Felicity Thomas is Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

Felicity Thomas

Close-up of a microscope lens examining microarray slides, a crucial tool in genomic research and medical diagnostics | Image Credit: © Varunee - Stock.Adobe.com

It is well-known that developing a drug from the discovery through to commercialization is a costly endeavor, with market analysis showing that the average R&D cost to develop an asset for 2022–2023 was $2.3 billion (1). However, many drugs do not make it through to commercialization, in fact it has been reported that clinical attrition rates for drugs that have reached Phase I trials is as high as 90% of drug candidates (2).

As a result of the high costs and level of risk inherent with drug development, it is imperative that companies efficiently determine the safety and efficacy of their candidates, to minimize any potential failure. “Bioanalytical testing is essential in drug development because it ensures the safety, efficacy, and quality of pharmaceutical compounds through quantitative analysis of drugs and their metabolites in various biological matrices such as plasma, urine, blood tissue, [and so on],” asserts Sujata (Suzzy) Bhavekar, study director at SGS North America. “Early identification of side effects through rigorous testing can reduce development costs by up to 20% (3). Drugs with robust bioanalytical data are 50% more likely to gain regulatory approval (4).”

“Bioanalytical testing covers a range of techniques and technologies used to quantify drugs and their metabolites, or biomarkers, in biological media,” adds Iain Love, director, Chromatographic Bioanalysis & Discovery Sciences, Department of Chromatographic Bioanalysis, Charles River. “The concentration data generated through bioanalytical testing are important as they inform researchers on how long a drug stays in the body and the beneficial effects or otherwise while it’s in there. Knowing the concentration of drug candidates and understanding the levels at which the drug has positive or negative effects on the body is critical to drug development.”

Vital data on drug absorption, distribution, metabolism, and excretion can be gained through bioanalytical studies, which helps developers to determine dosing regimens, agrees Bhavekar. “Poor pharmacokinetics contribute to 30% of drug failures, highlighting the importance of accurate testing (5),” she says.

Additionally, bioanalytical studies help with biomarker discovery, which improves the success rate of targeted therapies by 25% and supports personalized medicines (6), Bhavekar continues. Furthermore, suitable bioanalytical testing helps ensure compliance with regulatory standards, including good laboratory practice (GLP) and good clinical practice (GCP). “Approximately 85% of drug applications meet approval criteria with solid bioanalytical data (7),” Bhavekar says.

“Regulatory considerations are extremely vital in bioanalytical studies to ensure compliance with international standards and facilitate successful drug approval,” continues Bhavekar. “Adhering to GLPs and GCPs is essential to ensure data accuracy, reliability, and reproducibility.”

“Bioanalytical testing is carried out according to strict inter(national) guidelines and quality management systems,” agrees Love. “Monitoring authorities translate globally recognized quality management systems into national regulations.”

At the national level, there are guidelines such as FDA’s guidance documents on bioanalytical method validation and immunogenicity (7,8) and the European Medicines Agency’s guidance on bioanalytical method validation (9), Bhakevar adds. “Compliance with 21 CFR [Code of Federal Regulations] Part 11 (10) is crucial for maintaining the credibility of electronic records and ensuring data integrity,” she says.

“In addition to these national regulations, bioanalytical studies are also carried out following the International Council for Harmonisation (ICH) M10 guideline,” confirms Love. In fact, EMA’s guidance on bioanalytical testing has been superseded by the ICH guidance (11), since its publication in 2022.

“The ICH M10 guideline provides a harmonized approach across various regions including the US [United States], EU [European Union], Japan, and other member countries [and] provides a robust framework for validating methods, focusing on precision, accuracy, selectivity, sensitivity, and reproducibility, thus enhancing global consistency in bioanalytical testing,” Bhakevar specifies. “These regulatory frameworks, including ICH M10 and FDA guidelines, form the backbone of robust bioanalytical testing, driving drug development toward clinical and commercial success.”

“Outsourcing partners are an increasingly important piece of the drug development puzzle,” notes Love. “Partnership with a bioanalytical provider can bring about several tangible advantages that can help get drugs to the patients who need them in the shortest time possible. This could be from simple access to appropriate analytical platforms to receiving advice on planning the development program.”

In terms of regulatory compliance, the right partnership with a contract research organization that complies with global regulatory standards can ensure that the bioanalytical data generated meets the relevant requirements, Bhakavar explains. “Comprehensive services [provided by a partner company], including method development, validation, and routine analysis, allow sponsor companies to focus on core R&D activities while relying on their outsourcing partner for specialized testing,” she says.

“Outsourcing partners are also likely to be able to apply experience gathered from across a broad portfolio of modalities and development scenarios that can inform program decision-making,” confirms Love. “More than ever, bioanalytical science is involved in shaping programs, so careful selection of an expert outsourcing partner is an activity that can bring about the significant benefits involved with an accelerated drug development program.”

There are also benefits in terms of the flexibility and scalability of operations that a partner company can provide for a sponsor’s needs, Bhavekar remarks. “Outsourcing provides flexibility in scaling bioanalytical operations according to project needs, from preclinical to late-stage clinical trials. This scalability helps manage resources efficiently and reduces the burden on in-house teams,” she says. “[Additionally], with large-scale facilities and automated processes, outsourcing partners can handle high volumes of samples, ensuring rapid data delivery and accelerating the drug development timeline.”

“[Furthermore], outsourcing partners invest in cutting-edge technologies and platforms, such as mass spectrometry and immunoassays, to deliver precise and reliable data, which may not be feasible for smaller companies to implement internally,” specifies Bhavekar. “Overall, outsourcing bioanalytical testing to a reputable partner can enhance the efficiency and quality of the drug development process, enabling sponsor companies to achieve their project goals more effectively.”

“There has never been a more vibrant time to be involved in bioanalytical testing. It’s sometimes a challenge to keep up with the innovation both from within the drug development industry and from supporting partners,” notes Love. “There have been, and continue to be, some hugely innovative therapies discovered and developed by the pharma and biotech sectors. At the same time, instrument and software manufacturers continue to push boundaries with what can be done to generate extremely powerful data in support of drug development.”

An area of great interest for Love is that of patient centric sampling (PSC), which is “the description given to a number of techniques and approaches that affords patients choice: choice on how a biosample is taken but also the choice of whether to provide biosamples in a clinical setting or remote from a clinical setting,” he says. “This enablement of decentralized trials is potentially the biggest and most impactful paradigm change in the clinical space for a long time.”

For Bhavekar, the many advancements that have been seen in the field of bioanalytical testing have helped to greatly improve the analysis of both small and large molecules in drug development. For example, she highlights the hybrid approach of combining ligand-binding assays with liquid chromatography coupled with tandem mass spectroscopy as a way of improving sensitivity and specificity of bioanalytical studies for both small and large molecules.

Platform approaches represent another advancement in the field, Bhavekar continues. “Enzyme-linked immunosorbent assay, plasmon resonance immunoassay, hybridization assay, immuno-PCR [polymerase chain reaction] assay, and the Meso Scale Discovery platform are widely utilized methodologies,” she says. “These platforms are highly specific and sufficiently sensitive, enabling the generation of controlled and customized data that meets regulatory compliance standards.”

Other advancements include chromatographic-based techniques for greater analysis of samples, circular dichroism and differential scanning colorimetry for the assessment of stability and structural changes in large molecules, electrophoresis to help with the separation of proteins and large-molecule characterization, and multiplex immunoassays to gain insights into complex biological samples, Bhavekar notes.

“The bioanalytical field is continuously evolving, with ongoing research into novel biomarkers, advanced detection methods, and personalized medicine approaches. Staying at the forefront of these innovations is crucial for maintaining a competitive edge in the industry,” concludes Bhavekar. “By focusing on [more than just the core] aspects, sponsor companies can leverage bioanalytical testing not just as a regulatory requirement but as a strategic tool for advancing drug development and achieving market success.”

1. May, E.; Taylor, K.; Gupta, L.; Miranda, W. 

Unleash AI’s Potential: Measuring the Return from Pharmaceutical Innovation—14th Edition

. Annual Report, Deloitte, April 2024.
2. Sun, D.; Gao, W.; Hu, H.; Zhou, S. Why 90% of Clinical Drug Development Fails and How to Improve it? 

 12 (7) 3049–3062.
3. Smith, J. and Doe, A. The Impact of Early-Phase Clinical Testing on Drug Development Costs. 

Pharmaceutical Development and Technology

 24(3), 225-233.
4. FDA. Drug Approval Statistics. 2022 Retrieved from https://www.fda.gov/drugs/drug-approvals-and-databases.
5. Anderson, J. and Smith, R. Impact of Pharmacokinetics on Drug Development. 

Journal of Pharmacokinetics and Pharmacodynamics

, 48(2), 123-130.
6. Johnson, R. and Lee, K. Biomarker Discovery and Its Role in Targeted Therapy. 

. Guidance for Industry, May 2018.
8. FDA. 

Immunogenicity Testing of Therapeutic Protein Products — Developing and Validating Assays for Anti-Drug Antibody Detection

. Guidance for Industry, January 2019.
9. EMA. EMEA/CHMP/EWP/192217/2009 Rev. 1 Corr. 2** 

Guideline on Bioanalytical Method Validation

 Title 21, 11 (Government Printing Office, Washington, DC) 241–246.
11. ICH. M10 

Bioanalytical Method Validation and Study Sample Analysis

Felicity Thomas is the Associate Editorial Director for Pharmaceutical Technology Group.


Vol. 48, No. 12
December 2024
Pages: 30–32

When referring to this article, please cite it as Thomas, F. 
Leveraging Advancements in Bioanalytical Testing. 

Articles

As the field of bioanalytical testing evolves, it is important for drug developers to stay at the forefront of the advancements to ensure they remain competitive.

Leveraging Advancements in Bioanalytical Testing

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 will be moving into its 36th year as a published industry resource. Over the course of the past 35 years, the magazine has undergone a variety of changes, such as updated page designs and the inevitable changes in staff, but our ethos of providing the highest quality, most pertinent content for our readership has always remained the same.

 was published back in 1989, which was the same year that the first guidelines on good manufacturing practices for the European bio/pharma industry were published (1). Since that time, the industry, and the European region as a whole, has undergone a huge amount of change—from novel therapies to new regulations and, most recently, a drive towards digitalization and the adoption of more automated approaches.

 has had the immense responsibility and pleasure to provide a comprehensive overview of the relevant trends that impact our readers daily lives. And an important aspect of being able to perform this task successfully is considering our readership’s habits over time.

Over the course of the past couple of years, we have been discussing the future of our publication and how we can best serve you, our readers, with a variety of industry stakeholders. Through these discussions, we believe that now is the right time for us to transition from print media and become a fully digital publication in 2025. So, in the new year, 

will be distributed as a digital publication that will not only include our technical articles and expert-authored columns but will also provide a host of new interactive elements and content for our readers.

I am thrilled to be able to steer the ship towards the digital world and hope you will find our new interactive format a useful experience. We invite you to share your thoughts with us on our new look and welcome your feedback on where we can improve our offerings further.

Our first digital issue will be published in February 2025, until then, have a great festive break and here’s to a prosperous 2025 and beyond!

1. EC. 50 Years EU Pharmaceutical Regulation Milestones. Public Health Infographic, 


Vol. 36, No. 10
November/December 2024
Page: 6

When referring to this article, please cite it as Thomas, F. New Year, New PTE. 

Aligned with our audience’s preferences, PTE will be a fully digital publication from 2025 onwards.

New Year, New PTE

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Swiss biotechnology company, Roche, has entered into a definitive agreement to acquire clinical-stage biopharmaceutical company, Poseida Therapeutics. The merger agreement was announced by Roche in a Nov. 26, 2024 company press release (1).

Under the terms of the merger, Roche will gain access to Poseida’s good manufacturing practice (GMP) manufacturing capabilities and its R&D assets, in addition to the programs and pipeline products that the companies are currently collaborating on. Assets that will be incorporated fully into the Roche Group on completion of the acquisition include allogeneic chimeric antigen receptor (CAR) T-cell therapeutic programs aimed at B-cell malignancies, hematologic malignancies, and solid tumors, among other things.

“This exciting acquisition will allow us to drive further progress in allogeneic cell therapy while leveraging the successful existing partnership with Poseida,” said Levi Garraway, head of Product Development and chief medical officer at Roche, in the press release (1). “We are very encouraged by the early clinical data, and this acquisition builds on our joint progress to catalyze the development of potentially first and best-in-class cell therapies in oncology, immunology, and neurology.”

The merger agreement between the two companies builds upon their existing strategic relationship that was initially formed in 2022 and was aimed at the development of off-the-shelf CAR-T cell therapies to address the unmet medical needs of patients with hematologic malignancies (2). Moving forward, Poseida therapeutics, Roche, and Genetech—a member of the Roche Group—will focus on delivering the next generation of off-the-shelf CAR-T cell therapies with higher potency and favorable safety at scale to be able to reach a broader patient population.

“Our interest in cell therapy is directly tied to our commitment to discovering and developing pioneering medicines with substantial patient benefit,” added Aviv Regev, head of Genentech Research & Early Development. “We are excited to bring together cutting-edge scientific approaches and expertise to tap into the full transformative potential of cell therapy.”

A tender offer will be provided by Roche to acquire all outstanding shares of Poseida Therapeutics’ common stock at a value of US $9 per share, which represents a total equity value of approximately US $1 billion. Both boards of Roche and Poseida Therapeutics have already unanimously approved the merger agreement. The transaction is expected to close during the first quarter of 2025 and is subject to the relevant closing conditions.

1. Roche. Roche Enters into a Definitive Agreement to Acquire Poseida Therapeutics, Including Cell Therapy Candidates and Related Platform Technologies. Press Release, Nov. 26, 2024.
2. Poseida Therapeutics. Poseida Therapeutics Announces Strategic Global Collaboration with Roche Focused on Allogeneic CAR-T Cell Therapies for Hematologic Malignancies. Press Release, Aug. 3, 2022.

The acquisition will provide Roche with access to Poseida’s GMP manufacturing capabilities and R&D portfolio assets, including cell therapy candidates.

Roche Enters Definitive Merger Agreement to Acquire Poseida Therapeutics

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German contract development and manufacturing organization (CDMO), Adragos Pharma, has announced its acquisition of Swiss aseptic fill/finish manufacturing company, Baccinex, in a Nov. 25, 2024 press release (1). Through the acquisition, Adragos Pharma will enhance its sterile manufacturing capabilities and expand its global network.

Baccinex has more than 20 years of experience in aseptic fill/finish services for liquid and lyophilized vials and is based in Courroux, Jura, in Switzerland. The company’s Jura facility is both European Union (EU)-good manufacturing practice (GMP) and US FDA-certified and specializes in clinical trial supplies and small-to-medium scale commercial production.

Under the acquisition agreement, Dr. Ursula Bausch, who founded Baccinex, will continue her position as CEO and she will also remain a shareholder in the company. “Joining Adragos Pharma marks a new chapter for Baccinex. Our shared commitment to quality, innovation, and customer-centric solutions creates an exciting synergy that will enable us to deliver even greater value to our clients worldwide,” Bausch said in the press release (1).

Additionally, the acquisition of Baccinex aligns with Adragos Pharma’s global expansion strategy. “The acquisition of Baccinex represents a significant milestone for Adragos. Baccinex’s proven expertise in sterile liquids and lyophilization, combined with its operational excellence, enhances our ability to provide integrated solutions from development through to commercial supply. This addition strengthens our position as a global partner of choice for high-quality pharmaceutical manufacturing,” added Dr. Andreas Raabe, founder and CEO of Adragos Pharma, in the press release (1).

Adragos Pharma has been making strides to further its global footprint with various acquisitions and, in addition to the most recent Swiss addition, has manufacturing sites located in Germany, France, Greece, Norway, and Japan.

On Nov. 7, 2024, the company announced the launch of a cutting-edge ampoule filling line at its Livron facility in France, enhancing its production capacity to over 160 million ampoules per year (2). “We recognized not only a regulatory demand in Annex 1 but also an urgent need for greater capacity, particularly for larger-volume ampoules. That’s why we installed this fourth line, allowing us to offer a capacity of over 160 million ampoules, including options up to 20 mL, tailored to serve our clients’ evolving requirements,” explained Marco Gorgas, CCO of Adragos Pharma in a press release (2).

In April 2024, Adragos Pharma also highlighted its actions to reinvest in the solid dosage market through their plans to enhance the manufacturing capacity of its Kawagoe plant in Japan to meet the anticipated demand of 2 billion tablets in the future (3). “Our business has progressed seamlessly, surpassing our initial goals. Moving into the second year and beyond, we will further enhance the manufacturing capacity of the Kawagoe plant, primarily focusing on solid formulations, to meet (growing) demands,” stated Keizo Yanagisawa, president and representative director of Adragos Pharma, in a press release (3).

1. Adragos Pharma. Adragos Pharma Acquires Baccinex—A Leading Swiss Sterile Fill-Finish Expert. Press Release, Nov. 25, 2024.Swiss Sterile Fill-Finish Expert. Press Release, Nov. 25, 2024.
2. Adragos Pharma. Project Future: We Launched Our New Production Line in Our Livron Facility! Press Release, Nov. 7, 2024.
3. Adragos Pharma. Our Strategic Expansion in Japan: Reinforcing Production to 2 Billion Tablets and Aiming to be the “Most Trusted CDMO”. Press Release, April 8, 2024.

Through this acquisition, the German CDMO expands its global network and adds aseptic fill/finish and lyophilization expertise to its sterile manufacturing capabilities.

Adragos Pharma Strengthens Sterile Manufacturing Capabilities with Baccinex Acquisition

Ask the Expert Episode 6: Non-Animal Derived Reagents

In this episode of the Ask the Expert video series, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, and Siegfried Schmitt, vice president, Technical at Parexel, discuss the new chapter, Chapter <86> Bacterial Endotoxins Test Using Recombinant Reagents, published by the 

United States Pharmacopeia–National Formulary 

November 2024. The chapter permits the use of non-animal-derived reagents for endotoxin testing and is part of USP’s commitment to expanding the use of animal-free methods and materials (1).

“Twenty years ago, the predominant test procedure for determining endotoxin level, or pyrogen level, as we called it, was the rabbit test. And we used to actually inject rabbits, which was a very subjective because you'd measure their temperature,” says Schniepp. And then we evolved to using the limulus amoebocyte lysate or LAL test, and there was the chromogenic [test] but they were all predicated off the horseshoe crab. So now we're moving forward to reagents for this test, which is critical to the release of sterile injectables that does not involve animals. So absolutely, we should consider this.”

“I think it is also worthwhile mentioning that what is happening in the US is mirrored in other jurisdictions, for example, when you look at the European Medicines Agency [EMA], they support the use of animal free cell culture reagents as part of its efforts to reduce animal use in medicine testing,” adds Schmitt. “We don't want to use rabbits. We don't want to use horseshoe crabs, and it's EMA’s innovation task force that encourages that use of alternative methods to animal models, and that, what they say is, will improve the scientific quality and also, of course, animal welfare.”

Click the video above to watch Sue and Siegfried answer the following question:

"USP just published a new chapter on the use of non-animal derived reagents. We are not currently using non-animal derived reagents. Is this something we should consider changing?"

Chapter for Endotoxin Testing Using Non-Animal Derived Reagents Published for Early Adoption

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to PTProjects@mmhgroup.com, and it may appear in a future episode or print column.

Videos

In this episode of the Ask the Expert video series, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, and Siegfried Schmitt, vice president, Technical at Parexel, discuss the new chapter, Chapter <86> Bacterial Endotoxins Test Using Recombinant Reagents

Non-Animal-Derived Reagents for Endotoxin Testing

Eisai Europe and Biogen have received a positive opinion from the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) for the use of their amyloid-beta (Ab) monoclonal antibody (mAb) lecanemab in treating adult patients with a clinical diagnosis of mild cognitive impairment and mild dementia due to Alzheimer’s disease (early AD). The positive opinion, announced by Eisai in a Nov. 15. 2024 press release, was primarily based on data from a global Phase III clinical trial (1).

Patients in the European Union (EU), who will be eligible for treatment once the European Commission has made its final decision on the treatment, would be those who are apolipoprotein E ε4 (ApoE ε4) non-carriers or heterozygotes with confirmed amyloid pathology. ApoE is a protein that is involved in the metabolism of fats in humans and has been identified as the strongest genetic risk factor for sporadic AD and an important biomarker to determine disease susceptibility (2).

“[The] positive CHMP opinion brings us one step closer to being able to offer a potential treatment option which targets an underlying cause of AD to eligible patients in the EU for the first time,” said Gary Hendler, regional chairman and CEO, Eisai EMEA, senior vice-president and global corporate officer, Eisai Co. Ltd, Tokyo, in the press release (1). “AD is a progressive neurodegenerative disease that poses significant challenges to human health and wider society—the loss of someone’s memory and independence can have a significant impact on not only those living with the disease, but also their family and friends. Eisai is committed to making a meaningful difference to all those affected by AD, and we are pleased that our ongoing work with the CHMP is helping to make this available to eligible patients in the EU.”

CHMP’s opinion has been sent to the European Commission for its final review, with a decision on the marketing authorization application expected within 67 days of receipt of the opinion. Lecanemab is already approved in the United States, China, Japan, South Korea, Hong Kong, Israel, the United Arab Emirates, and Great Britain, and is under review in 17 countries.

“The positive CHMP opinion marks a significant step and recognizes the potential of this medicine to make a difference to eligible individuals and their families impacted by this disease. We look forward to the EC’s decision and are pleased to be one step closer to offering this medicine in the EU,” added Wolfram Schmidt, president, head of Europe, Biogen, in the press release (1). “As a company, we are dedicated to furthering Alzheimer’s disease research and treatment, aiming to help address the unmet needs in this devastating condition.”

Lecanemab (brand name Leqembi) is a humanized immunoglobulin gamma 1 (IgG1) mAb that selectively binds to soluble Ab aggregates (protofibrils) and insoluble Ab fibril aggregates. According to research, the reduction of Ab protofibrils has been highlighted as potentially useful in reducing the progression of AD (3).

1. Eisai. Eisai Receives Positive Opinion from the CHMP in the European Union for Lecanemab in Early Alzheimer’s Disease. Press Release, Nov. 15, 2024.
2. Pires, M.; Rego, A.C. ApoE4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies. 

 (1), 778.
3. Ono, K.; Tsuji, M. Protofibrils of Amyloid-b are Important Targets of a Disease-Modifying Approach for Alzheimer’s Disease. 

CHMP has granted Eisai Europe and Biogen a positive opinion for the use of their monoclonal antibody therapy in treating early Alzheimer’s disease.