Increasing molecular diversity is creating a need for the reinvention of process development and control strategies.

Process Development and Control for New Modalities

A thorough knowledge of both the upstream and downstream processes is required to ensure effective removal of residual impurities in biopharmaceuticals.

Removing Residual Impurities

Pharma companies set goals and adopt more sustainable alternatives.

Consumers Seek Sustainable Products

Learning from early market failures, the biopharma industry has worked to improve the fate of antibody drug conjugates.

Improving the Fate of ADCs

Experts reveal how to identify the “right” biochemical, the process of sourcing biochemicals, sourcing challenges, and what industry professionals should know about the space. 

Upstream Processing: Biochemicals and Raw Materials

Industry experts discuss best practices for certificates of analysis.

The Role of CoAs in Supplier Oversight

Various advances in contamination control are being utilized to reduce the chance pollutants contaminate a drug product.

The State of Contamination Control

Novartis announced on Nov. 7, 2022 that the UK Medicines & Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for Cosentyx (secukinumab) alone or in combination with methotrexate for use in pediatric arthritic conditions. Specifically, the two types of juvenile idiopathic arthritis (JIA) conditions are enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in patients 6 years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy.

JIA is a progressive and debilitating autoimmune condition that is the most common type of arthritis in young people, with around 1,500 new diagnoses in the UK every year, according to a company press release. If left untreated, ERA and JPsA can lead to high levels of pain, joint swelling, and disability, with many young people continuing to have active disease well into adulthood. If properly managed, it is possible for patients to live with inactive disease and prevent the progression of rheumatoid arthritis, including hand, limb, and spine deformities.

“We are pleased to announce the news of marketing authorization for secukinumab in young people living with ERA and JpsA and are delighted that they will now have the possibility of accessing an additional treatment option,” said Marie-Andrée Gamache, country president, Novartis Innovative Medicines UK and Ireland, in the press release. “At Novartis, we are continuing in our aspiration to eliminate the disease burden for every person living with painful and debilitating long-term immunological conditions by leading in the commercial sponsorship of clinical trials and turbo-charging discovery with investments in data and digital technologies.”

Articles

The UK MHRA has expanded the use of Cosentyx for use in pediatric arthritic conditions.

UK MHRA Expands Cosentyx License

Shimadzu, a laboratory instruments supplier, and University Medical Center Göttingen (UMG), announced a collaboration to develop new clinical laboratory methods. The focus of their research will be on using liquid chromatography-mass-spectrometry (LC-MS) for therapeutic drug monitoring (TDM) analysis. The collaboration is being performed under Shimadzu’s European Innovation Center program, which is designed to enable collaborations where outside experts can work with Shimadzu technologies.

According to a Oct. 27, 2022 press release, TDM tests, which measure the concentration of drugs currently in blood, have usually been done through an immunoassay, but LC-MS methods have recently grown in popularity due to advantages in strength and accuracy. However, complexity of sample preparation has prevented widespread adoption.

The collaboration will focus on developing Shimadzu's CLAM-2030, a fully automated sample preparation module for LC-MS. The device functions by placing blood collection tubes in position, wherein the module automatically performs sample pretreatment steps up to LC/MS/MS analysis. The collaboration aims to develop new methods for multiple target groups of drugs, as well as means of switching between these new methods easily and quickly.

The collaboration will see Shimadzu and UMG develop new clinical laboratory methods using LC-MS for TDM analysis.

Shimadzu and UMG Göttingen Enter Analytics Collaboration

MGI Tech, a provider of tools and technology for the life sciences sector, announced the opening of an overseas Customer Experience Center (CEC) in London on Nov. 3, 2022. The second such suite in Europe, the new London site is designed to provide local customers and partners first-hand experience with MGI’s various instruments. The company’s other European site, located in Riga, Latvia, opened its doors in late October.

According to a company press release, the center will be operated by partners from the BRC Genomics Facility at Imperial College, London. In addition to various MGI automation systems, the facility will host the United Kingdom’s first DNBSEQ-G400 sequencer, which is designed to facilitate metagenomic analysis, spatial transcriptomics, microbiome, spatiotemporal omics, whole genome sequencing, whole exome sequencing, RNA sequencing, and more.

“Our new CEC will allow easier access to our cutting-edge technology locally. It will also serve as a hub for visitors to come in and experience MGI’s platforms for hands-on workflow, for our field application scientists to perform experiments for demo application, validation, and field testing, as well as for internal and external trainings,” said Duncan Yu, President, MGI, in the release. “We at MGI are proud to support researchers and partners in the region to develop content with our automation and sequencing platforms.”

“The new CEC is an important link to the local research and diagnostic community, enabling new genomic discoveries and medical advances,” said Yong Hou, General Manager, MGI Europe and Africa, in the release. “It has been wonderful to witness how MGI’s developments are transforming research and diagnostics, and our technology* will continue to empower local customers and partners to serve a greater purpose.”

MGI and Imperial College will jointly operate a CEC designed to provide European customers with first-hand experience with various automation and sequencing instruments.

MGI and Imperial College London Establish Overseas Customer Experience Center in the UK

Scorpion Biological Services, a contract development and manufacturing organization focused on the development of biologic drugs, recently hosted the grand opening of its new San Antonio, TX facility. The new facility is designed for the development and manufacturing of clinical and commercial-scale biologics.

“After more than 18 months of tireless work, preparation, dedication from our excellent team, and support from the San Antonio community, we have finally arrived at this moment where we can cut the ribbon, open our doors, and get to work,” said David Halverson, president of Scorpion, in an Oct. 25, 2022 company press release. “This facility will be at the forefront of American biomanufacturing, developing clinical and commercial-scale large molecules, so we can help our clients bring their biologic innovations from the lab to the clinic and to the patients that need them.”

“This is an extraordinarily exciting milestone for our company,” said Jeff Wolf, founder and chairman, Scorpion, in the release. “Today, we checked off a major milestone with the grand opening of Scorpion’s San Antonio manufacturing facility. It is years in the making, and we are thrilled to get the real work started, right here, right now.”

Scorpion’s new facility is designed for the development and manufacturing of clinical and commercial-scale biologic drugs.

Scorpion Biological Services Opens San Antonio Biologics Facility

Editor of Pharmaceutical Technology Europe

Traditional drug development is costly and time-consuming, with many hours, days, and years spent researching and developing novel chemical entities that, for the most part, will likely fail to get to the commercial finishing line. Repurposing a drug can offer companies an approach to drug development that is much more time- and cost-efficient and offers a higher chance of success. According to research, 30% of repurposed drugs gain approval, which is three times higher than the rate for new drugs (1).

There are three main strategies to repurposing a drug product: determining a novel therapeutic indication for an already known drug (repositioning); developing a new formulation of a drug product (reformulation); and combining two or more drugs that were already being used as single drug products (combination) (2). Despite the various benefits of repurposing existing drug products can offer, each strategy also has certain challenges to overcome that can act as a deterrent to developers.

“Reformulation can be used very effectively to develop improved medicines and treatment options for patients,” confirms Jan Jezek, chief scientific officer of Arecor. “For example, creative formulation can be used to improve the pharmacodynamics and pharmacokinetics of a drug.” Highlighting a specific case of creative formulation, Jezek points to the development of a novel formulation of insulin that has is being developed by Arecor, which accelerates the drug’s absorption post-injection, leading to improved glycemic control.

“Another example benefit of reformulation is to convert a lyophilized powder medicine to stable liquid ready-to-use (RTU) product formats, which are becoming increasingly important to enable fast, safe, and effective treatment of patients,” Jezek continues. “Innovative formulation approaches can also lead to improvement in stability of small- and large-molecule products and enable their use outside the cold chain, which can significantly improve convenience of use.”

Balasubramaniam Jagdish, assistant vice-president, Formulation Development, Bengaluru Site, Recipharm, emphasizes that reformulation can be performed for several key reasons. “[Reformulation] can allow developers to improve the performance and patient centricity of an existing drug. For example, it may be done to create a version of an existing drug that is more convenient and easier to use for the patient, increasing quality of life or boosting adherence and, in turn, therapy success,” he says.

Additionally, Jagdish remarks that reformulation can be used to enhance solubility, to improve absorption, or to boost the stability of a drug product formulation. “In all cases, reformulation can save a considerable amount of time and financial resource compared with the discovery and development of an entirely new chemical entity,” he states.

Moreover, it is possible to use reformulation as a way of extending the line of an older drug product, Jagdish points out. “[Reformulation] offers an opportunity to change an excipient or evolve the manufacturing process to deliver marginal gains in performance or ensure compliance with new regulatory requirements,” he says. “Regardless of the reasons for the reformulation, assessment of the regulatory implications of reformulation is essential.”

First and foremost, Jagdish stresses that it is critical for companies to be aware of the regulatory requirements of the target geography of the reformulated drug product. “There is considerable variation in the regimes in each country, so pharmaceutical companies should evaluate their compliance needs on a case-by-case basis,” he says. “For example, the US Food and Drug Administration (FDA) has published its guidance for industry on Nonclinical Safety Evaluation of Reformulated Drug Products and Products Intended for Administration by an Alternate Route, which can help companies understand the regulatory requirements in the [United States]” (3).

For Jezek, considering the formulation excipients and whether those being used in the reformulated product are indeed approved for the intended use—administration route and desired dosage regimen—is critical. “[Whether or not the excipients are considered novel] impacts the complexity of development as it is necessary to justify the use of the excipients and to demonstrate the safety of the excipients required. Novel excipients will carry a higher regulatory and development burden,” he specifies.

When approaching a reformulation strategy for a drug product, developers should define the target product profile at the outset, Jezek continues. “In other words, the formulation scientist needs to understand the desired stability and other requirements that the products must meet, such as specific impurity levels, to be approved by the regulatory authorities,” he says.

After defining the target product profile, the developer needs to understand the degradation pathways that can potentially impact the stability of the drug product during storage, Jezek adds. Appropriate methods must be established so that any degradation pathways can be measured and understood. “Such methods are often referred to as stability‑indicating methods,” he notes.

“The last challenge, which is most critical for successful reformulation, is to be able to select the right combination of inactive ingredients that will collectively interact with the small- or large-molecule drug in a way that reduces the degradation rate and thus enables the desired product profile,” Jezek confirms.

According to Jagdish, the challenges that pharmaceutical companies need to overcome when approaching a reformulation project depend upon the type of reformulation they are undertaking. “For example, when developing a new formulation of a drug for the same indication, achieving bioequivalence for the new formulation with the existing one poses a significant challenge, because it is no longer a like-for-like comparison,” he asserts.

“Reformulation can also be considered to reduce the size of the dose of a medication, to improve safety profile and patient compliance,” Jagdish continues. “Again, in this case, there is a need to demonstrate that the efficacy of the lower dose is equivalent to that of the already clinically proven and approved higher dose.”

Providing another example, Jagdish points out that when developing a fixed-dose combination therapy from two independently approved drugs, demonstration of the bioequivalence can also be tricky. “Here, in addition to maintaining bioequivalence with the two existing single-dose products, companies have to ensure the compatibility of the two drugs when in the same formulation,” he says.

When reformulating large molecules, Jagdish emphasizes that additional challenges—when compared with those facing small-molecule formulators—need to be addressed. Challenges such as solubility, absorption, and stability, he specifies.

Because large molecules are commonly administered via intravenous injection, it can be desirable and more patient-friendly to reformulate a drug product to be administered in an alternative way. “Often the focus of a change in the route of administration for a biological medicine is to enable a change from a time-intensive intravenous administration to a single subcutaneous injection,” Jezek confirms. “This [change] requires developing a highly concentrated formulation of the product that can be delivered via a small volume in a single injection.”

However, by reducing the volume of injectable product, the viscosity can become problematic. “Challenges that need to be overcome in developing these high concentration formulations is high viscosity (which can make the product too difficult to inject) as well as the propensity of proteins to aggregate (resulting in the formation of particles, which are unacceptable in pharmaceutical compositions),” Jezek explains. “In addition, proteins are subject to chemical degradation such as hydrolytic cleavage or oxidation. Innovative approaches to formulation design are often required to overcome these challenges.”

Yet, there are relatively easier reformulation routes, such as updating the excipients or the manufacturing process to extend the product’s line, Jagdish states. “Reformulation in these cases often simply involve step changes in the production process or the preparation of ingredients to enhance product quality or to improve manufacturing efficiency,” he specifies. “New ingredients are not generally involved, reducing the number of challenges that need to be overcome.”

1. N. Sommerford, “Drug Repurposing Basics,” Blog, IQVIA, May 12, 2022.
2. S. Murteira, et al., 

Nonclinical Safety Evaluation of Reformulated Drug Products and Products Intended for Administration by an Alternate Route

Felicity Thomas is the senior editor for 

Companies need to consider and address formulation challenges to employ a successful reformulation strategy.

Considerations for a Successful Reformulation Strategy

Hanna Jankevics Jones, PhD, is a pharmaceutical segment marketing manager at Malvern Panalytical.

Natalia Markova is principal scientist, MicroCal, Malvern Instruments.

The importance of messenger RNA (mRNA)-based vaccines and therapies in global healthcare is growing, spurred on by the success of Moderna’s Spikevax and Pfizer–BioNTech’s Comirnaty COVID-19 vaccines. Such efforts towards precision medicine, however, come with the challenge of increasing complexity (e.g., compared to small-molecule drugs). This complexity demands drug developers and manufacturers use the right analytical tools to fully understand their products.

Nowhere is this complexity more evident than in the lipid nanoparticles (LNPs) used to encapsulate fragile mRNA cargo. Size, composition, aggregation, surface charge, and structure of LNPs can all have significant effects on a therapeutic molecule’s success; and optimizing one property may come at the detriment of another. These interdependent characteristics can impact stability during production, transport, and storage, or affect the delivery and release of the drug product in target tissues.

Unlike small-molecule drugs or protein therapeutics, which are chemically or biologically synthesized, LNPs self-assemble during the mixing of their component ingredients. These components can include cationic lipids, helper lipids such as distearoylphosphatidylcholine (DSPC), sterols such as cholesterol, and polyethylene glycol-containing (i.e., PEGylated) lipids (

). To ensure drug formulators achieve their final product, they must optimize the ratios of these ingredients and perfect the way in which these ingredients are mixed. 

All figures are courtesy of the authors. 

 Schematic of a messenger RNA (mRNA)–lipid nanoparticle (LNP) complex (4). DSPC is distearoylphosphatidylcholine.

Small batch-to-batch differences in mixing can result in products that have significantly different compositions. Similarly, changes in ingredient flow rates can alter the size of the final product. For example, faster flow rates produce smaller LNPs than slower ones. Throughout process development and optimization, drug manufacturers need to confirm they are producing LNPs consistently and to specification.

Particle size is critical because it has implications for drug function. Particles that are too small may be cleared from the bloodstream by the kidneys before they can take effect, whereas larger or aggregated particles may fail to penetrate cells or could induce unwanted immune responses. Thus, drug developers need to ensure that the LNPs they are producing are the optimal size and that the size distribution (polydispersity) falls within acceptable parameters. Unexpected changes in size or polydispersity could signal problems in manufacturing processes or product degradation.

Another factor crucial to the success of an LNP is stability. Solvents used during production may need to be removed before administering the product to patients. Drug developers, therefore, need to be sure that the product created remains stable in the solvent’s absence. They also need to know that the product holds its structure during transport and storage.

Drug developers must also ensure that LNPs maintain their structure and successfully protect their mRNA cargo until the therapeutic is delivered to the target site in the patient’s body. As such, scientists must analyze LNP performance under conditions that mimic the bloodstream or target tissues as well as inter- and intracellular environments.

The surface charge is another critical factor that dictates how well an LNP functions within the body. For example, while LNPs with a positive charge have been investigated, they can trigger inflammatory responses, inducing problems such as hepatotoxicity (1). Negatively-charged LNPs avoid these toxicity issues; however, this is not the only place where the charge is important. LNPs need to respond to changes in the endosomal pH, often by changing charge, which can influence the endosomal escape of their mRNA payload.

Expanding the use of LNPs from intramuscular injections for vaccines to other applications such as cancer vaccines or gene therapies, in which the LNPs need to enter other cell types, the surface charge can impact the uptake of the LNPs to different cell types (2). Thus, formulators need to monitor surface charge to identify LNPs that can access the target cells. It can also be informative to understand how this surface charge varies across relevant pH ranges.

With such a complex range of attributes to navigate, developers must use complementary analytical technologies to provide a full understanding of LNPs. Fortunately, they don’t need to develop these methods 

. Rather, LNP specialists can tap into the well-established field of lipid-based drug characterization, where proven analytical technologies have long helped ensure product quality and function.

To monitor LNP size and sample polydispersity, LNP specialists can rely on dynamic light scattering (DLS)—whether single-angle or multi-angle (MADLS)—and nanoparticle tracking analysis (NTA). Using these methods, LNPs in suspension scatter laser light as they diffuse through a sample. Changes in the scattering pattern are translated to particle size and size distribution, with larger particles diffusing more slowly than smaller particles.

DLS offers the lowest resolution of particle size determination but gives a good indication of the size of LNPs in a sample. Using back, side, and forward detection angles, MADLS offers a higher resolution than DLS, allowing it to identify additional populations of LNPs that DLS might miss. NTA offers even higher resolution but often requires sample dilution, which can perturb LNP stability. The choice between these complementary techniques depends on factors, such as LNP size and polydispersity, sample heterogeneity, and the questions being asked.

When Pfizer–BioNTech contracted PolymunScientific to scale up the process of producing LNPs for the Comirnaty program, Polymun needed to develop

robust manufacturing processes to support large-scale production (3). Key to this development were analytical methods, including those described in this article, to guide process development and control manufacturing processes. Such efforts allowed the company to confirm batch-to-batch consistency and long-term stability of its liposomal and LNP formulations (

 Analysis showing the size distribution of a lipid nanoparticle preparation to monitor product stability over time.

MADLS and NTA also offer the opportunity to determine particle concentration, which provides quick information on process yield and any potential losses from process steps. Recently, researchers applied these methods to liposome samples and showed that the accessible concentration range for MADLS (108 to 1012 particles/mL) overlapped with and extended that for NTA (107 to 109) (

). MADLS offered a similar range when the method was applied to LNPs.

 Using size-exclusion chromatography–static light scattering (SEC–SLS) to show that the weight fraction (Wt fr) of messenger RNA (mRNA) within mRNA–lipid nanoparticles (LNPs) varies across both a single formulation and between different formulations: (a) mRNA–LNP1; (b) mRNA–LNP2 (4). RI is refractive index.

As pH can differ significantly between production and storage conditions as well as physiological environments, it is vital to monitor surface charge throughout the product’s life cycle. Electrophoretic light scattering (ELS) is a powerful tool that can determine the apparent charge of a particle in different conditions; for example, mimicking a pH range from slightly alkaline blood to the acidic endosome. The obtained surface charge measurements allow developers to balance the needs of product development and long-term storage with the requirements for clinical efficacy, optimizing cellular delivery while minimizing toxicity risks.

Production, storage, and application add temperature stresses to LNPs, which can be investigated using DLS thermal ramp experiments or differential scanning calorimetry (DSC). Thermal ramps use DLS to monitor particle stability over a temperature range, while DSC measures heat uptake or release linked to structural transitions or changes in molecular interactions.

Drug developers can use these methods to examine the thermal stability of both the LNP delivery vehicle and its mRNA cargo. Such information is critical during LNP formulation as developers optimize ingredient combinations to improve stability without negatively impacting efficacy. Furthermore, as the DSC thermogram is also a fingerprint of mRNA and LNP’s higher-order structure, companies can use it to inform the selection of mRNA sequence variants during design stages and to compare different formulations and batches of the LNP product. This detailed characterization helps support intellectual property protection.

A method commonly used to monitor particle size and polydispersity is size-exclusion chromatography (SEC) coupled to static light scattering (SLS) or another detection system. But beyond questions of particle size, developers continue to evolve the applications of SEC–SLS to help answer questions about LNP composition, monitoring not only the lipid complexes but also the mRNA cargo. For example, researchers used SEC–SLS to perform compositional analysis of two mRNA–LNPs (4). Monitoring the concentrations of the mRNA and LNPs across the entire particle distribution, the researchers could determine the relative weight fractions of the components—a measure of therapeutic payload. In both mRNA–LNPs tested, the scientists observed variation in mRNA loading across the population.

SEC–SLS offers analytical insights in minutes, accelerating throughput across development and manufacturing. The analysis also eliminates the need for multiple analytical steps and fluorescent reagents and reduces operator impact on measurement consistency. Although still relatively new to LNP manufacture, compositional analysis has proven vital to other medical applications, such as studies of viral vectors in gene therapy, antibody-drug conjugates, and antibody aggregation.

In the complex world of mRNA-based vaccines and therapies, tried and tested analytical technologies, such as DLS/MADLS, NTA, and ELS, are shining a light on the LNPs that help those medicines survive the journey from lab to factory to cellular site-of-action. Researchers are further augmenting those insights by evolving and expanding the applications of DSC and SEC–SLS to build further a more reliable picture of LNP attributes, improving the chances for project success.

Although individual biophysical characterization techniques provide valuable insights into the nature of LNPs, no single technology can provide a complete picture. Instead, orthogonal and complementary approaches are needed to provide a more comprehensive understanding of the critical quality attributes that define product quality, consistency, and, ultimately, efficacy (

 Proven analytical technologies monitor a range of lipid nanoparticle attributes (4). DLS is dynamic light scattering. MADLS is multi-angle light scattering. NTA is nanoparticle tracking analysis. ELS is electrophoretic light scattering. SEC–SLS is size-exclusion chromatography–static light scattering. DSC is differential scanning calorimetry.

This prospect may be daunting if a company is unfamiliar with some of these techniques. The broad expertise of an analytical partner can, therefore, help in the development of the applications needed to achieve a deeper understanding of LNPs.

 31 (26) 6867–6875 (2010).
2. R. Pattipeiluhu, et al., 

 34, 2201095 (2022).
3. Malvern Panalytical, 

Developing an Analytical Workflow for Nanomedicine and 3rd Generation Vaccine Production at Scale

, Whitepaper (2022).
4. N. Markova, et al., 

Hanna Jankevics Jones, PhD, and Natalia Markova, PhD, are pharmaceutical segment marketing managers at Malvern Panalytical.

An orthogonal approach to lipid nanoparticle analysis is recommended to optimize drug development success.

Taking a Closer Look at Lipid Nanoparticle Characterization

Gerresheimer, a provider of drug delivery systems, and Nelson Labs, a provider of microbiological and analytical chemistry testing, announced a strategic partnership on Oct. 31, 2022. Under the partnership, which is designed to reduce risk and time-to-market for primary packaging solutions for injectables, Nelson Labs will conduct extractables and leachables testing, toxicological risk assessments, impurity identifications, and biocompatibility testing of injectable primary container closure systems or components for Gerresheimer.

“With this agreement, [we] will be able to offer an extended service package to our pharmaceutical and biotechnological customers for their new drug development and product life cycle management,” said Jen-Edouard Rabier, director, Business Development, Gx Biological Solutions, Gerresheimer, in a company press release. We are now able to provide our customers the best selection of primary packaging systems (vials, syringes, and cartridges) made of glass or cyclic olefin polymer (COP) without any concerns about compatibility, stability, or safety of the drug product.”

“I am extremely pleased that Gerresheimer and Nelson Labs have taken this very important step forward in joining our forces to provide customers with stellar testing and expert advice in container/closure qualification,” said Piet Christiaens, scientific director, Nelson Labs, in the release. “This partnership is designed to help the pharmaceutical industry take full advantage of our scientific leadership, unique Compounds Screener Database, personalized support, and other resources that will be offered through this alliance.”

Gerresheimer and Nelson Labs will work together to conduct extractables and leachables testing on upcoming primary packaging solutions.

Gerresheimer and Nelson Labs NV Announce E&L Partnership

Merck, known as MSD outside of the United States, and Veeva Systems, a provider of cloud systems for the life sciences industry, announced a ten-year strategic partnership agreement on Nov. 1, 2022. Under the agreement, which builds on an existing 12-year partnership between the two companies, Merck will take a “Veeva-first approach” to new industry-specific software and data. Veeva will provide Merck with a strategic pricing approach and allow Merck input into their product roadmap.

“I am excited to see our partnership with Merck evolve to this strategic level,” said Peter Gassner, CEO, Veeva, in a company press release. “Our teams share a common passion for the industry and an understanding of strategic partnership. I look forward to seeing what we create together over the coming years.”

“Transforming our digital, data, and analytics capabilities is integral to enabling our global colleagues to deliver on our purpose of using the power of leading-edge science to save and improve lives around the world,” said Robert M. Davis, CEO and president, Merck, in the release. “Our strategic partnership with Veeva expands our capacity to leverage innovative technology and enhances our ability to deliver value to patients and all our stakeholders—this is key to how we measure success.”

Under this deal, Merck, known as MSD outside of the United States and Canada, will select Veeva products for industry-specific software and data.

Merck and Veeva Ink 10-Year Partnership Agreement

Johnson & Johnson (J&J) announced on Nov. 1, 2022 that they are acquiring Abiomed, a US-based medical technology provider specializing in circulatory support and oxygenation, for approximately $16.6 billion. The transaction is expected to close prior to the end of the first quarter of 2023.

Under the transaction, shareholders will be given $380.00 per share in cash, along with one non-tradable contingent value right that entitles them to up to an additional $35.00 per share in cash if certain clinical and commercial milestones are achieved.

According to a company press release, this transaction is designed to broaden J&J’s position in the medical technology field, especially as it concerns cardiovascular care. Abiomed is the owner of the Impella heart pump platform, a breakthrough technology with exclusive FDA approvals for patients with severe coronary artery disease requiring high-risk percutaneous coronary intervention, treatment of acute myocardial infarction, cardiogenic shock, or right-heart failure. In addition to the right to Impella, J&J will acquire Abiomed’s pipeline of upcoming therapies.

“The addition of Abiomed is an important step in the execution of our strategic priorities and our vision for the new Johnson & Johnson focused on Pharmaceutical and MedTech,” said Joaquin Duato, CEO, Johnson & Johnson, in the release. “We have committed to enhancing our position in MedTech by entering high-growth segments. The addition of Abiomed provides a strategic platform to advance breakthrough treatments in cardiovascular disease and helps more patients around the world while driving value for our shareholders.”

“We are pleased to have reached an agreement that reflects the remarkable value Abiomed created with our revolutionary Impella heart pump platform and promising pipeline,” said Michael R. Minogue, chairman, president, and CEO, Abiomed, in the release. “This transaction partners us with an organization that shares our patients-first mindset and creates immediate value for our patients, customers, employees, and shareholders. It will enable us to leverage Johnson & Johnson’s global scale, commercial strength, and clinical expertise to accelerate our mission of making heart recovery the global standard of care.”

Johnson & Johnson’s acquisition of Abiomed, a provider of heart pump technologies, is designed to bolster their position in the medical technology sector.

J&J to Acquire Abiomed for $16.6 Billion

Steriline, a European manufacturer of complete lines for the aseptic processing of injectable products, announced on Nov. 1, 2022, that it will be showcasing a vial filling and capping machine (VFCM100) under double-wall isolator at CPHI 2022 being held in Frankfurt, Germany, on Nov. 1–3, 2022. The VFCM100 under double-wall isolator is a solution developed to increase contract development manufacturing organization (CDMO) production capacity for COVID-19 vaccines.

The machine can reach a production capacity of 6000 pieces/hour, according to a company press release. It was developed for injectable drugs and is equipped with four peristaltic pumps, allowing for potentially an infinite filling capacity and a 100% check-weighing. The machine can handle glass vials from 2 mL to 100 mL, and, with an easy format change, can also handle plastic vials.

Meanwhile, the double-wall isolator guarantees sterility throughout the whole aseptic filling process, protecting not only personnel from contact with the product but also minimizing the risk of product contamination. Once vials are capped, they are moved via conveyor belt into a printer where every cap is marked with the relative batch details for tracking purposes. An added benefit of the machine are its space-saving sizes, which comfortably fit in the available processing area, according to the press release.

Although an increase in demand for these types of machines has been seen in Europe and other continents, this increase in demand was not due only to COVID-19 vaccines but also to the manufacture of other drugs. As a result, several companies have expressed plans to convert the VFCM100 under double-wall isolator to the production of other products, such as biotech drugs, over the course of the next few years, according to Federico Fumagalli, chief commercial officer, Steriline, in the press release.

Steriline will be exhibiting its vial filling and capping machine (VFCM100) under double-wall isolator for aseptic filling at CPHI 2022 in Frankfurt, Germany, on Nov. 1–3, 2022.

Steriline Showcases Filling Equipment at CPHI 2022

Marina Necdina is a business development manager, former pharma analyst, and research scientist.

Obesity is considered an epidemic of 21st Century. Due to an increasingly sedimentary lifestyle and unhealthy food consumption, obesity affects both adults and children. Weight gain is not just an aesthetics problem; it leads to higher risk for cardiovascular diseases and diabetes. Overall, the potential burden on the healthcare system is multiplying. To date, solutions offered by pharma companies are far from optimal. However, despite insurance opposition, current new medications show more exciting outcomes for weight loss. Can these new drugs be the next blockbusters in the obesity space?

Weight-loss and obesity are one of the most discussed topics in society. It is becoming even more popular due to the fact that the prevalence of this condition is increasing steadily. Statistics from the Centers for Disease Control and Prevention (CDC) show that the prevalence of obesity in the United States increased from 30.5% to 41.9% from 2000 to 2017 (1).

It is also well-established fact that excess of weight leads to other health-related conditions such as heart disease, stroke, and type 2 diabetes. This in turn translates into healthcare costs that are a burden even for developed countries: in 2019 the annual medical cost of obesity in the US was estimated at nearly $173 billion.

Surprisingly, obesity is considered by medical community more of a behavioral problem that can be treated in most cases by diet and exercise. And yet, many people despite being active or eating healthy fail to lose excessive weight. More research shows that genetics, sedimentary lifestyle imposed by our jobs, and age all contribute to difficulties to slim down and reach a healthy weight profile.

This is where weight-loss medicines are coming into play. However, despite years of research, it has become obvious that an effective weight loss drug is not easy to develop; one of the obvious examples being fen-phen. This combination of fenfluramine and phentermine was considered a miracle drug until it was shown to cause heart valve problems causing patient deaths, which led to billions of dollars in lawsuits (2). The drug was taken off the market.

Another example is Xenical prescription (marketed by Roche) (3) and over-the-counter (OTC) product Ali (marketed by GSK) (4). Once again, its side effects (diarrhea, oily stools) were much stronger than its benefits. Many believe that researchers downplayed the frequency of these side effects. Consequently, the market responded and from $600 million sales per year in the end of the 1990s, prescriptions of Xenical declined every year (5).

New weight loss options on the market are Contrave (a combination of antidepressant and anti-addiction drug) that is distributed by Currax and Qsymia marketed by Vivus. Approved by FDA in 2022 (6), Qsymia is a combination of phentermine/topiramate. However, it has potential side effects, while success of the medication in weight loss is not assured.

Currently, the unquestionable leader in anti-obesity market is Novo Nordisk. Wegovy (semaglutide) was approved by FDA in 2021 as anti-obesity drug (7). This glucagon-like peptide 1 receptor agonist is a higher dose of Novo’s successful diabetic drug Ozempic.

Because the drug showed impressive clinical data unlike other options on the market (33% of patients lose more than 20% of their body weight), sales projections for the drug by 2025 are doubled. Just in three month of 2021, it generated more than $100 million and is expected to reach billions in sales in the next five years.

Indeed, Novo Nordisk can be considered an innovator in the weight loss space. Unlike previous medications on the market that target brain functionality in hunger control (Contrave, Qsymia), Novo went for a different route. It works on glucagon-like peptide 1 receptor (GLP1R) responsible for insulin resistance. GLP1R controls blood sugar level by enhancing insulin secretion. Glucagon-like peptide 1 (GLP-1), a gut hormone, is released in response to meal intake stimulating insulin secretion (8).

Initially, Novo developed Semaglutide (Ozempic), which acts like human GLP-1 and increases insulin secretion, thereby accelerating sugar metabolism. Wegovy, a higher dose of the same Semaglutide, seems to control the hunger as well as sugar metabolism leading to weight loss in obese patients.

The idea of GLP1R as a target attracted other pharma. In 2023, Eli Lilly and Company also intends to enter the anti-obesity market. They have developed Tirzepatide, once-weekly glucose-dependent insulinotropic polypeptide (GIP) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. SURMOUNT-1 clinical trial shows that patients can lose more than 20% of body weight, results comparable to bariatric surgery (9).

In May 2022, the company got FDA approval to use Mounjaro (tirzepatide) injections, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Now Eli Lilly and Company is pursuing approval for weight loss. If approved, the company will represent strong competition to Wegovy with a potentially superior clinical outcome (10).

Novo had to revamp its production due to high demand for Semaglutide and some setbacks with manufacturing facilities (11). 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 increasemanufacture of its APIs, while also being able to assemble and package the oral and injectable products (12).

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 (13).

Another outstanding issue is cost of medication to patients. Qsymia is an example; initial sales of the product were disappointing due to the high cost of medication and reluctance from insurance to cover this cost (14). The reason is that many health insurers view obesity treatments as behavioral issue and lifestyle medications. Consequently, they’re unenthusiastic to provide reimbursement.

Even Big Pharma companies such as Novo Nordisk admitted that Wegovy access and reimbursement will be challenging. It is in industry’s interest to move payer perception of obesity: changing it from a lifestyle issue to a chronic disease. However, one of the pluses of this approach is that clinical benefits for medication such as Wegovy can lead to a reduction in other comorbidities associated with obesity and overall healthcare spending.

Considering that obesity has become an epidemic of the developed world, the earning and growing potential of this market is remarkable. More importantly, obesity treatments can be considered as healthcare preventive medicine.

Nevertheless, drugs like Wegovy or Mounjaro will not solve weight problems for every person. More research shows that metabolism is a complex issue and hunger reduction is not the only approach to treat patients. Research on “brown” fat, leptins, adiponectin, and other fat/sugar processing mechanisms suggests that weight gain is a complicated topic (15).

Despite headwinds, obesity drugs are obviously making an impact in the pharma markets.

D.J. Morrow, “Fen-Phen Maker to Pay Billions In Settlement of Diet-Injury Cases,” 

Mayo Clinic, “Alli Weight-loss Pill: Does it Work?”, Mayoclinic.org, March 12, 2022.

R. Robbins, “A Popular Weight-loss Pill was Buoyed by Studies that Understated its Harms,” 

Vivus, “FDA Approves QSYMIA for the Treatment of Obesity in Adolescents Ages 12-17,” Press Release, July 20, 2022.

FDA, “FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014,” Press Release, June 4, 2021.

Eli Lilly, “Lilly's Tirzepatide Delivered up to 22.5% Weight Loss in Adults with Obesity or Overweight in SURMOUNT-1,” Press Release, April 28, 2022.

Eli Lilly, “FDA Approves Lilly's Mounjaro (tirzepatide) Injection, the First and Only GIP and GLP-1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes,” Press Release, May 13, 2022.

Novo Nordisk, “Novo Nordisk Announces Supply Challenges for Wegovy in the US,” Press Release, Dec. 17, 2021.

Novo Nordisk, “Novo Nordisk Invests More than DKK 17 bn in Expansion of the Manufacturing Facilities in Kalundborg, Denmark,” Press Release, Dec. 12, 2021.

Eli Lilly, “Lilly Plans to Invest $2.1 Billion in New Manufacturing Sites in Indiana,”Press Release, May 25, 2022.

DietsInReview, “Qsymia Sales Prove Disappointing Thus Far,” 

H. Wein, “How Brown Fat Improves Metabolism,”

New medications show exciting outcomes for weight loss.

Are Obesity Drugs the Next Blockbusters?

Lonza and Singzyme, a biotechnology company specializing in developing enzymes for protein ligation, announced a strategic collaboration on Oct. 31, 2022. The goal of this partnership is for the companies to use Singzyme’s enzymatic conjugation platform to develop novel bioconjugates.

The partnership will grant Lonza access to Singzyme’s enzymatic conjugation platform, which is designed to enable the site-specific binding of payloads with peptidic linkers to proteins of interest. In return, Singzyme will gain access to Lonza’s network and expertise in the development and manufacture of bioconjugates.

“Singzyme’s highly-specific conjugation platform represents an attractive addition to Lonza’s Bioconjugation toolbox that includes protein expression, linker and payload manufacturing, manufacturability assessments, de-risking, and bioconjugation,” said Stefan Egli, vice-president and head of Bioconjugates, Lonza, in the release. “Its implementation into our offering will further increase our bioconjugation repertoire and provide reliable and selective conjugation solutions for our customers aiming to develop novel bioconjugates.”

“The collaboration between Lonza and Singzyme will provide Lonza’s customers with access to a one-stop technology platform allowing for rapid site-specific bioconjugation including dual payloads, with fully controllable drug-to-antibody ratio, while preserving antibody activity,” said Abbas El Sahili, chief technology officer, Singzyme, in the release. “We foresee that this collaboration will significantly shorten the [antibody drug conjugate] development timeline and bring a wealth of novel drugs faster to the clinic for the benefit of cancer patients.”

Lonza and Singzyme will use Singzyme’s enzymatic conjugation platform to develop novel bioconjugates.