Many industries need faster, more sensitive and robust liquid chromatography (LC) methods capable of meeting stringent regulatory requirements. As part of meeting these requirements and ensuring product quality and safety, it is often the case that an LC method must be able to reliably separate and detect all compounds and impurities within a sample. To do this, scientists must complete extensive method development and optimization for different analytes, often across different instruments and laboratories.

Despite advances in LC technology improving analysis speed, however, method development and validation phases still cause bottlenecks that can take weeks or months to complete, especially if there is a need to test and optimize multiple different column sizes. This process requires multiple chromatographic runs to test different parameters, which reduces productivity and increases operational costs. In addition, once optimized for one instrument, methods are often transferred to other instruments within a lab, or to other labs, presenting a new set of challenges in terms of optimization and validation.

Every LC method also needs to be reviewed regularly to ensure that it continues to perform as initially intended. In practice, this is a time-consuming and costly process, requiring multiple experimental runs for each instrument. This article explores how advanced LC technologies can help streamline this task.

Every analytical method has a lifecycle that begins when a method is first developed and validated and continues as the method is verified and modernized to keep pace with technology advances and as new analytical approaches emerge. Method lifecycle management (MLCM) is a control strategy that ensures analytical instruments perform as intended throughout their lifetime.

In an optimal MLCM strategy, effort is invested upfront in building robust methods, resulting in a complete understanding of the method variables and the impact they have on analysis.By doing so, analysts can quickly assess the impact of a mistake or change further down the line.

Taking LC as an example, for any method there is a lifecycle that comprises three main stages: method development, method transfer, and method qualification or validation. In method development, separation parameters are optimized or modernized, ensuring the best techniques and instrumentation are used to properly assess the goal of the analysis, such as detecting impurities within a sample. In method transfer, a method that is optimized on one instrument may be rolled out to other laboratories or multiple instruments/platforms. Finally, in method qualification or validation, the robustness of the method and—if appropriate—its compliance with regulatory standards is assured and monitored long-term.

Automation is often used upfront to develop LC methods. Yet, at each stage in the LC method lifecycle, there is a range of common instrument challenges. The remainder of this article illustrates how advanced technologies can support a robust MLCM strategy.

At the initial LC method development stage, there are several parameters to optimize. These include the mobile phase pH, column chemistry, separation temperature, and the gradient profile.

The mobile phase pH value is paramount when analyzing ionizable compounds and should be optimized for separation target compounds and impurities. This optimization can be particularly challenging for acidic and basic compound mixtures and requires screening of various pH values. Separation may need to be tested on a range of columns because selectivity can vary dramatically between different chemistries. Similarly, the optimal separation temperature should be explored during method development because this can dramatically alter selectivity.

Optimizing all these parameters during method development can require many chromatographic runs. Moreover, users must consider the complex interactions between various separation parameters and then review large amounts of data from multiple runs, testing multiple parameters, to decide on the optimal conditions for their analysis goal. As a result, method development can be a laborious, resource-intensive, and somewhat subjective process for chromatographers.

By contrast, advanced automated LC instruments and software can accelerate method development by offering the potential to screen multiple columns and an extensive range of solvents easily and efficiently. For example, an automated method scouting solution was used to develop an LC method for separating two isomeric forms of budesonide, a steroid used to treat asthma (1) . Through automated switching between port valves, it was possible to scout four columns spanning a broad selectivity range with six different aqueous buffers, from pH 3 to pH 8.

A predefined eWorkflow template with methods for scouting and column switching made set-up easy while also allowing changes to key custom variables such as flow rate and column temperature.

After analysis, advanced LC software objectively selected the optimal run conditions from the test data based on pre-determined criteria for a specific analysis goal—in this case, the ability to resolve a critical peak pair representing the budesonide epimers. In total, it was possible to test 24 different chromatographic conditions in less than 20 hours with a total data processing time of less than one hour, without the need for manual interaction.

For improved separation of the isomers, the optimal separation temperature was investigated using advanced thermostatting options (

). An optimal sub-ambient separation temperature of 10 °C improved the resolution. With advanced LC systems, it’s possible to scout temperature settings while simultaneously using a passive eluent pre-heater for all four columns to avoid any thermal mismatch. 

In conclusion, using an automated method scouting solution with advanced LC analysis software accelerated the method development process for budesonide analysis significantly.

The next stage of an MLCM strategy is method transfer. Instrument-to-instrument transfer of an LC method is a frequent challenge for most analytical laboratories, occurring when methods are rolled out to other laboratories or transferred to additional or more modern instruments. The complexity of the method transfer process will depend on the requirements of the analytical outcome and the defined limits of acceptable deviation. During method transfer, only minimal modifications of method parameters are permissible without the need for time-consuming revalidation. Ultimately, for most laboratories, method transfer is a pain point that can cause delays in the implementation of an analysis method. The technical characteristics of a transferring or receiving system often differ, and even small mismatches between flow path volumes on different instruments can influence peak retention times or resolution, causing inconsistencies in analysis.

Advanced LC systems make method transfer much more straightforward, owing to their ability to adjust parameters flexibly and automatically. This ability removes the burden of manually matching parameters, such as the gradient delay volume (GDV), pump mixing mode, and column and eluent thermostatting options, all of which can influence peak retention times or resolution and need careful attention during method transfer.

One example is the transfer of a compendial method for impurity analysis of the antiseptic and disinfectant chlorhexidine digluconate from one LC instrument to another (2). 

 (top) shows the congruence in the peak area between the two instruments. 

Although the relative retention times were similar, there were small deviations in absolute retention time, with all peaks eluting slightly earlier on the Vanquish Core instrument. To compensate for this, the GDV was fine-tuned on the Vanquish instrument. Analysts can achieve this through two means. First, it is possible to tune the idle volume setting of the autosampler’s metering device within a 230-uL range (the default setting is 25 uL). Second, using an optional method transfer kit, it becomes feasible to insert a 200-uL volume loop into the flow path between pump and autosampler. Together, these adjustments make it possible to tune the GDV to up to 430 uL. In the chlorhexidine example, it was possible to fine-tune the receiving system’s GDVs by increasing the idle volume from default (25 uL) to 200 uL, and this decreased the deviations in retention time for chlorhexidine impurity peaks (

The third stage of a method’s lifecycle is its validation, or qualification, to assure its robustness and compliance with relevant regulatory standards. To validate an LC method, laboratories typically create injection sequences, data processing steps, and reports—all of which can be complex and time-consuming. Moreover, the data processing step is often laborious and error-prone, involving manual or semi-automated export to an external analysis program or spreadsheet.

Using an advanced LC system with an accompanying data management system makes it possible to automate every step of validation. A further advantage is the pre-configuration for regulatory compliance (e.g., with International Council for Harmonisation [ICH]). By contrast, this is not the case for many non-specialized external analysis programs, such as spreadsheets.

The power of this approach is illustrated by the validation of an assay method for acetaminophen based on the 

) and in compliance with guidelines from ICH. (3)

To enable quick and easy creation of injection sequences, it is possible to use a software extension package with predefined eWorkflow templates based on ICH method validation guidelines. Here, the eWorkflow provides pre-populated injection lists with the options to tailor to user needs clearly highlighted.

The injection list was run twice on different days and by several analysts, with one analysis failing the precision test and the other passing it. Six different injection series were run with ±10% variations in temperature and flow rate to find the optimal parameters. Three different options were used to analyze the limits of detection and quantification: signal-to-noise ratio, standard deviation of the blank, and calibration curve.

After following the injection sequences, the next step was to manually adapt the data processing method for each workflow to meet the specific evaluation criteria, such as recovery range. Once this was completed, the data management system automatically generated a report showing the examined validation parameters and whether the method passed or failed—avoiding the tedious step of creating reports manually (

For other tests, such as linearity, results were reported graphically (

Significant time savings were achieved for a comprehensive method validation using the predefined workflows and templates of advanced LC software, compared with conventional validation processes in which every sequence is set up and run individually and analyzed manually.

LC methods in an analytical laboratory must be reviewed and updated regularly to ensure they are fit-for-purpose and remain up to date with relevant regulatory guidelines. MLCM is a strategy to ensure a laboratory’s long-term analytical methods perform as intended throughout its lifetime. A robust MLCM strategy requires analysts to invest considerable time upfront to fully understand how each LC parameter influences analysis and then review the method regularly, but conventional methods of completing these steps are time-consuming, inefficient, and error prone.

Advanced, automated LC technologies and software can reduce the time and resources required to carry out the multiple chromatographic runs needed to evaluate different parameters, making it possible to test various column particle sizes, eluent solutions, and column temperatures in parallel. Combining these automated features with intelligent data management systems can make MLCM easier and faster by using predefined, regulatory-compliant workflows and data processing templates. Together, these technologies will help analytical laboratories get new and modernized methods up and running faster, realizing the full efficiency benefits of advanced high-performance liquid chromatography.

1. Paul, C.; Fabel, S.; Squibb, A. A UHPLC Method Development System for Efficient Scouting of Chromatographic Elution Parameters. 

Thermo Fisher Scientific Technical Note 185. F.

 (2016).
2. Grübner, M. Transfer of a Compendial LC Method for Impurity Analysis of Chlorhexidine from a Waters Alliance HPLC System to a Vanquish Core HPLC system. 

Thermo Fisher Scientific Application Note 73309

 (2021).
3. Grosse, S.; Quinn, S.; De Pra, M.; Steiner, F. Method Validation Based on ICH Guidelines of a USP Assay Method of Acetaminophen. 

Thermo Fisher Scientific Application Note 73374

Jon Bardsley is market development manager, Pharma & BioPharma, at Thermo Fisher Scientific.

Articles

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Advanced LC technologies can streamline the review process for LC equipment maintenance.

Tools and Technologies for Robust Method Lifecycle Management in Liquid Chromatography

Oligonucleotide drug substances generally are unstable at room temperature, and some are also degraded in the presence of certain enzymes. That is why, in part, they are formulated using special delivery solutions such as lipid nanoparticles (LNPs). (These delivery technologies also facilitate entry of nucleotide APIs into target cells.) Degradation can occur via loss of terminal nucleotides or certain functional groups, oxidation, and other mechanisms. Oligonucleotide–oligonucleotide interactions that can occur at higher concentrations are an added concern. These instability issues must be managed throughout the entire manufacturing process.

The challenges are particularly great for messenger RNA (mRNA), which can be degraded by enzymes found commonly in the environment, temperature, and due to the overall shear sensitivity of the long-chained molecule.

Variety of oligonucleotide drug substances

The landscape of nucleotide-based therapeutics is based on more than half a century of research and development in these modalities, according to Julian Mochayedi, strategic marketing manager for mRNA solutions with MilliporeSigma, the Life Science business of Merck KGaA, Darmstadt, Germany. This knowledge translates to the clinic and beyond, with several approved therapeutic products on the market.

The different types of nucleotide-based therapeutics can be broadly classified by the type of nucleic acid, Mochayedi continues, such as those with DNA or RNA as a basis. Alternatively, they can be differentiated by their functional design, which determines the mode of action. “One can cite DNA-based adeno-associated virus (AAV) vectors for gene delivery, antisense oligonucleotides (ASOs), small-interfering RNAs (siRNAs) for gene expression disruption, and most recently, mRNA to express a protein of interest such as for immunization purposes, as the successful mRNA-based COVID-19 vaccines have demonstrated,” he explains.

mRNA instability particularly challenging

DNA-based oligonucleotide drug substances, such as AAV vectors and plasmid DNA, share the relatively stable characteristics of DNA, Mochayedi notes. The stability of shorter chemically synthesized RNAs such as ASOs and siRNA can be improved through chemical modifications during synthesis. Particularly long biologically synthesized mRNA molecules, however, are inherently unstable, and thus require additional management during manufacturing.

All nucleic acid-based platforms, however, must be formulated using delivery technologies that protect the therapeutic from degradation. Unique solutions such as LNPs help ensure stability in the patient setting, API stability and, ultimately, the efficacy of the therapeutic approach.

There are several reasons why mRNA is inherently unstable. The physiochemical properties of single-stranded mRNA molecules that lead to their instability include their very large size, high negative charge, sensitivity to rapid degradation by omnipresent enzymes such as endonucleases, shear sensitivity, and high viscosity through the formation of secondary structures in solution, according to Mochayedi.

Manufacturing strategies for managing mRNA instability

One of the main culprits causing mRNA degradation is the enzyme RNase. Avoiding it is difficult, however, because this enzyme is ubiquitous. “It is very difficult for mRNA to move freely in the environment,” Christian Cobaugh, CEO and founder of Vernal Biosciences, comments. “Extreme precautions must therefore be taken to avoid introducing this enzyme into manufacturing spaces or enclosures,” he stresses. This issue can often, he notes, be a barrier to entry into the mRNA market for laboratories not experienced in mRNA production.

Use of qualified processes, including sterile single-use technology, should be applied to mitigate contamination and carryover of endonucleases, Mochayedi says. Liberal use of RNase degrading chemicals for cleaning equipment surfaces, operator gloves, and so on is also essential, Cobaugh adds.

The instability of mRNA at room temperature creates further challenges, as the time available for holding generated mRNA sequences at room temperature is fairly restricted, according to Cobaugh. The drug substance must be moved seamlessly to downstream purification and formulation or quickly frozen.

“The choice of adopting a seamless manufacturing approach or having unit operations separated by controlled freezing and subsequent thawing steps must be considered early on, as the decision will impact the design and operation of the mRNA manufacturing facility, and once implemented, that design will essentially be locked in,” Cobaugh contends.

“Ideally, it is best to limit the number of freezing and thaw steps, as they can impact the quality of the mRNA drug substance and formulated mRNA-LNP products,” Cobaugh adds. Furthermore, gentle techniques must be employed. Continuous movement of the mRNA drug substance to purification and then LNP formulation avoids all but the final freezing step. “It is possible, though, with the right engineering solutions and validation procedures to surmount the challenges presented by either approach to mRNA manufacturing,” he concludes.

In addition, stringent optimization of reaction conditions and the process parameters for key unit operations, such as the synthesis step (in vitro transcription) and filtration (via tangential-flow filtration), can overcome viscosity challenges and ensure low shear during processing to maintain the stability of the mRNA at each stage of the manufacturing process, Mochayedi remarks. “Bespoke process development and optimization are necessary for each unique mRNA sequence to address and overcome the highlighted challenges,” he concludes.

While the concept of leveraging mRNA for the prevention or treatment of various diseases is straightforward, the safe and effective delivery of these fragile nucleic acids into cells where their message can be translated into proteins has proved to be a huge challenge, Mochayedi observes. “For the COVID-19 mRNA vaccines, the solution to this problem came through the development of LNPs. These particles, typically composed of four different lipids (ionizable lipids whose positive charges bind to the negatively charged backbone of mRNA, pegylated lipids that help stabilize the particle, and phospholipids and cholesterol molecules that contribute to the particle’s structure), provide a protective bubble for the delicate mRNA molecules, enabling their safe and efficient delivery into cells,” he explains.

The structure of the nucleotide API has a strong impact on the selection of the excipients for the formulation. The manufacturing process must, in addition, be highly controlled. “The buffer solution containing the mRNA drug substance used to produce the LNPs is of low pH (typically aqueous sodium citrate) that places additional stress on the nucleotide’s stability, leading to even more rapid breakdown than occurs at neutral or slightly basic pH,” Cobaugh says.

A low pH of approximately 4.5 is needed to ionize the mRNA so that it forms nanoprecipitates with the lipids. The use of stabilizing process aids is, Cobaugh adds, generally avoided because they would interfere with the ionization of the mRNA and could also potentially end up in the product. Most molecules that would stabilize mRNA against pH-mediated degradation would, furthermore, likely be hazardous chemicals.

The key to successful LNP production, therefore, is minimization of the time required for the LNP manufacturing process. That, Cobaugh emphasizes, requires extensive understanding of the process from a quality-by-design basis combined with thorough process validation. “It is absolutely essential to have a deep awareness of what levers can be pulled from both process and engineering perspectives to minimize the time for all aspects of the formulation process,” he states.

With respect to fill/finish of mRNA therapeutics and vaccines, the strategy is generally no different than that of any other biological API, according to Mochayedi. The goal, agrees Cobaugh, is to fill the product—whether drug substance in sterile single-use plastic bags and containers or formulated drug product into sterile glass vials—and then freeze them as rapidly as possible but in a controlled manner. In this case, the challenges are largely engineering and equipment-related.

For storage and shipment of mRNA, the requirement to maintain the cold chain to ensure its stability and integrity all the way to the patient is of utmost importance, Mochayedi says. “Central storage is usually performed at very low temperatures (-80 °C). Similarly, formulations containing nucleotides require shipment at low temperatures, which is typically achieved using dry-ice packaging,” he notes. In some cases, mRNA drug products may require the addition of a cryoprotectant to protect the particles. The adjustment of excipients to protect the nanoparticles may also enable some formulations to be shipped at approximately 4 °C.

The production of mRNA-LNP formulations that are stable at warmer temperatures is a key focus of developers of candidate therapeutics and vaccines. One approach noted by Cobaugh involves the development of higher-quality DNA templates that are free of breaks (commonly referred to as nicks) that result in the shorter, more unstable mRNA sequences. Mochayedi points to new types of modified nucleotides and new capping technologies to physically altered forms of mRNA, such as circular RNA. “These new approaches may overcome some of the stability issues and enable a broader application of mRNA as a technology platform,” he believes.

Lyophilization of mRNA products as an alternative to freezing is the other main area of investigation. “Theoretically, there is no reason why freeze-dried mRNA products cannot be stored at room temperature as long as water is kept out of the storage containers,” Cobaugh says. He notes that there has been preliminary success in this area, and he is hopeful that lyophilization will be applicable for mRNA products in the not-too-distant future.

Mochayedi agrees, noting that significant investigations into formulation optimizations to overcome the ultra-low temperature requirements of mRNA drug products during shipment and storage are underway across the industry, with lyophilization of formulated mRNA-LNPs as an extremely promising alternative for liquid-based products. “The complete drying of formulations afforded by freeze-drying would unlock the possibility of much more easily providing mRNA therapeutics in countries with higher temperatures,” he remarks. 

Cynthia A. Challener, PhD has been a freelance technical writer for over 20 years, leveraging her education from Stanford University (BS) and University of Chicago (PhD) and 10+ years of industry experience. She currently focuses on pharma/biopharma topics, writing technical articles, white papers, blogs, and other content for a variety of clients in addition to contributing regularly to 

Messenger RNA is inherently unstable and thus requires unique solutions to protect its cohesion.

Finding Solutions to Manage mRNA Instability

Getinge, a Swedish medical technology company, announced the launch of the LivitFlex bioprocess control system. The system is designed to help pharmaceuticals and biotechnology products reach market faster.

According to a Dec. 15, 2022 press release, the LivitFlex speeds up development through system flexibility, smart sensor technology, and easy-to-use software functionalities. Additionally, by accessing and controlling multiple controllers from a PC or tablet in a laboratory, users can set up parallel experiments and monitor all data from one central location.

“Combining the flexibility of the Livit Flex controller, the intuitive Livit software, and Getinge bioreactors enables acceleration of R&D processes to make sure that pharmaceuticals and biotech products will ultimately end up faster where they are most needed – with the patients,” said Matthijs Niemeijer, head, Product Management Bioreactor Systems, Getinge, in the release.

New Technology

Getinge is launching Livit Flex, a bioprocess control system designed to help pharmaceutical and biotech products get to market faster.

Getinge Announces New BioProcess Control System

Merck, known as MSD outside of the United States and Canada, and Kelun-Biotech, a China-based clinical-stage biotechnology company that is a holding subsidiary of Sichuan Kelun Pharmaceutical, recently announced an exclusive license and collaboration agreement. Under the agreement, worth up to approximately $9.3 billion, companies will work together to develop seven investigational preclinical antibody-drug conjugates (ADCs) for the treatment of cancer.

According to a Dec. 22, 2022 press release, Merck will receive exclusive global licenses to research, develop, manufacture, and commercialize preclinical ADC therapies, as well as receive exclusive options to obtain additional ADC candidate licenses. Kelun-Biotech will receive $175 million in upfront payments and an undisclosed equity investment. They will also be eligible for up to $9.3 billion plus tiered royalties for any commercialized ADC product, contingent on various development, regulatory and sales milestone, if they do not retain the rights to research, develop, manufacture, and commercialize certain ADCs for mainland China, Hong Kong, and Macau.

“Advances in ADC technologies are yielding a new generation of candidates designed to more precisely target and deliver potent anticancer agents to the tumor site,” said Dean Y. Li, president, Merck Research Laboratories, in the release. “We continue to augment our oncology pipeline and look forward to working with the Kelun-Biotech team to advance these candidates to the patients that need them.”

“The further expansion of our collaboration with Merck provides a strong endorsement for our technology from a leader in the development of cancer treatments,” said Junyou Ge, CEO, Kelun-Biotech, in the release. “We are grateful for our partnership with the Merck scientists.”

News

Merck, known as MSD outside of the United States and Canada, will pay Kelun-Biotech up to $9l3 billion for seven early-stage oncology treatments.

Merck Licenses Kelun-Biotech ADC’s in Deal Worth $9.3 Billion

The year-end, must-pass government funding package includes multiple provisions important to FDA operations and authority, as well as for clinical research sponsors and pharmaceutical manufacturers. The $1.7 billion Consolidated Appropriations Act for 2023 will reshape Medicaid coverage and bolster pandemic preparedness and biomedical research, among dozens of measures involving drug development and regulation, as the legislators added hundreds of provisions sought by specific states and industries, but also left some key measures on the cutting-room floor.

FDA gains a notable funding increase, as well as multiple new policies and programs. The spending package provides the agency with a $6.6 billion total budget, a 6.5%, or $226 million, increase. That total includes $3.5 billion in appropriated funds plus $3 billion from authorized user fees paid by industry. A 

from Senate and House Appropriations Committees specifies that the added funds should be used to help end the opioid crisis, expand foreign drug inspections, fund orphan product development, advance medical device cyber security, and expand agency data modernization, inspections, and other programs. FDA regulation of human drugs will have $760 million in funds, while the budget for biologics is $272 million, as seen in a chart from the 

A leading provision overhauls FDA regulation of cosmetics to enhance product safety. To help states tackle the opioid crisis, the legislation aims to improve access to FDA-approved non-opioid therapies. Generic-drug makers gained provisions that prevent certain actions by brands designed to delay competition from generics and biosimilars. And to enhance diversity in clinical trials, the legislation instructs sponsors to submit “diversity action plans” for late-stage trials. FDA will issue more guidance on that process, hold public workshops on diversity issues, and report annually on progress in this area.

Probably the most high-profile FDA measure reforms the agency’s accelerated approval process. A key provision clarifies that agency reviewers may require that post-approval studies begin prior to product approval, but it does not require FDA to do so. The measure also speeds up the process for withdrawing drugs that fail to confirm anticipated benefits, while stopping short of mandating such action. Sponsors must provide updates on confirmatory trial status to the agency every six months, and a new FDA accelerated approval oversight council will weigh in on policies.

Missing from the massive bill, however, is a controversial provision that would have confirmed FDA authority to regulate diagnostic tests developed in clinical labs, including those at hospitals and academic medical centers. Although medical device makers and federal regulators backed the change as a way to clarify FDA authority in this area, the proposed VALID Act (Verifying Accurate Leading-edge IVCT Development) continued to raise objections from the labs and clinics.

The massive spending measure provides significant added funding for veterans’ health care, while also saving billions by ending Medicaid expansion policies adopted during the pandemic. The lawmakers extend telehealth waivers for two years, continuing to support telehealth practices useful to a number of FDA programs.

The Biden administration’s Advanced Research Projects Agency for Health gains $1.5 billion funding and will reside in the National Institutes of Health. Various provisions clarify its governance, reporting requirements, leadership, and collaborations with FDA.

The legislation further aims to enhance biosecurity programs to better prepare the nation’s capacity to combat future viral epidemics and biological threats. There is increased funding for the Biomedical Advanced Research and Development Authority and to expand the Strategic National Stockpile. Added provisions support domestic production of certain antibiotics, further study on incentives for domestic production of generic drugs, and programs to enable rapid development and testing of drugs. A new White House Office of Pandemic Preparedness will oversee these efforts.

And vaccine makers and regulators will be following closely a measure setting the stage for an end to government subsidies for vaccines and medical products approved under emergency use authorization policies adopted during the COVID-19 pandemic.

A summary of the Consolidated Appropriations Act, 2023 is available at 

Jill Wechsler is Washington reporter for 

The Consolidated Appropriations Act for 2023 provides FDA with a $6.6 billion total budget.

Massive Government Spending Bill Tackles Key FDA and Research Issues

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has accepted a review of the marketing authorization application (MAA) for EQRx’s sugemalimab, an anti-programmed death-ligand 1 (PD-L1) antibody, in combination with chemotherapy for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC).

“With the acceptance of this application, we now have two investigational therapies under review with the MHRA in non-small cell lung cancer, which affects about 40,000 people annually in the UK and is a leading cause of cancer death,” said Melanie Nallicheri, president and chief executive officer of EQRx, in a press release. “This significant milestone is a step toward our goal of getting our medicines to patients and delivering on our mission of increasing access to impactful treatments."

The MAA is supported by data from the pivotal Phase III GEMSTONE-302 trial that evaluated treatment with sugemalimab in combination with chemotherapy in patients with metastatic NSCLC.

Sugemalimab was granted the Innovation Passport designation in the UK in 2021 through the Innovative Licensing and Access Pathway (ILAP) from the ILAP partner organizations, including the MHRA.

The MAA is supported by data from the pivotal Phase III GEMSTONE-302 trial that evaluated treatment with sugemalimab in combination with chemotherapy in patients with metastatic NSCLC. 



Marketing Authorization Application Accepted for Sugemalimab in Metastatic Non-small Cell Lung Cancer

US-based Discovery Life Sciences (Discovery) has launched its new Proteomic Services Division, which will serve pharmaceutical and biotech companies, government organizations, and non-profit and academic research centers. The company’s innovative offering includes both exploratory and targeted proteomics using the Seer Proteograph Product Suite, SCIEX LC-MS/MS systems, Olink Proximity Extension Assay (PEA), and Luminex xMAP platforms, according to a Dec. 14, 2022 company press release.

Discovery’s proteomic service laboratories are now integrated with the company’s short-and long-read genomic service laboratories and global commercial biorepository of hyper-annotated biospecimens. Meanwhile, as a part of its biomarker services expansion strategy, the company signed a multi-year agreement in January 2022 with Seer, a US-based life science company commercializing a disruptive new platform for proteomics, and SCIEX, a life science analytical technologies company, to form the Proteogenomics Consortium (PGC), a first-of-its-kind, according to a company press release (1), for large-scale plasma proteomic studies. The PGC combines the proprietary technologies and expertise of all three companies. The aim of the consortium is to offer unbiased, high-resolution proteogenomic services to help uncover novel biomarkers that can be mapped back to underlying genetic variations.

“We are very excited to open our doors to researchers and scientists worldwide and provide them access to Discovery’s highly-scaled, multi-omic services to advance their biomarker discovery, clinical development, and large-scale research programs,” said Michael Pisano, Discovery’s executive vice-president of Proteomics, in the company press release. “Our proteomic experts carefully designed, built, and optimized a comprehensive, platform-agnostic suite of leading-edge proteomic and proteo-genomic technologies to support all biomarker strategies, large-scale population studies, and biobank characterization projects.”

“The Proteogenomics Consortium strategically unites these highly advanced plasma proteomic technologies with our … expertise in short-and long-read genomics to add deep, unbiased proteomics data more easily to discovery, translational, and clinical studies, as well as large-scale population research programs,” said Glenn Bilawsky, CEO of Discovery, in the press release. “In addition, the PGC also enables the creation of new diagnostic tools for cancer, neurodegenerative, inflammatory, infectious diseases, and other therapeutic areas.”

1. Discovery Life Sciences, “Seer, Discovery Life Sciences, and SCIEX Announce First-Of-Its-Kind Proteogenomics Consortium for Large-Scale Studies,” Press Release, Jan. 10, 2022.

The launch of Discovery Life Sciences’ new Proteomic Services Division offers a single source for large-scale population studies, biobank characterization, and multi-omic biomarker analysis.

Discovery Life Sciences Now Offers Large-Scale Proteomic Services

AbCellera and Rallybio, a US-based clinical-stage biotechnology company, have entered into a strategic alliance to discover, develop, and commercialize novel antibody-based therapeutics targeting rare diseases. The partnership is a multi-year, multi-target collaboration that will combine AbCellera’s antibody discovery engine with Rallybio’s clinical and commercial expertise in rare diseases. Together, the companies plan to identify optimal clinical candidates and ultimately deliver therapies to patients, according to a Dec. 1, 2022 company press release.

Under the agreement, AbCellera and Rallybio will co-develop up to five rare disease therapeutic targets chosen together by both companies. The collaboration will also allow Rallybio to add product candidates to its existing pipeline. Meanwhile, AbCellera will have the option to conduct process development and clinical manufacturing activities. The first program out of the collaboration will focus on addressing the significant unmet therapeutic needs of patients with rare metabolic diseases.

“It’s clear that we need to accelerate drug development for rare diseases to address the enormous unmet medical need for these patients,” said Carl Hansen, founder and CEO of AbCellera, in the release. “Rallybio’s team has decades of experience in sourcing, identifying, and evaluating therapeutic targets. By bringing together Rallybio’s deep expertise in rare diseases with AbCellera’s integrated technology for delivering clinical leads … this partnership creates a unique advantage that we believe will deliver new and transformative medicines to patients.”

“AbCellera’s clinically validated discovery engine will strengthen our efforts in identifying novel rare disease candidates to add to our existing pipeline,” said Martin Mackay, CEO, Rallybio, in the release. “We are excited to establish this partnership and look forward to working closely with our colleagues at AbCellera as we build novel medicines together.”

AbCellera and Rallybio are teaming up to discover, develop, and commercialize novel antibody-based therapeutics for rare diseases.

AbCellera and Rallybio Partner on Novel Antibody-Based Therapeutics

Catalent announced on Dec. 14, 2022 that it is set to establish a new biologics analytical center of excellence in Durham, NC, within North Carolina’s Research Triangle, to offer analytical development and testing for biologic drug modalities, including cell and gene therapies.

Catalent plans to invest up to $40 million into the 80,000-ft2 facility. When complete, the facility will provide comprehensive solutions that include bioassays, physico-chemical testing, and full product and process characterization, as well as process validation support, stability testing, in-process manufacturing and formulation analysis, and post-packaging identification. The facility is set to be completed by mid-2023 and is anticipated to support the hiring of over 200 scientists and technicians over the next five years.

“Catalent is committed to the continuous growth and expansion of its analytical capabilities to provide extensive CMC [chemistry, manufacturing, and controls] support and solutions that are compliant with current good laboratory and manufacturing practices. By establishing significant additional capacity on the East Coast, we can offer our customers greater flexibility and expanded support services across the biologics and advanced modalities pipeline,” said Jeremie Trochu, Catalent’s division head for BioAnalytics, in a company press release. “Our Kansas City and Durham sites will together provide comprehensive services and expert solutions to companies seeking analytical support across all phases of development, ultimately reducing bottlenecks and creating an accelerated path to regulatory approval for both drug substance and drug product programs across a wide range of advanced therapies.”

Catalent is set to expand its biologics analytical services with its new facility in Durham, NC. 

BioPharm International's BP Elements, January 2023