In the world of extractables and leachables (E&L), one thing that is nearly guaranteed is that change will happen with the materials used in the container closure system. Management of these changes is the responsibility of the drug product manufacturers.

Changes can be external, where the supplier changes manufacturing, information, or availability of a component. It can also be internal, where the drug manufacturer changes the validated manufacturing process or use of the component. External changes can vary from small manufacturing changes that are within manufacturing tolerances, such as in-process changes to time, temperature, etc., to larger manufacturing changes, such as a site change. Larger or more significant external changes can happen, such as a change in the formulation of the material (e.g., additive change) or stopping the manufacture of that particular material. Internal changes can include changes in contact time with a single-use container or the addition of a second supplier of the material components. These internal or external changes are not an exhaustive list but give a flavor of potential changes that may occur.

Guidance for Industry: Changes to an Approved NDA or ANDA, 

FDA details recommendations to holders of new drug applications and abbreviated new drug applications, specifically on post-approval changes for drugs other than specific biotechnology and specific synthetic biological products (1). This guidance provides recommendations for post-approval changes in:

According to this guidance (1), these changes might require post-approval in accordance with section 506A of the US Federal Food, Drug, and Cosmetic Act and 

These documents outline the classification of a change (minor to major) and the regulatory requirements for handling these different change levels.

A minor change, according to FDA guidance, has “minimal potential to have an adverse effect on the identity, strength, quality, purity or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product” (1).

 Title 21, FDA instructs that the applicant must describe minor changes in the next annual report (2).

In an FDA guidance, a moderate change has “a moderate potential to have an adverse effect on the identity, strength, quality, purity or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product” (1).

Commonly, these changes require that the drug manufacturer submit a supplement called Changes Being Effected in 30 Days (CBE-30). This supplement will include information describing the effects of the change. The drug manufacturer must wait 30 days after submission of the CBE-30 before implementing the change and must not implement the change if FDA responds with a request for more information to support the change.

Finally, FDA states that a major change has “a substantial potential to have an adverse effect on the identity, strength, quality, purity or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product” (1).

These changes require that the drug manufacturer submit a prior approval supplement (PAS). The drug manufacturer must wait for FDA approval of the PAS before implementing the change.

Material changes can have an impact on both product quality and the patient. There are a few well-known examples. The most quoted example was during the period of 1998–2002 when there was an increase in the incidence of antibody-positive pure red cell aplasia in patients receiving subcutaneous administration of EPREX (epoetinum alfa). At the time, two simultaneous changes happened. Firstly, the drug product formulation was changed to include polysorbate 80; and secondly, the coated stopper was replaced with an uncoated one (3). Additional compounds were observed in the leachable analysis of the new product. However, these leachable compounds were only observed when the product contained both polysorbate 80 and used the uncoated stopper, but these new leachable species were not observed when both were used separately.

In the early days of E&L testing, prior to appropriate change management, a change in the composition of the material was first known upon a test being conducted and a new extractable profile—or worse, a leachable profile was observed. Because leachables typically take time to form, this observation implied that a change happened, potentially, many months prior. This first E&L observation was also before the seminal document by the Product Quality Research Institute on 

Safety Thresholds and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products in 2006

(4). This recommendation has set the scene for E&L testing in the years following. Despite this being only a recommendation, it was authored with FDA and Health Canada involvement.

Inhalation aerosols and sprays are deemed to have the highest likelihood of packaging component-dosage form interaction and the highest degree of concern based on the route of administration. As such, it is not too surprising that most of the early work on regulatory requirements focused on orally-inhaled and nasal drug products. It was groups such as the International Pharmaceutical Aerosol Consortium on Regulation & Science that initiated and built on supply chain interaction and understanding. The group’s initial work was published in the 2011 paper, “Recommended Baseline Requirements for Materials Used in Orally Inhaled and Nasal Drug Products (OINDP),” and a subsequent update was provided in 2017 (5).

It is also not necessarily the direct container closure system that can cause problems with patient safety and product quality. Around 2010, there were product recalls due to the wooden pallets on which product boxes were stored. A biocide used to treat the pallets had degraded, and one of its degradants—2,4,6-tribromoanisole (TBA) migrated into the products and tainted them. The TBA has a very low odor threshold, meaning that very small amounts can cause unpleasant musty and moldy aromas. A total of 55 million bottles of Tylenol were recalled in a six-month period in 2010 due to this issue (6). This incident resulted in several pharmaceutical companies ceasing the use of wooden pallets to transport products.

Material changes can have potentially more impact on biologics that are manufactured with single-use systems. A particular biologic can be impacted by small amounts of leachable species. The exact mechanism of this is unknown. The most quoted example of this is “Identification of a Leachable Compound Detrimental to Cell Growth in Single-Use Bioprocess Containers,” a research article by Amgen (7). Researchers found that a trace amount of a breakdown product of a common antioxidant, Irgafos 168, was detrimental to cell growth. The level of this antioxidant was far lower than typical screening levels that would be required due to typical toxicological concerns.

Additionally, it is well known that biologics/peptides are at significant risk from reaction with E&L. The biggest risk relates to covalent bond formation for which there are several well-known examples. One example includes the reaction of the common leachable from halo butyl rubbers. This leachable, the C

2 reaction with the protein, forming a new chemical species.

Acrylic acid, which can be used as the glue in syringes, is known to modify peptides either through the lysine side chain or through histidine by a Michael addition reaction. The level of modification was reported at 0.2–5% of a range of proteins (8).

Other reactions can happen, such as the Schiff base reaction of breakdown products of butylated hydroxy toluene and acylation reactions (9). It is often observed when materials undergo sterilization, which causes additives, such as antioxidants, to degrade and form potential reaction products. It is important to mention that if these antioxidants were not present, the polymer would very rapidly degrade, and the container closure would no longer be useable. It is, therefore, likely that any changes with materials used with biologics could have a more significant impact on patient safety (either because of safety or efficacy) than those with small molecules or medical devices. Further work is in progress to help identify potential issues with common leachables.

Cumulatively, this leads to the importance of understanding the materials used in container closure systems and manufacturing systems for biologics and peptides to avoid potential issues—rather than solving them after the event. Having appropriate data on materials used for biologics/peptides can assist in reducing the risk of interaction with leachables. Appropriate data includes extractable data obtained from studies that are undertaken on sterilized/treated materials under appropriate extraction conditions (where extractables can be correlated with leachables) with sufficient sensitivity. 

What does the future hold? As mentioned at the start of the article, change is inevitable, but there are some potential new changes coming. There is a push for greener materials and the reduction of single-use plastics. Will the additive packages change to allow polymers to be depolymerized back to the starting monomers so they can potentially be used as virgin materials rather than recycled? It is through an understanding of the likelihood and impact of change that potential patient safety can be understood and mitigated.

Guidance for Industry, Changes to an Approved NDA or ANDA 

 Title 21, Part 314, Vol. 5, Subchapter D (Government Printing Office, Washington, DC), accessed June 2022.
3. K. Boven et al., 

Safety Thresholds and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products 

(Sept. 8, 2006).
5. IPAC-RS, “Recommended Baseline Requirements for Materials Used in Orally Inhaled and Nasal Drug Products (OINDP),” 

(Feb. 9, 2017).
6. G. Miller and E. Teichert, “The Battered Brand: A Tylenol Recall Timeline,” 

67 (2) 123–134 (2013).
8. D. Liu et al., 

Andrew Feilden is the European E&L strategic director for Element.

Articles

Features

A comprehensive understanding of potential material change can mitigate its impact on patient safety.

The Impact of Material Management on Extractables and Leachables

Single-cell technologies are transforming our understanding of human health and disease. Single-cell genomics and transcriptomics are mature disciplines that can be used to study more than a million single cells (1). However, human

biology cannot be understood through the analysis of DNA and RNA alone. It also requires the study of proteins and protein modifications, lipids, and metabolites.

Proteins are biochemically active and also serve as signaling molecules. As a result, it is not surprising that approximately 95% of drugs are targeted at proteins. However, protein molecules cannot be amplified like DNA or RNA to perform single-cell proteomics measurements. Thus, novel and highly sensitive technologies are required that can decipher this complexity at the single-cell level and contribute to our understanding of emergent issues surrounding health and disease (2).

Protein function is frequently modulated through post-translational modifications, such as phosphorylation and ubiquitylation, that can change the functional course of the cell with fast kinetics. Processes such as endogenous proteolysis and glycosylation are known to play a role in oncological mechanisms (3,4). In addition, gene expression is affected by so-called bursts in expression, which results in additional variations that would be automatically normalized by post-translational regulatory processes in the case of proteins (5). Furthermore, alternative splicing of RNA transcripts can result in additional protein variants. Single-cell proteomics technologies are now entering the mainstream thanks to the pioneering work of a relatively small group of dedicated scientists and the emergence of extremely sensitive mass spectrometers. Typical estimates of the protein content of individual cells are in the order of 200 picograms (which is one-billionth of a milligram). In a recent study, qualitative and quantitative information for up to 1400 proteins was obtained from single cells using an unbiased single proteomics approach that did not require complex isobaric labeling chemistries to boost the peptide signals (6). Cluster analysis of the data could distinguish cell types and cell cycle stages, despite the technology not specifically targeting known and verified markers.

This microheterogeneity in seemingly homogenous cell populations plays a key role in decisive pathways pursued by biological systems. The underlying microheterogeneity is caused by variations in genes and their expression, and understanding these variations at the single-cell level helps to identify the few cells that act as a seed for cancer development, for example. Studying DNA and RNA molecules within the cell is one of the most common approaches to single-cell biology and has also helped motivate the measurement of proteins at the single-cell level. Exponential advances have been achieved in single-cell DNA and RNA sequencing technologies and, depending on the application, a variety of sequencing techniques can be employed for these studies (2).

With the help of such advanced technologies, studies involving the measurement of the single-cell transcriptomes of more than a million individual cells are now feasible (1) and have revealed previously unseen biology as well as highlighted the heterogeneity of single cells—thereby opening up new areas of biology and medicine. A common enabling factor in all these approaches is the ability to amplify DNA and RNA molecules to virtually any desired amount, bringing these molecules into a detectable or quantifiable range (7).

Unbiased proteomics of single cells have been performed in recent years by specialized research groups involving nano-fluidics that are not yet readily adopted by the general research community. These applications often focus on minimizing the loss during sample preparation and multiplexing samples to boost signal intensity (8,9). Despite these solutions, however, the field still has need of innovations that can boost the sensitivity of the mass spectrometer.

The development of parallel accumulation and serial fragmentation (PASEF) (10) provided a spectroscopic technique used with liquid chromatography coupled to mass spectrometry (LC–MS)-based proteomics to improve sequencing speed and sensitivity. PASEF makes efficient usage of the ion beam and, together with intelligent precursor selection of ions eluting from a trapped ion mobility spectrometry (TIMS) cycle, achieves rapid MS/MS identification speed. In addition, the ions are focused in space and time within the TIMS cell, resulting in a significant boost in the sensitivity. This enables the analysis of low sample amounts, in the range of low nanogram peptide loads.

TIMS measurements also provide collisional cross-section (CCS) values and separation of isomeric species that are mobility offset but mass aligned and alleviate ratio compression in multiplexed quantification approaches. The introduction of these 4D-proteomics capabilities has bridged the gap between the requirements of the most demanding proteomics approaches—such as clinical research proteomics, companion diagnostics research, and personalized medicine research—and the solutions effectively available on the market.

Next-generation sequencing technologies now represent a multibillion-dollar industry (11) that promises to help deliver personalized medicine and precision therapeutics, which will help tackle complex and heterogeneous conditions, such as cancer and Alzheimer’s disease.

Single-cell protein technologies have the potential to transform our understanding of cell biology at the macromolecular level and answer fundamental questions regarding protein dynamics, cell differentiation trajectories, and mechanisms of disease. These processes act at the nano- and microscopic level but fundamentally influence higher-order macroscopic behavior. Hence, it is vital that these processes are understood at the highest possible spatial resolution.

 566, 496–502 (2019).
2. G. Chen, B. Ning, and T. Shi, 

, April 5, 2019.
3. L.A. Liotta and E.F. Petricoin, 

 116 (1) 26–30 (2006).
4. M.A. Connelly, et al., 

 15, 219 (2017).
5. G.K. Marinov, et al., 

 24, 496–510 (2014).
6. A.D. Brunner, et al., 

 12.22.423933 (2020).
7. C.F.A. de Bourcy, et al., 

 9 (8) e105585 (2014).
8. D.Hartlmay, et al., 

 60, 1–9 (2021).
10. F. Meier, et al., 

 17 (12) 2534–2545 (2018).
11. Markets and Markets, 

Single-cell Analysis Market by Cell Type (Human, Animal, Microbial), Product (Consumables, Instrument), Technique (Flow Cytometry, NGS, PCR, Microscopy, MS), Application (Research, Medical), End User (Pharma, Biotech, Hospitals)—Global Forecast to 2026

Gary Kruppa, PhD, is vice-president of Proteomics, Bruker Daltonics.

Innovations in single-cell analytics have advanced the progression of cell biology research, which has brought new understanding of disease mechanisms.

Single-Cell Proteomics Enable Advancements in Disease Research

Shimadzu launched its new Nexera XS inert, a bioinert and biocompatible ultra-high performance liquid chromatograph (UHPLC), in July 2022. The system is designed to resolve the most common problems in biopharmaceutical analysis, such as the adsorption of target molecules to metal surfaces and mobile-phase corrosion caused by high salt content and extreme pH conditions.

The Nexera XS inert UHPLC resulted from cooperative research done with Yasushi Ishihama, a professor at the Graduate School of Pharmaceutical Sciences at Kyoto University in Japan under the Japan Science and Technology Agency’s Adaptable and Seamless Technology Transfer Program through Target-driven R&D (A-STEP) project from 2017 to 2020. The system features a metal-free sample flow path, which prevents unwanted interaction with biopolymers that are prone to adsorption onto exposed metal sites. Through this mechanism, the Nexera XS inert results in reduced sample loss and excellent peak shape for generating reproducible, high-sensitivity and high-quality reliable data, according to a July 19, 2022 company press release.

Furthermore, all wetted surfaces have been prepared from corrosion-resistant materials, which renders them stable against mobile-phase solvents that contain high concentrations of salts or acids. Nexera XS inert is particularly well-suited for analyzing biopharmaceutical molecules, such as antibodies, peptides, and nucleic acid drugs.

The new system offers the same analytical intelligence features as the other products in the Nexera series as well as the following features:

Unconstrained recovery and sensitivity: in the quantitative analysis of biomolecules, adsorption of the target compound to a metal surface can result in a dramatic decrease in sensitivity. The Nexera XS inert system comprises stainless-steel-casing-reinforced polyether ether ketone (PEEK) tubing, which is a high-performance engineered polymer with mechanical- and chemical-resistance properties. This ensures a system pressure tolerance of > 100 MPa while maintaining a bioinert flow path. The system also includes a ceramic injection needle, which offers metal-free injections and minimized carryover. By preventing adsorption to metal surfaces, the Nexera XS inert system thus achieves much higher sensitivity and better reproducibility than a general-purpose UHPLC system.

Assured reliability and reproducibility: high salt conditions in the mobile phase can result in the corrosion of stainless-steel parts in standard UHPLC systems, but, in the Nexera XS inert system, the wetted surfaces are prepared from highly rust-resistant materials, while still maintaining the high-efficiency flow-path (i.e., 105 MPa). Because of this design, the system remains unaffected by high salt content, ion pairing agents, or extreme pH conditions, ensuring long-term stability and reliable data acquisition.

Clear resolution without restrictions: the system’s ability to resist 105 MPa of pressure means it can use long separation columns packed with small-sized particles, which allows it to achieve ultra-high efficiency in a wide variety of applications. The newly developed PEEK-lined tubing comes with tool-free, finger-tightened fittings, allowing for reliable connections between columns, which enables the system to withstand a pressure of up to 105 MPa without creating any dead volume or risking damage by overtightening. All valves used in the Nexera XS inert system have been designed to inhibit metal adsorption for worry-free switching between multiple columns. This characteristic is useful for method development or for trap-and-elute analysis. An optional pHM-40 offers real-time measurement of the mobile-phase pH during the course of an experiment. This ensures accuracy and traceability, even when running a pH gradient, as used in ion exchange chromatography.

Consumables ideal for analyzing biopharmaceuticals: analyzing biomolecules, such as proteins, peptides and nucleic acids, requires columns with different separation modes. For some samples that are sensitive to metal ions, metal adsorption must be taken into consideration, and an optimal column would address this issue. The columns used in this new system (Shim-pack series of columns) is fitting for the analysis of a wide variety of biomolecules. In addition, adsorption of target analytes in the sample vial can greatly affect the analysis and requires special attention. Furthermore, a low-adsorption polypropylene vial (TORAST-H Bio Vial, Shimadzu) is also most fitting for peptide drug research, while low-adsorption glass vials (TORAST-H, Shimadzu) are suitable for general-purpose analysis.

New Technology

Shimadzu’s new ultra-high performance liquid chromatography system is designed to solve common problems in biopharma analysis.

Shimadzu’s Nexera XS Inert Chromatography System Enhances Biopharma Analysis

Roche launched its Elecsys HCV Duo immunoassay (Elecsys) in July 2022, which is the first available immunoassay that allows for the simultaneous, independent determination of the hepatitis C virus (HCV) antigen and antibody status from a single human or serum sample, according to the company in a July 18, 2022 press release. This assay allows for the detection of the virus in the early stages of infection, or when a patient is recovering from the virus, or when a patient is showing signs of a chronic infection.

Elecsys uses dual detection of HCV core antigen and antibodies. According to the release, this allows it to enable significantly earlier diagnosis of active infection relative to antibody-only assays, as core antigen appears early in an infection and is a marker of ongoing viral replication. Earlier identification can lead to earlier intervention, less burden on the healthcare system, and better outcomes for patients.

“With improved hepatitis screening, healthcare systems have the opportunity to eliminate the disease through improved prevention, testing, and treatment services,'' said Thomas Schinecker, CEO, Roche Diagnostics, in the press release. “The addition of the Elecsys HCV Duo assay to our HCV testing portfolio can help in the fight to eliminate the hepatitis C virus. The launch of this innovative dual antigen and antibody diagnostic test underlines our commitment to support clinicians and their patients in reducing the impact of infectious diseases, where it’s needed most.”

According to the release, 58 million people were living with chronic HCV infection in 2019, but only 21% were aware of it. Additionally, 1.29 million people died of hepatitis C-related causes, such as cirrhosis or liver cancer. No vaccine is currently available for HCV, but effective treatment with antivirals can lead to a cure in 98% of patients.

Roche’s new test is the first available immunoassay that allows for simultaneous, independent determination of the hepatitis C virus antigen and antibody status.

Roche Launches Dual Antigen and Antibody Hepatitis C Diagnostic Test

Discovery Life Sciences (Discovery), a company specializing in biomarkers and biospecimens, announced its acquisition of AllCells, a provider of human primary blood and marrow-based cells. Discovery plans to combine its existing cell and gene therapy products and services with AllCells to create a business unit called AllCells, a Discovery Life Sciences company. AllCells CEO and President Danny Zheng will lead the entity.

“We are very excited to welcome the AllCells team to the Discovery family,” said Glenn Bilawsky, CEO, Discovery Life Sciences, in a July 12, 2022 company press release. “Bringing these two great companies together creates a scalable, end-to-end solution that gives our clients unprecedented access to reliable human cellular starting materials with integrated multi-omic analytic services to support cell and gene therapies.”

According to the press release, the acquisition grants Discovery access not only to their cell supplies, but also starting materials and analytic services to accelerate cell and gene therapy experiences. Additionally, Discovery’s newly acquired FDA-registered donor collection facilities and good manufacturing practice (GMP)-compliant cleanrooms are adjacent to characterization labs; this placement enables immediate processing and cryopreservation.

“We have built our organization to be an extension of our client's supply chain. By offering donor program consulting, high-quality apheresis collections, customization services, and GMP-compliant starting materials, our dedicated team will continue to provide a high-touch, client-focused approach to ensure our clients' needs are met with superior products and services to fit any timeline and on any scale,” said Zheng in the press release. “Our strategy parallels and reinforces Discovery's 'Science at your Service' approach, and our unified offerings will further accelerate our clients' strategic and vital cell and gene therapy programs.”

News

Discovery Life Sciences’ acquisition of AllCells is intended to bolster its cell and gene therapy products and services.

Discovery Life Sciences Acquires AllCells

AstraZeneca is acquiring TeneoTwo and its Phase I clinical stage B-lymphocyte antigen cluster of differentiation (CD) 19/CD 3 (CD19/CD3) T-cell engager, TNF-486, in a deal worth up to $1.26 billion. One hundred million dollars will be paid upfront, with additional payments contingent on achieving various commercial and regulatory milestones. The deal is expected to close in the third quarter of 2022.

According to a July 5, 2022 press release, TNB-486 is designed for B-cell hematologic malignancies, including diffuse large B-cell lymphoma and follicular lymphoma. It is a T-cell engager, a bispecific molecule engineered to redirect the immune system’s T-cells to recognize and kill cancer cells. By binding to CD19, an antigen expressed on B-cells, and the CD3 receptor on T-cells, it activates and recruits T-cells to CD19-expressing tumors. The drug is currently under evaluation for relapsed and refractory B-cell non-Hodgkin lymphoma.

“By redirecting the body’s natural immune response to target B-cell malignancies, TNB-486 alone or in combination with CD20-targeted therapy could potentially deepen clinical responses and improve patient outcomes,” said Anas Younes, senior vice-president, Hematology R&D, AstraZeneca, in the press release. “We believe this innovative molecule, which was designed to optimize the therapeutic window of T-cell activation, will enable us to explore novel combinations that have the potential to become new standards of care in this setting.”

AstraZeneca's acquisition of TeneoTwo will give the company access to its clinical-stage T-cell engager, TNB-486, strengthening their hematological cancer pipeline.

AstraZeneca to Acquire TeneoTwo in Deal Worth Up to $1.26 Billion

Merck, known as MSD outside the United States and Canada, announced a global development and commercialization agreement with Orion Corporation, a Finnish pharmaceutical company. Through this agreement, the companies will work together to develop and commercialize ODM-208, an oral, non-steroidal inhibitor of cytochrome P450 11A1 (CYP11A1) that is currently in a Phase II clinical trial for the treatment of patients with metastatic castration-resistant prostate cancer. By inhibiting CYP11A1 enzyme activity, ODM-208 is designed to suppress the production of all steroid hormones and their precursors that may activate the androgen receptor signaling pathway.

According to a July 13, 2022 company press release, Merck is making an upfront payment to Orion of $290 million for the rights to co-develop and co-commercialize ODM-208, while Orion will be responsible for the manufacture of clinical and commercial supply of the drug. The agreement also covers other drugs in development by Orion that target CYP11A1.

“Targeting CYP11A1 provides a compelling approach to suppressing the production of steroid hormones, a key driver of prostate cancer,” said Dean Y. Li, president, Merck Research Laboratories, in the press release. “We believe ODM-208 has the potential to complement our existing program in prostate cancer and look forward to working with the team at Orion.”

The contract provides both parties with an option to convert the initial co-development and co-commercialization agreement into a global exclusive license to Merck. If this is exercised, Merck would assume full responsibility for all accrued and future development and commercialization expenses associated with the program. In this scenario, Orion would be eligible for various regulatory and sales-based milestone payments as well as double-digit tiered royalties.

Merck, known as MSD outside the United States and Canada, and Orion Corporation are collaborating to develop and commercialize a treatment for metastatic castration-resistant prostate cancer.

Merck and Orion Announce Global Collaboration for Oncology Drug

PerkinElmer announced the addition of the PerkinElmer Flow Cytometry Instrument Concierge Services to its OneSource Laboratory Services portfolio on July 11, 2022. The concierge service is designed to provide biopharmaceutical labs with expert, on-site flow cytometry specialists to help manage instruments and processes, facilitating reduced downtime, increased productivity, and better data integrity and reproducibility.

According to a company press release, the service includes regulatory quality checks on cytometers, instrument cleanings and preventative maintenance, on-site troubleshooting, phone support, and initial repairs. Additional features include:

Instrument and software training and education

“Flow cytometry is an important part of drug discovery labs, but managing this complex technology in-house can be tedious and time consuming, especially for teams that lack expertise in this area or are experiencing high staff turnover,” said Gary Grecsek, vice president/general manager of OneSource Enterprise Laboratory Services, PerkinElmer,in the press release.“With our OneSource Concierge Service for flow cytometry, lab managers and scientists don’t have to spend time managing these instruments and processes and can focus on other critical efforts and discovering new drug candidates.”

The PerkinElmer Flow Cytometry Instrument Concierge Services will provide biopharmaceutical labs with expert, on-site flow cytometry specialists.

PerkinElmer Introduces New Cytometry Management Service

Merck, known as MSD outside the United States and Canada, launched its Merck Digital Sciences Studio (MDSS) in June 2022, which is aimed at enabling the generation of innovative technologies for drug discovery and development.

The objective of MDSS is to support early-stage biomedical startups with direct investment, access to Azure Cloud computing, and opportunities to pilot their respective technologies in collaboration with discovery and clinical scientists at Merck. Merck opened applications on its website for 12 spots for the first MDSS cohort, and applications for startups developing artificial intelligence (AI) and machine learning (ML) will be prioritized, according to a June 29, 2022 company press release. The program currently plans to include six startups at each of MDSS’ Newark, NJ, and Cambridge, Mass., venues.

The MDSS is a collaboration between Merck and the New Jersey Innovation Institute (NJII), a New Jersey Institute of Technology corporation. Investments have come from the Merck Global Health Innovation Fund, Northpond Ventures, and McKesson Ventures. In addition, Microsoft for Startups will provide technology support, including Microsoft 365 and Azure, as well as provide expert business advice and technical support.

Digital technologies have enabled the innovation of biomarkers for use in drug discovery and development, specifically in the areas of target identification, lead discovery, preclinical development, and clinical development. MDSS will allow collaborators to selectively accelerate and pilot novel and innovative digital technologies that strategically align with Merck’s life science research.

“The biopharmaceutical industry has only just started to harness the tremendous opportunity presented by emerging technological developments in AI and ML,” said Fiona Marshall, senior vice-president, Discovery, Preclinical, and Translational Medicine, Merck Research Laboratories, in the company press release. “The MDSS will provide a collaborative and entrepreneurial setting where scientists have access to the tools and expertise to fuel important innovations that advance drug discovery and development.”

“Startups in the biopharmaceutical industry fuel innovation, create high-quality jobs and generate great opportunities for a stronger, more diverse and inclusive life-sciences ecosystem,” said Simon Nynens, CEO, NJII, in the release. “NJII looks forward to providing the programming, coaching, and connections to bring these ideas to life.”

Merck, known as MSD outside the United States and Canada, now offers the Merck Digital Sciences Studio, designed to enable innovative tech for drug discovery and development.

Merck Digital Sciences Studio Supports Early-Stage Startups

NRG Therapeutics, a UK-based neuroscience company targeting mitochondrial dysfunction, and Domainex, a UK-based integrated medicines research service company, have formed a collaboration to develop novel small-molecule, disease-modifying drugs to treat Parkinson's disease, motor neuron disease (MND), and other debilitating chronic neurodegenerative disorders.

Under the deal, Domainex will provide fully integrated lead optimization services, including assay biology and medicinal and computational chemistry, according to a June 30, 2022 company press release. Over the course of a one-year period, NRG Therapeutics is expected to potentially invest more than £1 million (US$1.2 million) in the project. This program follows a £2.68 million (US$3.2 million) early stage Biomedical Catalyst award granted to NRG Therapeutics by Innovate UK.

NRG Therapeutics’ previous work, funded by Parkinson’s Virtual Biotech, the drug development arm of Parkinson’s UK, has resulted in the identification of a series of small-molecule leads that inhibit the mitochondrial permeability transition pore (mPTP), a transmembrane protein in the mitochondrial inner membrane that is critical for cell signaling and regulated cell death. It has been shown that inhibition of mPTP in brain cells has neuroprotective benefits, as demonstrated in several preclinical models of Parkinson’s and other neurodegenerative diseases, according to the press release.

Domainex’s previous work, which has also been funded by Innovate UK, include a project targeting IκB kinase epsilon/TANK binding kinase 1 for treating inflammatory disease.

In their collaboration, NRG Therapeutics and Domainex will carry out an integrated lead optimization program to optimize the pharmaceutical properties of small-molecule mPTP inhibitors. Their ultimate aim is to nominate a pre-clinical candidate for treating Parkinson’s or MND.

“We hope that this program will result in a new treatment for neurodegenerative diseases, such as Parkinson’s, which will ultimately benefit patients who desperately need new treatment options for these devasting disease,” said Tom Mander, CEO of Domainex, in the press release.

“Mitochondrial dysfunction is a common underlying pathology in many degenerative diseases, and there is a substantial body of preclinical data available, which demonstrates that inhibition of the mPTP in the brain prevents neuronal cell death, reduces neuroinflammation, and extends survival in animals. We look forward to working with Domainex to progress the development of these compounds into potentially life-changing medicines,” said Neil Miller, co-founder and CEO of NRG Therapeutics, in the release.

NRG Therapeutics and Domainex aim to develop novel small-molecule drugs to treat neurodegenerative disorders, such as Parkinson’s disease.

Pharmaceutical Technology's In the Lab eNewsletter, August 2022