spoke with Amy Lavelle, associate director, Bioanalytical Lab, PPD Clinical Research, Thermo Fisher Scientific, about the challenges of performing bioanalytical studies and how contract research organizations (CROs) can help mitigate possible regulatory submission problems.

 What are the challenges in performing bioanalytical studies?

Common challenges include supply chain issues and the availability of proper quality reagents. As science continues to find new modalities for therapeutics, complex molecular structures and delivery systems pose challenges for the development of specific and robust assays. For example, in the cell and gene therapy space, use of adeno-associated virus (AAV) vectors for drug delivery creates complications for immunogenicity assessment due to the fact that pre-existing antibodies to the viral vector make finding negative controls and appropriate cut points difficult. When evaluating low-level biomarkers, highly sensitive assays are required, as the assay range needs to be relative to expected biological concentrations, which requires appropriate reagents and equipment.

: What are some mistakes companies make in performing bioanalytical studies and/or a bioanalytical study program?

 The best way to avoid mistakes is to fully understand regulatory requirements and the appropriate guidance to follow when performing bioanalytical studies. It’s also important to allow sufficient time for the laboratory to develop a robust and validated method intended for sample analysis at the clinical stage. The type of lab compliance and assay validation parameters are key factors in ensuring the data are fully supported for the appropriate regulatory submission. Utilizing a CRO that is experienced with and knowledgeable of agency requirements will help prevent the sponsor from facing any submission issues.

 What kind of data from bioanalytical studies are included in regulatory filings?

This is dependent on the drug and its mechanism of action, the proposed indication, and the phase of the trial. Additionally, it depends upon the history of the data already available on the drug and similar compounds or if the need for the drug allows for alternatives, as is the case with orphan status.

An investigational new drug (IND) filing application to start human clinical trials is used to determine if the proposed drug is reasonably safe to administer to humans. Regulatory agencies will review preclinical data, such as pharmacology and toxicology information, genotoxicity, drug absorption and metabolism, and toxicity of metabolites. The proposed clinical protocol for the trial as well as manufacturing information for the drug is discussed.

Phase I, II, and III clinical trials are performed based on FDA-approved protocols. In order to manufacture and sell the drug, clinical test data and analysis from Phase I–III are used in a new drug application (NDA) to determine if the drug is safe and effective for its context of use and if there are any risks associated with the drug, and if so, that the benefits outweigh any risks.An abbreviated new drug application (ANDA) also may be filed for generic drugs. These data must demonstrate bioequivalency to the original drug.

How are these data compiled and presented to regulators? Is the process different for FDA versus the European Medicines Agency (EMA)?

 For an FDA IND filing, data from animal and in-vitro toxicology and pharmacology studies are compiled with drug manufacturing information and clinical protocols proposed. In addition, available clinical testing or data from foreign countries may be included. A pre-IND meeting with FDA may be conducted to ensure compliance moving forward.

Animal pharmacology/toxicology information includes a summary on pharmacology and drug disposition,pharmacokinetic (PK) bioanalytical data, and mechanism of action (MOA) of the drug; a toxicology summary, including toxicology study design, findings, and data from toxicology and toxicokinetic studies; a full toxicology data tabulation; and toxicology GLP [good laboratory practice] certification.

For an FDA NDA filing, clinical data from human studies (Phase I–III), which include safety and efficacy results, are compiled and also include drug product control, manufacturing, and stability data. For an ANDA, bioequivalence results also are required.

While the United States has one main body governing drug approval, Europe has multiple agencies, including the EMA, the Committee for Medicinal Products for Human Use (CHMP), and various national health agencies. There are also multiple registration processes in Europe, including centralized, decentralized, mutual recognition, and national. There is a two-step process similar to the US, which includes the clinical trial application, approved at the member state level, and the marketing authorization application, which is approved at the member state and/or centralized level.

Are data from bioanalytical studies a factor in post-marketing of approved drugs?

Yes, post-marketing studies are often important for optimizing the drug’s use. For instance, drug-drug interactions, dose response, or safety studies and mortality/morbidity studies. Other post-marketing studies may be requirements set by FDA (post-marketing commitments) to further monitor and characterize the drug’s effects and safety, such as in subpopulations.

 What are the benefits of outsourcing bioanalytical studies?

 The benefits depend on the needs and resources of the sponsor. These benefits can include, but are not limited to, laboratory resources including technology, expertise, and experience; regulatory knowledge; end-to-end support from trial design to analysis to regulatory submission; dedicated support groups such as quality control, quality assurance, data management, report writing, and statistical analysis; and time/cost savings. Outsourcing frees up internal resources for alternative needs and enables sponsors to work with limited dedicated internal personnel. Capacity and capabilities are often drivers for outsourcing.

 How can sponsor companies and CROs work together to gather and present these data to regulators?

CROs can work with sponsors to ensure appropriate regulatory guidance and testing are being followed for data submission, as well as to help to ensure data and reports are compiled in an appropriate format for submission. CRO labs are subject to audits by FDA, and they often have experience in their interactions with regulatory agencies that can benefit the sponsor. Some CROs have regulatory compliance staff to work with the sponsor as they design and execute their trials.

Articles

Features

A thorough understanding of both regulatory requirements and study challenges can help develop and validate the appropriate methods for a bioanalytical study program.

Aiding Regulatory Submissions Through Robust Bioanalytical Studies

Time-to-market remains a significant factor in drug development today, as delays in timelines can often have costly and damaging effects, not only to the drug developer but to the patient. Challenges in the drug development cycle arise early in the drug candidate screening process, but how are industry players using technology to enhance workflows and shorten time-to-market?

The biggest challenges in early-stage drug candidate screening are always the same when referring to small molecules—that is, new chemical entities (NCEs), says Ciriaco Maraschiello, PhD, executive vice-president and global head of drug development at Evotec, a Germany-based life science company. These challenges include safety, bioavailability (in the case of oral dosages), and the translation of both efficacy and safety from pre-clinic to clinic.

Regarding large molecules, in particular monoclonal antibodies (mAbs), translation is still an issue, Maraschiello notes. He further explains that the formulation aspects of large-molecule drug candidates are even more important than with NCEs because of the “commercial decision.” The formulation must be developed in parallel to the lead optimization efforts in the discovery phase for large molecules, with the selected formulation being already established as the definitive formulation at the early stages of development, Maraschiello adds.

“The formulation is indeed an inherent part of the efficacy of a mAb. In the case of [NCEs], it is important to develop formulations that ensure the highest systemic exposure during the ‘pre-IND’ [investigational new drug] phase,” Maraschiello says. The formulation strategy may continually evolve during clinical development; but, in essence, a drug developer must have a definitive “commercial” formulation at the Phase II stage, Maraschiello asserts.

There are several key challenges that are significantly slowing the route to success for drug discovery programs, the first of which is the need to compensate for the high late-stage failure rate of candidate therapeutics, according to Tatiana Tiago, PhD, Creoptix product manager, Malvern Panalytical.

“Several remedial strategies have emerged to drive earlier failure of unfavorable molecules and expanding and improving the starting pool of candidates in order to survive fierce attrition,” Tiago states.

High-throughput screening (HTS) is a prominent example of how the industry is expanding and improving the starting pool of candidates, Tiago explains; but, while HTS has been a staple of the sector for many years and continues to evolve, its full potential is often limited by several hurdles. Tiago explains that a lack of robust and sensitive assays is one hurdle, which is made worse by the fact that many devices sacrifice sensitivity as throughput is increased. Secondly, HTS can still be long and time-consuming, often requiring several weeks to progress from a hit to a lead. Tiago also explains that timelines are further drawn out by complex data analysis.

“Even if all these challenges can be overcome, researchers are often working with poor compound library diversity,” Tiago says. “In exploring HTS approaches, researchers must be careful they are not just expanding their candidate pool with poor-quality, non-viable candidates—all at considerable time and resource costs.”

In one aspect of drug discovery, there is the growth of fragment-based drug discovery (FBDD), which identifies small, low molecular weight molecules or “fragments” that bind weakly to biologically relevant targets, before leads are then “grown” into drug-like compounds, explains Tiago.

“FBDD offers attractive benefits, from requiring smaller starting pools of compounds and unlocking better avenues for lead optimization to being able to address previously intractable targets, such as membrane proteins,” Tiago says. “However, FBDD can have significant hurdles of its own. High temporal resolution is needed for detection, and—with ligand-to-analyte molecular weight ratios exceeding 1000:1—changes are undetectable to all but the most sensitive methods.”

The most common detection technologies, such as surface plasmon resonance and biolayer interferometry, often struggle with these sensitivity and resolution challenges, Tiago asserts. Meanwhile, another challenge has resulted from the move from broad portfolios spanning diverse disease areas to portfolios that are more focused on promising growth areas—for example, immuno-oncology.

“This means organizations now need a deeper knowledge of target disease pathways and disease-appropriate assays. This dovetails with an industry-wide drought of appropriately skilled staff that can operate in niche domains using highly specialized tools and techniques. Without that competence and expertise, the problem of cumbersome data analysis will persist,” Tiago predicts.

In Tiago’s view, one of the most important advancements for drug discovery bioanalytics is grating-coupled interferometry (GCI), which is a relatively new biophysical characterization method for label-free molecular interaction analysis. This method builds on waveguide interferometry, “measuring refractive index changes in an evanescent field resulting from ligand-analyte interactions to determine binding affinity and kinetic rates,” she says.

Tiago argues that label-based approaches to screening, such as the enzyme-linked immunosorbent assay, can also suffer from a high signal-to-noise ratio, which harms the sensitivity of such approaches. Label-free technologies, such as GCI, have been increasingly replacing and complementing label-based affinity screens however, offering better sensitivity as well as being capable of reaching increasingly high levels of throughput, Tiago says.

“Label-free technologies eliminate the risk of label interactions and detects binding events from across the entire sensor surface leading to a greater number of binding events. This, combined with the better signal-to-noise ratio provided by GCI, allows greater sensitivity to detect interactions precisely and consistently. In this way, GCI is also addressing some of the challenges mentioned above,” Tiago states.

Moreover, GCI is also enabling the ability of drug candidates to treat disease targets that were previously considered undruggable, or untreatable, such as membrane protein targets, Tiago adds. “By using a type of microfluidics that doesn’t clog, GCI lets researchers more easily work with unpurified samples, such as those containing membrane proteins,” she says.

Meanwhile, Maraschiello points out that an improved ability to collect and integrate data that support 

 modeling for prediction and selection, which has been bolstered by artificial intelligence, is a key technological improvement. However, the secret to increasing the success of the late discovery stages (i.e., the nomination of a pre-clinical drug candidate [PDC] with the right efficacy and right safety) involves the combination of an appropriate mix of studies pulled together by drug discoverers and drug developers.

“The appropriate screening cascade will create the opportunity to reduce the attrition of the drug candidate during the pre-clinical phase. The same concept applies when the PDC moves into the clinical development phase,” Maraschiello says.

In the clinical development phase, the translational approaches supported by data management and statistics are the key to correctly designing clinical trials with back-and-forth loops between the pre-clinical and clinical phases, Maraschiello adds.

To optimize early drug candidate screening results, goals must be firmly established. For instance,

it must be clear from the start which type of patient population is the target. “From the start” means that, at the very early stages of drug discovery, a clear target product profile and a defined regulatory strategy plan must be in place when an R&D process is started, according to Maraschiello.

From the starting point, a developability assessment must be established, which occurs at the lead optimization stages, where a compound or a series of lead compounds are thoroughly tested for their potential to become a therapeutic product. In the case of advanced therapy medicinal products, market access considerations are even more important and must happen early in the R&D process, emphasizes Maraschiello.

“Consequently, what is important is not the quantity but the quality of the molecules because of an intelligent screening based on the premises mentioned above,” says Maraschiello.

The ideal early screening strategy encompasses two key goals: high throughput and high-quality hits, according to Tiago. Such an approach speeds the route to market in two main ways: by having a larger pool of candidates that can weather later waves of attrition without being fully depleted, and by minimizing the time and resources spent progressing sub-optimal candidates.

The insight needed to drive hit quality requires sensitivity and performance that isn’t available with many current instruments and methods, Tiago points out.

“Extracting such insight at scale generates unfathomable volumes of data that can paralyze analysts,” Tiago states.

GCI helps by providing binding kinetics information in a single method at the initial stages of screening, allowing researchers earlier—and deeper—insight into how the candidate might behave in a biological system. In the end, this process leads to better decision-making and eliminates the need for successive and distinct affinity and assay screens, which can have contradictory results and can be extremely time intensive.

“GCI data analysis is being streamlined with automated platforms to speed analysis while increasing accuracy and reproducibility. These automated tools are tackling the speed-to-market challenge by reducing the impact of skilled labor shortages and mitigating the risk of later-stage issues owing to human error or unreliable analysis results,” Tiago explains.

Successful early candidate screening means the successful nomination of a high-quality pre-clinical drug candidate, emphasizes Maraschiello.

“Quality here is defined as an enhanced probability of success during the pre-IND phase,” Maraschiello says.

Maraschiello explains that when an appropriate screening cascade is conjugated with a late-optimization-phase design to de-risk the selected compounds before they enter the regulatory pre-clinical development phase, the process either ensures the selection of an IND-ready candidate or can lead to the early termination of a selected drug candidate where the impact of cost and time is made clear at the outset. Another important factor in a successful drug candidate screening process is the ability to integrate “development thinking” into the discovery phases and to develop translational approaches aimed at optimizing the clinical trial designs, says Maraschiello. This approach ultimately increases the odds of a successful Phase III clinical trial, Maraschiello points out.

Ultimately, silo thinking and sequential decisional processes within the R&D value chain should be abandoned, Maraschiello states.

“With the technologies at hand and with the multi-disciplinary character of the R&D process, it is increasingly difficult to keep working in data silos either in discovery or in development and between both phases. The R&D process is not a sequential process anymore; it is a virtuous circle going back and forth through the entire value chain to increase the productivity of the R&D process,” Maraschiello says.

Where the drug discovery and candidate screening process was difficult ten years ago, nowadays, the industry has the increased aptitude to manage pre-clinical and clinical data, which creates a powerful translational and predictive process with the sole purpose of reaching the patient faster and better, Maraschiello adds.

Meanwhile, Tiago notes that, aside from quality and throughput challenges, the one thing hurting and frustrating drug developers more than anything else is the late-stage failure of a candidate that has exquisite target activity but which fails due to other attributes, such poor manufacturability or stability.

“While the activity of your candidate at the target is a critical determinant of its therapeutic and market potential, it isn’t the only one. There are many other attributes that need deep and comprehensive consideration—particle size, shape, structure, surface properties, and thermal stability, for example,” Tiago states. These characteristics can impact behavior as diverse as reaction and dissolution, flowability, compressibility, and efficacy, and because of their impact, these characteristics need consideration as early as possible in development.

“In the case of protein-based therapeutics, stability considerations are particularly important. For example, if a protein is structurally unstable, it can undergo conformational changes that reduce binding and therapeutic efficacy. Similarly, colloidal instability within the final formulation of a protein-based therapy can lead to protein aggregate formation, which could impact delivery or even be immunogenic,” Tiago explains.

With such a complex range of attributes to navigate, developers must, therefore, use complementary and orthogonal analytical technologies to provide a full understanding of their candidates. A helpful suite of tools could include dynamic light scattering for colloidal stability evaluation, differential scanning calorimetry for structural stability measurements, and a host of other complimentary techniques, according to Tiago. Planning an orthogonal strategy is another challenge in and of itself, however. Considerations for an orthogonal strategy include:

Which instruments are best for measuring which attributes?

Which analyses are needed given the therapeutic modality in question?

How might these evaluated parameters then relate to each other or drive efficacy changes?

Such considerations require a level of knowledge and expertise that spans multiple domains and is, as noted previously, in significantly short supply, Tiago emphasizes. Contract research organizations (CROs), for instance, have been stepping up to support bio/pharmaceutical organizations to navigate these key questions.

“Essentially, [CROs] are filling the industry void of specialized expertise and concentrating it in a manner that can best support drug developers. Analytical instrument providers are also helping here, providing timely and extensive advice on optimal study design and being open about the need for orthogonality in early screening. This combination, ultimately, creates a more collaborative environment—one that is carving a smoother, more strategic path to drug discovery success,” Tiago concludes.

An early drug candidate screening strategy should incorporate clear targets to lessen late-stage failure.

Using a Drug Candidate Screening Strategy to Mitigate Late-Stage Risk

Avance Clinical, an Australia-based contract research organization (CRO) for biotechs, announced on Sept. 6, 2022 that it has expanded its services into North America with the acquisition of C3 Research Associates, a US-based CRO partner company. The acquisition will enable Avance to offer biotech clients an easier transition from early phase to later phase studies.

With the acquisition, Avance will have the capability to progress early phase studies in Australia and New Zealand into the United States, allowing biotech clients to continue their clinical development programs while retaining the same CRO services. This efficiency would reduce time and cost and allow for biotech companies to deliver quality data that will be acceptable to FDA.

The company intends to make significant investments in its US operations, including growing its team to more than 120 people and leveraging deep industry experience across a broad range of therapeutic areas, specifically oncology, according to a company press release.

“Avance Clinical has been working with C3 Research Associates in recent years, and they share a similar culture and focus on customer service and clinical excellence. This strong relationship made C3 Research Associates a natural acquisition choice for Avance Clinical’s expansion plans into North America. The due diligence process has taken more than [six] months, and we are excited to now welcome our US team and offer the GlobalReady model for our clients,” said

Yvonne Lungershausen, CEO of Avance Clinical, in the press release.

News

Avance Clinical’s acquisition of C3 Research Associates expands its CRO services to North America.


Avance Clinical Acquires C3 Research Associates

ElevateBio, a biotechnology company specializing in cell and gene therapies, recently announced a long-term strategic partnership with the University of Pittsburgh to accelerate the development of innovative cell and gene therapies. Under the agreement, ElevateBio will locate one of its next BaseCamp process development and good manufacturing practice manufacturing facilities, the Pitt BioForge at Hazelwood Green, in Pittsburgh.

According to an Aug. 25, 2022 company press release, the new facility will be equipped with gene editing, induced pluripotent stem cell, cell, vector, and protein engineering capabilities. The university was awarded a $100 million grant by the Richard King Mellon Foundation in November 2021 to support creation of the facility. The facility is expected to generate 170 full-time jobs, 900 construction jobs, and 360 off-site support jobs.

“This announcement supports the region's rise as a leader in cell and gene therapy and advances our vision of bringing an entirely new commercial manufacturing sector to the area," said Patrick Gallagher, chancellor, University of Pittsburgh, in the press release. "The University of Pittsburgh is proud to partner with ElevateBio in this work, which will see us leveraging lessons from the lab—in new and exciting ways—for the benefit of human health.”

“To realize our vision of transforming the cell and gene therapy field for decades to come, broadening our footprint across metropolitan areas is a key priority for us, and we are thrilled that the University of Pittsburgh will be home to one of our BaseCamp facilities,” said David Hallal, chairman and CEO, ElevateBio, in the press release. “We’ve identified Pittsburgh as an ideal location to extend our BaseCamp presence as it sits at the intersection of science, technology, and talent. We are grateful for the support of the Governor and County Executive as we bring the first-of-its-kind offering we have built at ElevateBio BaseCamp to advance the work of the entire biopharmaceutical industry.”

In partnership with the University of Pittsburgh, ElevateBio will open its next manufacturing center in the city.

ElevateBio and the University of Pittsburgh Announce Creation of Pitt BioForge BioManufacturing Center

Lonza announced a collaboration with Touchlight, a biotechnology company specializing in enzymatic DNA production, on Sept. 6, 2022. Under the collaboration, Lonza will integrate Touchstone’s differentiated source of DNA in its messenger RNA (mRNA) therapeutics and vaccines, while Touchstone will widen the reach of its novel doggybone DNA technology.

According to a company press release, Touchlight’s enzymatic DNA technology is a linear, covalently closed DNA vector. It is produced through an enzymatic manufacturing process, which is designed to maximize speed, scale, and purity. This technology presents an alternative to working with plasmid DNA when working with Lonza’s mRNA manufacturing offering.

“The strategic collaboration with Touchlight enables Lonza to further enhance its position as a global leader in mRNA manufacturing,” said André Goerke, vice-president and business unit head, mRNA, Lonza, in the press release. “We can now provide our customers with a strong foundation to deliver an end-to-end offering that includes access to a novel synthetic DNA technology. Such an integrated solution can prove beneficial in speeding up time to market, which is critical in the fast-paced industry of mRNA manufacturing.”

“We are delighted to provide Touchlight customers the benefits of an end-to-end mRNA offering through our collaboration with Lonza,” said Karen Fallen, CEO, Touchlight DNA Services, in the press release. “Lonza is the leading [contract manufacturing and development organization] in mRNA manufacturing and has an established, global mRNA manufacturing network. The alliance allows both companies to innovate and to extend their offering on a global level.”

Touchlight will expand Lonza’s end-to-end offering for mRNA manufacturing with an additional, differentiated source of DNA raw material.

Lonza and Touchlight Enter mRNA Collaboration

Bio-Rad Laboratories recently introduced a range of type 1 antibodies that are designed to inhibit the binding of evolcumab to its target, human proprotein convertase subtilisin/kexin type 9 (PCSK9). These sequence-defined, recombinant antibodies are intended to develop highly selective and sensitive pharmacokinetic (PK) and anti-drug antibody (ADA) assays for evolcumab and its biosimilars.

Evolocumab is a monoclonal antibody (mAb) that has been used for the treatment of hyperlipidemia, or elevated levels of cholesterol and other lipoproteins. It binds to PCSK9, which, according to an Aug. 25, 2022 company press release, has been shown to play a key role in the regulation of cholesterol levels. By preventing the interaction between PCSK9 and low-density lipoprotein receptors, it intends to reduce circulating cholesterol and other lipoproteins.

This range of five anti-evolocumab antibodies includes fully human immunoglobulin G1 clones and recombinant human combinatorial antibody libraries antibodies with SpyTag (a technology for irreversible conjugation of recombinant proteins) technology incorporated into their heavy chain; this is designed to enable site-directed conjugation or fast-switching to a bivalent Fab or a full-length Ig-like format within an hour. The antibodies can also be used to develop PK bridging, enzyme-linked immunoassays to measure free drug or as a surrogate positive control or reference standard in an ADA assay.

"Bio-Rad's range of ready-made and well-characterized anti-idiotypic antibodies keeps growing, offering researchers enhanced flexibility for the development of custom bioanalytical drug assays against a wide range of marketed biologic drugs,' said Hilary Latham, marketing director, Life Science Group, Bio-Rad, in the press release. "Generated under stringent quality control for batch-to-batch consistency, these antibodies can produce translatable and reproducible results, ensuring assay reliability."

New Technology

Bio-Rad’s new antibodies are designed to develop highly selective pharmacokinetic (PK) and anti-drug antibody (ADA) assays for evolocumab and its biosimilars.

Bio-Rad Launches Anti-Evolocumab Antibodies

Roche recently announced the launch of its first digital polymerase chain reaction (PCR) system, the Digital LightCycler System (DLS). The DLS is designed to detect disease and accurately quantify trace amounts of specific DNA and RNA targets that are not typically detectable by conventional PCR methods.

According to an Aug. 23, 2022 press release, the DLS will allow clinical research to divide DNA and RNA from a clinical sample into up to 100,000 microscopic individual reactions. This provides opportunities for high precision analysis, including identifying ultra-rare targets or accurately quantifying how much of the target DNA/RNA there is at a molecular level.

"Understanding the hidden characteristics of serious diseases is fundamental for ensuring that the most effective treatment is selected for each patient," said Thomas Schinecker, CEO, Roche Diagnostics, in the press release. “The Digital LightCycler System will support clinical researchers and laboratories in identifying rare and emerging disease mutations. This can be instrumental in early diagnosis and therapy decisions."

Roche’s Digital LightCycler System is designed to aid in diagnostics for cancer, genetic disease, and infection.

Roche Launches Digital PCR System

The National Institute of Health (NIH) announced on Aug. 25, 2022, that scientists funded in part by the NIH have successfully generated a mouse embryo model, or embryoid, that develops beyond the formation of the neural tube. Because the model closely mirrors natural mouse embryos 8.5 days after fertilization, this embryoid could potentially be used for research into factors affecting mammalian embryonic development and disease.

According to an agency press release, the researchers combined mouse embryonic stem cells (ESCs) with two types of mouse extraembryonic stem cells that yield the yolk sac and placenta. This enabled development of all brain regions, as opposed to models that just use ESCs. The structure was developed within a yolk sac that formed blood islands, structures designed to support the embryo and its circulatory system. In addition to the neural tubes, a gut tube and precursor cells for sperm formation developed.

The neural tube was flanked by somites, cells that lead to vertebrae, skeletal muscle, cartilage, and so on. The neural tube responded to a developmental challenge in a similar manner to natural mouse embryos. This evaluation was done by depriving the embryo of Pax6, a protein needed for brain and eye development; the resulting neural tubes appeared identical to those that develop in natural mouse embryos lacking the protein. According to the release, the researchers believe that this could be used to explore the genetic and epigenetic factors regulating development, as well as screen for the effects of various chemicals on mammalian embryo development.

This research is being led by Magdalena Zernicka-Goetz, of the California Institute of Technology and University of Cambridge. It is partially supported by Eunice Kennedy Shriver, of the NIH’s National Institute of Child Health and Human Development.

Scientists have developed a mouse model that could be a promising model system for research into factors affecting mammalian embryonic development and disease.

NIH-Funded Scientists Develop Mouse Embryo Model That Generates Neural Tubes

Validair Diamond Scientific (VDS) has invested in a new cleanroom at its Chester-le-Street headquarters. The in-house facility was designed to meet exacting requirements for research and fault-finding, as well as for use as a hands-on training resource.

VDS worked with Total Clean Air to design the cleanroom to be flexible in its performance and functionality, allowing for new experimentation, testing, and training processes. The cleanroom’s control system can be set to underperform, which will make the room fail and replicate real-life critical issues that may arise, allowing the field service teams to develop strategies and resolve these issues. The cleanroom will also be used to conduct research of fault-finding, rectification works, and test methodology comparisons.

"The room was installed in early June and is already helping us to improve procedures, refine techniques, and perform experiments and case studies that support our UKAS accreditation," said Steve Ward, managing director at Validair Diamond Scientific, in a press release.

Validair Diamond Scientific has installed a new cleanroom for in-house testing, research, and training. 

Validair Diamond Scientific Installs New Cleanroom

CYTENA, a BICO group company and supplier of high-precision laboratory equipment for handling biological cells, recently unveiled the next generation of B.SIGHT, a fully automated single-cell dispenser. The B.SIGHT instrument is designed to streamline single-cell isolation in microbiology research, with emphasis placed on handling bacteria, yeast, and other microorganisms.

“The new B.SIGHT brings isolation of bacteria and yeast to the next level,” said Julian Riba, CEO, CYTENA, in an Aug. 8, 2022 company press release.. “This second generation single-cell dispenser is really the outcome of a great collaboration between our team and our customers.”

“The new instrument provides more automation, faster processing speeds, higher resolution, and precise dispensing,” said Hussein Hamzeh, the product manager in charge of B.SIGHT, in the release. “Researchers using the B.SIGHT not only will be able to accelerate microorganism isolation workflows but also significantly reduce plastic waste.”

CYTENA’s B.SIGHT cell dispenser is designed to streamline single-cell isolation in microbiology research.

CYTENA Unveils Fully Automated Single-Cell Dispenser for Microorganisms

New England Biolabs (NEB), a supplier of enzymes for molecular biology applications, announced the release of the Faustovirus Capping Enzyme (FCE), a messenger RNA (mRNA) capping solution, on Aug. 9, 2022. FCE is designed to improve capping efficiency and scalability for mRNA manufacturing workflows, including vaccine generation.

FCE is a single-subunit enzyme that contains the enzymatic activities to achieve a Cap-0 structure, which is necessary in eukaryotic mRNA maturation. According to a company press release, FCE is active over a broader temperature range (20 °C–55 °C) than traditional enzymatic capping approaches and demonstrates increased capping efficiency across a variety of mRNA 5´ structures.

"The biological versatility of mRNA continues to propel its rise as a therapeutic modality within infectious disease, oncology, and beyond," said Breton Hornblower, product portfolio manager, NEB, in the press release. "We are very excited to introduce FCE—an enzyme discovered at NEB—to our portfolio of products for mRNA synthesis. This new product offers a streamlined, scalable, and cost-effective solution for mRNA capping for both research and therapeutic applications."

"For large-scale mRNA production, I have always favored post-transcriptional enzymatic capping due to the significant advantages in terms of yield," said Andrew Geall, chief development officer, Replicate Bioscience, in the release. “This new enzyme with improved activity at lower temperatures promises great utility for the production of our large (9–16 kb) self-replicating RNA vector.”

According to the release, FCE is manufactured through environmentally friendly manufacturing practices, avoids the use of organic solvents and without producing significant volumes of hazardous waste. A good manufacturing practice-grade format of the enzyme will be available in early 2023.

The Faustovirus Capping Enzyme launched by New England Biolabs is designed to increase capping efficiency and scalability of mRNA manufacturing workflows.

BioPharm International's BP Elements, September 2022