and their role in facilitating analytical characterization and manufacturing controls for biosimilars.

Zara Bukhari, PhD student, Biochemistry, University of the Pacific, Stockton, California

Zara Bukhari completed a master’s degree in engineering at Birla Institute of Technology and Sciences, India, with an internship at Biocon Biologics, focusing on Semglee (insulin glargine-yfgn). This experience sparked Bukhari’s interest in the pharmaceutical industry. Subsequently, she worked as a bioprocess engineer at Biocon Biologics for six years, contributing to the design of purification platforms for biosimilars and innovator biologics. Notably, she was involved in a validation study leading to the successful biologics license application filing of Ogivri (trastuzumab-dkst), a biosimilar to Herceptin (trastuzumab), offering her insights into regulatory requirements and the biosimilars market. Bukhari is currently pursuing a PhD in biochemistry, specializing in ubiquitin biology at the University of the Pacific, Stockton, Calif. Through her PhD, Bukhari aspires to contribute valuable insights into the role of ubiquitination in regulating the cellular proteome and its broader implications in diseases to advance scientific understanding and potentially aid the scientific community in identifying novel drug targets.

John Gabrielson, Senior Vice-President, Biosimilars, and Head of Business, JSR Life Sciences

John Gabrielson is senior vice-president, Biosimilars, and head of Business for JSR Life Sciences. He is a seasoned executive, company builder, and strategist with nearly 20 years of experience developing biologics. With experience at large and small biotech companies and most recently a leading contract development and manufacturing organization, Gabrielson is now focused on accelerating biosimilar adoption across the industry.

 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.

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In this episode of the Drug Solutions Podcast, industry experts give an overview of the biosimilars market and discuss factors affecting not only their manufacture, but their upstake in the market as well.

Drug Solutions Podcast: The Biosimilars Landscape

Pharmapack Europe announced the winners of the 2024 Pharmapack Awards on Jan. 24, 2024 at the Paris Expo in France. The winners comprised four categories across two dedicated awards: the Health Product Awards and the Exhibitor Awards.

The Health Product Awards are open to the pharma industry as a whole. Winners fell into the categories of “eco-design” and “patient-centric design”. The Exhibitor Awards went to excellence “packaging” and “start-up” innovation. Judges also granted Highly Commended honors to two second-place entries because of the high standards exhibited in the packaging innovation and eco-design categories.

Two of the awards were given for a new injection molding technology designed to use pulp instead of plastics and an innovative dispenser that “revolutionizes the way medications are delivered intra-nasally”, according to a Pharmapack press release. Both were both recognized for their innovative approach to product development. The other awards were bestowed for a system that affords quick and easy administration of combinations of lyophilized injectable drugs and for a mono material, recyclable stick for pharmaceutical products.

The two Highly Commended honors were given for a needleless vial and cap system and a dispenser that offers more precise dispensing.

 Nissha Europe won for developing a pulp-injection autoinjector component, a new injection molding technology that uses pulp instead of plastics. Pulp-injection, used for device components and secondary packaging, mainly uses pulp and starch, which significantly reduces plastic use. In addition, components made using this technology can be recycled within a standard paper recycling system. Due to its rigidity, pulp-injection can also be used for complex designs and high dimensional accuracy.

 Coradin was honored for its GREENIS dispenser, which is designed for the accurate dispensing of serums and creams. The dispenser is made from 75% post-consumer recycled plastic.

Capa Valve Ltd won for its system, the Capa Valve, which allows for the compartmentalization of a standard syringe into a dual-chamber device. The Capa Valve consists of the installation of two small parts within existing standard syringes that are suitable for prefilled applications. According to Pharmapack, there are currently only a few companies that offer dual-chamber syringes for either sequential delivery of liquids or premixing of a diluent and lyophilized drug; this is largely due to cost and perceived complexity of such dual-chamber syringes. The advantage of the Capa Valve system is that it can be produced at a comparatively low cost for any standard size syringe using known fill/finish technology to provide a range of functionality.

 Dr. Ferrer Biopharma, a US-based company specializing in the development of intranasal medication therapies, won for its GentleMist Technology (GMT), an innovative drug delivery device that is expected to revolutionize the way medications are delivered intranasally. The device is designed to offer enhanced comfort, targeted drug delivery, and therapeutic benefits. Because traditional nozzles often generate discomfort and pain due to the pressure exerted during administration, patients often find it difficult to comply with their therapy, adversely affecting the overall treatment experience. GMT addresses this challenge by using advanced fluid dynamics principles and engineering expertise that focus on a more gentle and effective nasal spray nozzle.

 Rotor Print won for its development of a recyclable stick suitable for a wide range of current pharma products and applications. The Pharmapack press release points out that most conventional sticks are composed of three, four, or even five layers of different materials, which typically come in combinations of polyester, aluminum, paper, and polyethylene. As such, these structures cannot be recycled because of the difficulty in separating the different layers. Rotor Print addressed this problem by creating a new stick comprising three same-material layers, making the stick completely recyclable. The new design can also be used in the same processes as current, non-recyclable sticks—meaning laboratories can make a beneficial switch without any significant investment in new machinery. This is Rotor Print’s second consecutive win based on its innovative approach to pharma packaging. In 2023 the company received an award for developing a high grade 100% polyethylene teraphthalate blister that provides an equal barrier to the traditional aluminum lid or polyvinyl chloride.

Klim-Loc Medical was honored for its needleless medical vial, which is the only vial-and-cap system that can be packaged during the fill/finish process and be delivered as a completely needleless package. With its patented composition, the system features a medical-grade polymer-threaded nipple affixed to an elastomer septum. The design requires a simple flip of the flip-off cap and a twist of the Luer-lock (threaded) syringe to gain access to the contents.

“What [is] so impressive about our 2024 winners is that all the entries are advancing technologies that either bring about vital improvements in greener production, or are putting the patient front and center of the development process. I congratulate all our winners on their commitment and contributions to the industry,” said Tara Dougal, content director—Pharma, Informa, in the press release.

The 2024 Pharmapack Europe Award winners include companies involved in ground-breaking innovations in novel drug delivery solutions, reusable connected devices, and recyclable packaging.