Feliza Mirasol is the science editor for 

Feliza Mirasol

In today’s biologics/contract research organization (CRO) labs, more data than ever are being generated on protein characterization, thanks to advanced and more thorough analytical technologies. Managing these volumes of data, especially in the clinical phases of drug development, has become a real challenge for researchers.

Clinical trial data are at the heart of how biopharma companies develop new therapeutics for commercial launch, but developing a new drug and bringing it to market can take a decade or more and cost upwards of a billion dollars (1). Outsourcing clinical trial services has become a common practice to save a biopharma company on cost and time, but the practice brings up risks in data transfer as well as data management.

Laboratory issues can result in a delay of data receipt as well as poor quality of data, which can lead to rejection or rework. Data entry issues, delays in responses to data queries, errors during data transfer and merger, and discrepancies due to poor database setup can all also be the cause of delays (1).

A discussion with David Hardy, PhD, senior manager, Data Analytics and AI Enablement, Digital Science Solutions, Thermo Fisher Scientific, explores best practices for how to approach data management in today’s biopharmaceutical lab and highlights some effective strategies for distilling meaningful interpretation from these data.

 Although solutions such as laboratory information management systems (LIMS) and the electronic lab notebook (ELN) have helped to address the vast amounts of data being generated in biologics/CRO labs, what are the biggest challenges facing LIMS and ELN?

 The biggest challenge when it comes to LIMS and ELNs is ensuring that these systems fit seamlessly into laboratory processes to make sure they are used throughout an organization, at which point they can be better used to unlock deeper data-driven insights. Usability can also be a challenge of many LIMS and ELN solutions, but it is critical for company-wide, successful adoption.

Another important challenge is that, while LIMS and ELN can help ensure data quality after data capture, they can do little to rectify errors made through poor quality input data. To help improve data quality at the point of data generation, labs should seek to use automation wherever possible.

 Do automation and digitalization truly offer solutions that allow scientists to analyze these data in a meaningful way, or are there as much cons as there are pros to using such advanced technologies for the data scientist?

 The pros and cons of using automation and digitalization tools to analyze large amounts of data are the same across all applications, including biologics. For example, biologics labs still need to conduct initial validation of their tools and constantly check them, requiring close collaboration between the laboratory and data scientists. However, over time, the pros of advanced digitalization and automation tools—greater accuracy, reproducibility, efficiency, and deeper insight—vastly outweigh any initial cons.

Importantly, even with advanced technologies, scientists face the hurdle of understanding their data and which data fields to use. Then, they need to be clear on which model best suits the problem they’re trying to solve. This isn’t always easy but analytics solutions are striving to make this simpler.

 How has the user (i.e., the scientists) experience been affected or changed by the amount and quality of data being generated and the ability to manage that data?

 By their nature, scientists are data savvy. However, with the sheer amount of data that labs generate, as well as the need to manage these data with advanced technologies, scientists have had to become more tech savvy. For example, most scientists have the knowledge and skills to check and analyze their data using languages such as R, Python, and tools such as KNIME [Konstanz Information Miner]. Given the growing importance of these skills, they are now widely taught to undergraduate students.

Scientists have also embraced ‘big data,’ adopting new technologies to such an extent that big data isn’t the obstacle it once was. Given the increasing importance of technology in handling and processing such data, scientists now commonly work alongside their data science, IT [information technology], and TechOps [technical operations] colleagues to find the optimum and most cost-effective solution, which was less common in the past.

Beyond data capture, storage, and analysis, labs increasingly need to be able to use their data to their full potential. Accordingly, we’ve seen scientists increasingly focus on the FAIR (findable, accessible, interoperable, and reusable) data principles. Data [are] only truly useful if [they meet] these requirements.

 What would you say are some key best practice habits or techniques that scientists can employ to managing these data?

 Scientists can—and should—do several things to maximize their ability to manage these data. First, they should embrace automation, as it’s a scientist’s best friend. With more automation, scientists get free time to focus on more important, value-adding activities.

Scientists should also keep in mind that managing all of these data is a team sport. Data Science, IT, and TechOps teams are there to help, so scientists should leverage their expertise and support to maximize their chances of overcoming data challenges.

Finally, scientists should keep up to date on the latest technologies for managing and analyzing data—the field is advancing very rapidly, and taking your eye off the ball, even briefly, can lead to missed opportunities.

 What are some effective strategies that scientists can use to ensure that they are processing quality lab data and not just noise (are there such strategies)?

 As the saying goes, ‘garbage in, garbage out.’ That is to say that the root of good quality data is good input—good experiment design followed by good execution. Scientists can achieve these in several ways.

For example, they can adopt electronic tools such as laboratory execution systems (LES), which help by ensuring scientists follow methods and procedures correctly. LES and LIMS can also flag anomalous result values that fall outside a given specification range, helping to ensure data quality.

Scientists should also look to adopt artificial intelligence (AI) technologies, as they can greatly help in improving data quality. But this doesn’t have to be an overwhelming task. It can help to start with a small project and build from there. For example, a lab might start by using an AI-based approach to identify systematic errors, before gradually expanding its remit and functionality. It’s important to engage the data science team early and draw on their experience as you embark on this new and exciting journey.

1. Johnson, J.; Kanagali, V.; Prabu, D. Third Party Laboratory Data Management: Perspective with Respect to Clinical Data Management. 

 (1), 41–44. DOI: 10.4103/2229-3485.124573

Articles

Advanced analytical tools generate more data in today’s labs than ever before.

Dealing with Data: How to Keep It Manageable

On Aug. 28, 2023, US-based Cellares, an integrated development and manufacturing organization (IDMO), announced that Bristol Myers Squibb has joined its Technology Adoption Partnership (TAP) program, a program that offers cell therapy developers opportunity to adopt Cellares’ automated manufacturing technology platform, the Cell Shuttle. Under the agreement, Bristol Myers Squibb will submit a proof-of-concept transfer process for the manufacture of one of its chimeric antigen T cell (CAR-T) cell therapies using the Cell Shuttle.

According to a company press release, Bristol Myers Squibb will use the program to evaluate Cellares’ automated manufacturing process and produce comparability data to confirm that the Cell Shuttle is a viable, cost-efficient, and scalable manufacturing solution for cell therapies. Through its TAP program, Cellares is working with cell therapy developers to implement its manufacturing platform as a clinical and commercial-stage good manufacturing practice (GMP) manufacturing solution at its IDMO smart factories.

The company’s technology platform can support both autologous and allogeneic cell therapy processes as well as approximately 90% of cell therapy modalities. According to the company press release, manual processes can be automated and tech-transferred onto Cellares’ automated Cell Shuttle platform in six months’ time using the TAP program. Under TAP, participating cell therapy developers can tech-transfer their cell therapy processes onto a Cell Shuttle at any stage, such as during pre-clinical development, or in the clinic, or after regulatory approval. Automation, standardization, and software-defined manufacturing combine to make any follow-up tech transfer thereafter instantaneous to any other Cell Shuttle in any other IDMO smart factory in any global location, according to the press release.

“We’re pleased to welcome Bristol Myers Squibb to the TAP program, and we look forward to demonstrating the ease and efficacy of transferring one of [the company’s] cell therapy process[es] onto the Cell Shuttle in the months to come,” said Fabian Gerlinghaus, CEO, Cellares, in the press release. “By combining integrated automation with a high-throughput platform, the Cell Shuttle offers unrivaled scalability for the cell therapy industry, while improving quality and lowering COGS [cost of goods sold].”

The launch of the IDMO and smart factories

The partnership with Bristol Myers Squibb follows on the heels of Cellares’ initial launch as an IDMO, the first of its kind dedicated to clinical and industrial-scale cell therapy manufacturing, according to an Aug. 23, 2023 company press release. At the time of its launch, Cellares had raised $255 million in Series C funding, which was led by US-based investment firm Koch Disruptive Technologies and in which Bristol Myers Squibb participated, along with others.

With this funding, Cellares launched a commercial-scale IDMO smart factory in Bridgewater, NJ, the first of its kind, according to the company press release. The 118,000-ft2 smart factory is designed to integrate advanced robotics, purpose-built technology, and interconnected software and will be capable of producing 40,000 cell therapy batches per year. The Bridgewater site will be GMP-ready in the second half of 2024. Under the integrated technologies, IDMO smart factories can produce 10 times more cell therapy batches per year than traditional contract development and manufacturing facilities and with the same footprint and workforce, according to the release.

Cellares currently operates two smart factories in the United States and is planning a third. Its first smart factory, located in San Francisco, Calif., is currently being used for preclinical process development and for the tech transfer of manual processes onto the company’s Cell Shuttle platform for existing partners. The San Francisco facility will be GMP-ready in early 2024, according to the company press release. Cellares intends to deploy its smart factories around the world to serve global patient demand for cell therapies and will break ground on the first IDMO smart factory in Europe in 2024.

“The creation of the first IDMO marks the beginning of a new era, in which cell therapies will finally be able to reach those in need,” said Gerlinghaus in the press release. “We’ve developed integrated technologies for the entire drug development and manufacturing life cycle. Now we’re leveraging these technologies to offer global manufacturing services for the living drugs of the 21st century. Our partners are some of the best academics, biotechs, and large pharma companies in the world. We’re enabling them to meet total patient demand, improve consistency and quality, lower manufacturing costs, and accelerate expansion to new markets.”

Bristol Myers Squibb has joined Cellares’ Technology Adoption Partnership program just as Cellares launches operations as an integrated development and manufacturing organization.

Bristol Myers Squibb Joins Cellares Program Focused on Automated Cell Therapy Manufacturing as Cellares is Launched as First IDMO

Rentschler Biopharma announced a collaboration on Aug. 23, 2023 with Cell and Gene Therapy Catapult (CGT Catapult), a UK-based independent innovation and technology organization specializing in cell and gene therapies, and Refeyn, a UK-based provider of mass photometry instruments and technologies, under which the three organization will develop and apply innovative process analytical technologies (PAT) to improve the manufacturing process for adeno-associated viruses (AAVs) in gene therapy production.

Under this two-year collaboration, the partners aim to develop a digitized and automated AAV gene therapy manufacturing platform. Through a combination of expertise in manufacturing, process analytics, and PAT, the collaborators will develop automated monitoring and control that will then be applied to Rentschler Biopharma’s existing AAV manufacturing process.

Because current analytical methods related to AAV production mainly rely on manual sampling, the production of AAVs has been difficult and time consuming. However, over 65% of gene therapies in development currently rely on AAV vectors.

To address the AAV manufacturing challenges, the teams under this collaboration will carry out high throughput and automated sampling and analysis of AAV material throughout the production process. The data collected from this analysis will be used to create digital twins, which are digital models of the manufacturing process that can be used to further refine and improve the efficiency of the process.

Thus, using the digital twins, the teams can carry out initial tests on any changes to the manufacturing process in a digital environment. Troubleshooting in this fashion would reduce the number of expensive and time-consuming physical tests that otherwise would be needed to be carried out in the laboratory, according to a company press release.

The collaborators will assess any improvements in productivity and AAV yield using automated analytical technologies, which will include Refeyn’s technology to assess the proportion of full AAV capsids produced. Assessing the proportion of full AAV capsids produced is a key measurement for the industry; the quantity of full AAV capsids indicates process efficiency but may also impact clinical efficacy, according to the press release. Refeyn will additionally use this project to test a new current good manufacturing practice-compliant version of its mass photometer.

“With this collaborative project … we seek to unleash the potential of faster viral vector development with multi-parameter driven optimization,” said Christian Schetter, chief scientific officer, Rentschler Biopharma, in the press release. “This promises to translate to higher outputs, robustness, and better process control; ultimately lowering the risk associated with the transition from early to late-stage manufacturing for the benefit of our clients and their patients.”

“The outputs will help us understand the future needs of viral vector manufacturing environments, informing product development to better satisfy these needs,” said Matthias Langhorst, chief product officer, Refeyn, in the release.

The project is being funded through a grant from Innovate UK.

Rentschler Biopharma, CGT Catapult, and Refeyn aim to use automated and digital technologies to improve AAV manufacturing for gene therapies.

Three-Way Collaboration Between Rentschler Biopharma, CGT Catapult, and Refeyn Aims to Improve PAT for Gene Therapy Manufacturing

On Aug. 28, 2023, Danaher, an innovator of science and technologies, announced that it has entered into a definitive agreement to acquire UK-based Abcam, a supplier of protein consumables, for approximately $5.7 billion ($24.00 per share). Under the agreement, Abcam will operate as a standalone operating company and brand within the life sciences segment of Danaher.

The transaction, which is expected to close in mid-2024, is in line with Danaher's strategy to facilitate the mapping of complex diseases and accelerate the drug discovery process. According to a company press release, Danaher expects to fund the acquisition with cash on hand and proceeds from the issuance of commercial paper.

Headquartered in Cambridge, UK, Abcam supplies validated antibodies, reagents, biomarkers, and assays. The company’s offerings help researchers to address targets in biological pathways that are considered critical for advancing drug discovery as well as life sciences research and diagnostics.

"We couldn't be more excited to have Abcam join Danaher. Abcam's long track record of innovation, … product quality, and breadth of antibody portfolio positions them as a key partner for the scientific community,” said Rainer M. Blair, president and CEO, Danaher, in the company press release. “We look forward to welcoming Abcam's innovative and talented team to Danaher as we continue to help our customers solve some of the world's biggest healthcare challenges."

"Our strategy has transformed Abcam to become a scale innovator and important catalyst in the global life science community. Danaher shares our passion to help life science researchers achieve their mission faster, and [its] operating company model allows us to continue to pursue our strategy, while harnessing the power of the Danaher Business System to ensure we remain the partner of choice for our customers," said Alan Hirzel, CEO, Abcam, in the release.

Danaher intends to acquire Abcam, a provider of life sciences assays and reagents, for $5.7 billion.

Danaher to Acquire Abcam in $5.7 Billion Deal

On Aug. 18, 2023, Regeneron Pharmaceuticals announced that FDA has approved Veopoz (pozelimab-bbfg), a monoclonal antibody, for treating adult and pediatric patients one year and older with CHAPLE disease, or CD55-deficient protein-losing enteropathy. The company also announced that FDA has approved Eylea HD (aflibercept) Injection 8 mg, a high-dose version of Eylea, for treating wet age-related macular degeneration (wAMD), diabetic macular edema (DME), and diabetic retinopathy.

According to a company press release, the pozelimab approval marks the first and only treatment indicated specifically for CHAPLE. This approval also signals that pre-approval inspection issues related to the aflibercept 8 mg biologics license application (BLA) have been addressed and that FDA action on the aflibercept 8 mg BLA is expected in the next few weeks.

CHAPLE is a rare, hereditary life-threatening immune disease that is driven by an overactivation of the complement system. Normally, the complement system in healthy individuals is a mechanism for destroying microbes. For those living with CHAPLE, however, individuals are unable to regulate complement activity because of mutations in their CD55 gene, and without proper CD55 regulation, the complement system may attack normal cells. This can cause damage to blood and lymph vessels along the upper digestive tract and lead to loss of circulating proteins. According to the press release, fewer than 10 patients have been identified in the United States who have the disease.

“Most patients with CHAPLE disease are children who face severely debilitating symptoms and often life-threatening complications that begin in infancy,” said Michael Lenardo, chief, Molecular Development of the Immune System Section and co-director, Clinical Genomics Program, National Institute of Allergy and Infectious Disease, National Institutes of Health, in the company press release. “As an investigator in this pivotal trial and one of the discoverers of this disease, I saw first-hand the transformational clinical improvement that pozelimab achieves in those suffering from CHAPLE. The approval of pozelimab is a milestone to celebrate, providing a new medicine that can help these long-suffering patients.”

“Beyond CHAPLE, we believe [pozelimab] has promise in a variety of complement-mediated diseases and are driving forward several clinical programs to explore its broader potential,” said George D. Yancopoulos, board co-chair, president, and chief scientific officer, Regeneron, in the release.

Meanwhile, the approval of Eylea HD Injection 8 mg was based on the 48-week results of two double-masked, active-controlled pivotal trials (PULSAR in wAMD and PHOTON in DME) which evaluated Eylea HD compared to Eylea Injection 2 mg. Both trials met their primary endpoint. Eylea HD demonstrated non-inferior and clinically equivalent vision gains at 48 weeks (with both 12- and 16-week dosing regimens following three initial monthly doses), compared to an Eylea 8-week dosing regimen after initial monthly doses. According to a company press release, the vast majority of patients randomized at baseline to Eylea HD 12- or 16-week dosing regimens (following the three initial monthly doses) were able to maintain these dosing intervals throughout the 48 weeks.

“The FDA approval of Eylea HD is an important advancement in retinal care,” said Peter Kaiser, Chaney Family endowed chair in Ophthalmology Research at the Cole Eye Institute and professor of Ophthalmology at Cleveland Clinic Lerner College of Medicine, in the release. “With Eylea HD, patients with wet age-related macular degeneration or diabetic retinal disease can now receive less frequent injections after their initial monthly doses and still experience the similar visual gains, anatomic improvements, and safety profile of Eylea.”

FDA has approved a new mAb therapy from Regeneron Pharmaceuticals as well as a higher dose version of Eylea, the company’s eye disease therapeutic.

Regeneron Gets FDA Approvals on New Biologic and New High Dose for Eye Disease Therapy

On Aug. 21, 2023, Gilead Sciences announced that FDA has placed a partial clinical hold on the company initiating new patients into US studies for magrolimab, an investigational anti-CD47 immunotherapy, to treat acute myeloid leukemia (AML). FDA’s decision follows a previous announcement in which a Phase III clinical study was discontinued that was studying magrolimab in higher-risk myelodysplastic syndromes (1).

According to a Gilead company press release, screening and enrollment of new study participants under US investigational new drug application (IND) 147229 and a US expanded access program will be paused, effective immediately. However, patients who are already enrolled in AML clinical studies may continue to be treated and monitored, according to study protocol. Meanwhile, studies of magrolimab in solid tumors may continue and are not impactd by this FDA action.

Global regulatory authorities and clinical trial investigators involved in the studies have been informed of FDA’s decision. Gilead is working with regulatory authorities to determine the next steps needed to release the partial clinical hold.

Magrolimab is an investigational molecule that has not been approved anywhere globally, and Its safety and efficacy have not yet been established. In addition to AML, magrolimab is being developed as a potential treatment for myeloid malignancies, lymphoma, myeloma, head and neck cancer, colorectal cancer, lung cancer, and breast cancer.

1. Gilead Sciences, Gilead To Discontinue Phase 3 ENHANCE Study of Magrolimab Plus Azacitidine in Higher-Risk MDS. Press Release, July 21, 2023.

FDA has halted enrollment in clinical studies for Gilead Sciences’ magrolimab, a biologic treatment in development for acute myeloid leukemia.