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Logical Biological, biospecimen and critical raw material leader, and Bcell Design, pioneers in transgenic monoclonal antibody technology, today announced a long term strategic partnership to deliver engineered disease state materials for diagnostic and research markets.

 

Working together, the two companies will develop customised engineered disease state and ‘spiking’ materials to deliver compelling alternatives to native disease state plasma. Materials are designed and formulated to bring native disease state plasma-like performance, aligned and customised to customer’s performance and scale requirements.

 

Bcell Design is a leading manufacturer of high-quality, human Fc antibodies using a proprietary platform technology. These antibodies are designed to replicate performance of native disease state plasma, and are already used in FDA approved and CE marked platforms by top 10 IVD companies.

 

Logical Biological brings deep expertise in sourcing, processing and providing biological specimens and bulk disease state plasma, alongside custom plasma processing and protein purification capabilities through sister company Logical Antigen. The company is already supplying native disease state plasma and customised critical raw materials at scale to the largest QC calibrator and control manufacturers.

 

Disease state plasma is a key component for IVD calibrators and controls, assay development and quality control testing. However, human disease state materials can be difficult to reliably and consistently source. To solve this challenge, engineered materials are formulated with Bcell Design’s patented human Fc monoclonal antibodies to mimic disease state plasma. This provides multiple benefits – including reproducibility and long-term supply sustainability – whilst maintaining high performance levels and offering benchmarking against native plasma samples.

 

The strategic partnership will focus on IgM and IgG engineered disease state material for challenging to source materials, including Rheumatoid Factor (RF). By the end of 2025, the companies expect to have well characterised products for ToRCH, infectious diseases and other conditions.

 

Léone Atayi, Chief Executive Officer at Bcell Design, commented: “The diagnostics sector faces increasing challenges in securing reliable and sustainable sources of disease state materials. By joining forces with Logical Biological, we are combining complementary expertise in antibodies and plasma materials to deliver sustainable, high-performance diagnostic solutions in key therapeutic areas—supporting earlier and more accurate disease detection worldwide.”

 

Stephane Argivier, Chief Executive Officer at Logical Biological, said: “This strategic partnership will unlock new opportunities and address sustainability for the diagnostics sector. By replicating critical plasma performance characteristics and providing comprehensive performance data, our engineered disease state materials aim to match native plasma performance whilst providing supply security and consistency in specific applications. Building on our bulk purification and disease state material expertise, we’re excited to partner with Bcell Design to help our customers resolve today’s challenges and bring tomorrow’s innovation.”

 

This unique end-to-end solution addresses the requirements of the largest users of native disease state materials, aiming to deliver engineered alternatives with long term supply sustainability and consistency at scale. With bespoke products, the partnership is able to meet customer specifications with extensive testing on multiple platforms and dilutions levels.

 

To learn more about how engineered disease state materials can strengthen quality control manufacturing, visit: www.logicalbiological.com/engineered-disease-state-plasma/

Blog Overview

September 10th 2025
Company News Quality Controls
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Understanding the challenges of obtaining high-titre materials

High-titre biological materials play a vital role in the development and manufacturing of in vitro diagnostic (IVD) controls and calibrators. These materials are essential for accurate and reliable diagnostic tests – a crucial part of patient care and treatment decision-making. However, sourcing bulk high-titre disease state materials presents significant challenges for Quality Control and Calibrator Manufacturers. These obstacles impact downstream processes for IVD companies, and more importantly, the patients who awaiting testing, diagnosis, and treatment.

 

To better understand the challenges, their impact, and potential solutions, we spoke to Brian Fernandez, Biotech Consultant-IVD Specialist, and Andrew Conner, Procurement Director at Logical Biological. Read on to explore their perspectives and practical solutions for those working in the IVD procurement and supply chain sector.

 

Why are high-titre materials becoming harder to source?

“In R&D, you need everything from negatives to high positives to validate an assay. But in manufacturing, the goal is reliability: a consistent, secure supply chain to meet mid-term needs.” Andrew told us. This contrast underscores the sourcing challenges bulk manufacturers face in a regulatory and operational landscape that demands consistency over variation.

 

However, several factors are making sourcing high-titre biological materials more challenging to collect:

  • Advances in treatment reduce availability: Improved medical treatment has created a paradox for the IVD industry. While these improvements benefit patients, they also diminish the presence of key biomarkers in the population. For example, rheumatoid factor (RF) and antibodies linked to infections like human immunodeficiency virus (HIV) and hepatitis C virus are suppressed in many treated individuals, making high-titre samples harder to find.
  • Short-lived antibodies narrow the collection window: Antibodies such as immunoglobulin M (IgM), crucial for detecting early-stage infections, appear transiently and typically decline after seroconversion to immunoglobulin G (IgG). As Andrew explained: “By the time someone seeks care, the IgM window may have already passed. That makes pinpointing this phase more opportunistic and uncertain.”
  • Geographical and ethical constraints: Some disease-state materials, like HIV-2, are predominantly found in specific regions such as West Africa. This geographic limitation, coupled with the need for ethical, consent-based sourcing, narrows the available pool. Many countries restrict or prohibit compensated donation, but this adds another layer of complexity for global procurement. As Andrew mentioned, “You need that outreach to find active infections at different levels, and that often means looking beyond Europe and North America. However, it has to be regulated, consented, and equitable, especially when vulnerable populations are involved.“
  • A quality-first manufacturing culture: Manufacturers often exercise caution when switching suppliers or materials, especially under stringent regulatory frameworks. Minor adjustments like blending or spiking to meet titre levels can trigger validation requirements, which increase both time and cost.

 

Bench to bedside: The impact on Control and Calibrator Manufacturers, HCPs, and patients

The scarcity of high-titre materials directly affects Control and Calibrator Manufacturers, healthcare providers (HCPs), and ultimately, patients.

 

Production delays and rising costs: Scarcity of high-titre materials leads to smaller batch sizes, escalating costs per unit and complicating planning cycles.

 

Brian Fernandez, an experienced professional in the control and calibrator space, shared the challenges he faced first-hand:

“I recall running into difficulties sourcing disease state plasma for RF, antistreptolysin O and total immunoglobulin E quite frequently. The result is that we would adjust our bulk sizes down to accommodate, which could have supply issues with our finished products. In the worst-case scenario, even with drastic volume reductions, we couldn’t reach our intended high-level target. That not only put us at risk of releasing a non-conforming finished good, but also meant that end users lacked quality control materials capable of truly challenging the upper dynamic range of their assays.“

 

This real-world example illustrates the delicate balance procurement teams must maintain between availability, quality, and regulatory compliance.

 

Quality assurance and regulatory hurdles: Regulators often mandate that controls represent native patient samples. Shifting to synthetic materials is a long-term consideration, but not always viable in the short term. “Everyone knows these native materials are getting harder to source. The real question is: when do we move toward synthetic — and are we ready to validate that shift?”, added Andrew. Subsequently, manufacturers may find themselves forced into suboptimal interim solutions.

 

Patient impact: Disruptions in quality control can result in delayed or inaccurate diagnoses, affecting patient care. For clinicians, this means uncertainty, while for patients, it can mean delays to treatment.

 

The Logical Biological difference

At Logical Biological, we are committed to being a trusted partner in sourcing sustainable, high-quality biological raw materials for control and calibrator manufacturing.

Global outreach

Our extensive and growing network currently spans 45 clinical collection sites across five continents, providing access ethically to a diverse range of materials. As Andrew noted, “Certain infections appear only in specific regions. Without a global network, you’re cut off from that biology, full stop.”

Quality assured

We prioritise a rigorous onboarding process for new collection centres, including regulatory vetting, quality assessments, and donor consent protocols.

Ethically obtained

We ensure ethical material collection practices by ensuring all collection centres have the necessary documentation.

Secure supply chain

Our logistics partners maintain high standards, using temperature-controlled shipping methods to preserve sample integrity during transportation and ensure high-titre materials remain free from bioburden.

Meeting evolving demands

Market requirements evolve rapidly, and demand can change overnight. As Andrew noted, “We track historical trends, so when we see a spike, like dengue recently, we’re not surprised we’re ready.” Our approach allows us to evaluate feasibility within 48 hours, developing comprehensive plans from 7–14 days.

Exceptional service

Through proactive planning with our clients, we offer clear communication on feasibility, logistics, and lead times. Our collaborative approach benefits every stakeholder by bringing the right expertise to bear on a customer challenge.

 

Logical Biological: A reliable, global partner in a complex market

Sourcing high-titre biological materials is a difficult but essential process. Our global network makes us a reliable partner for sourcing high-quality material. It means we can address both current and future customer demands while meeting both operational and regulatory requirements with confidence.

 

Contact us if you are facing challenges with sourcing high-titre or rare biological materials, or to discuss how we can support your business.

Blog Overview

May 21st 2025
Opinion Quality Controls
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When it comes to manufacturing quality controls (QCs), choosing the right raw material is essential. Controls need to be accurate, reliable, consistent, and closely mimic real patient samples. But with factors like supply consistency and sustainability, cost, stability, and performance to be considered, how do you decide whether a native or synthetic biological raw material is best? This article explores the advantages, disadvantages, and provides expert insights on selecting the best approach for quality control development.

 

Understanding Native and Synthetic Raw Materials

Native Biological Raw Materials

Native raw materials are biological substances derived from humans or extracted from human-based materials such as native antigen extracts, tissues, cells, blood, serum, plasma, and other bodily fluids. These materials undergo minimal processing to preserve their functional integrity, making them highly relevant in research, therapeutic applications, and diagnostic testing.

Examples of Native Materials:

  • Defibrinated human disease state plasma processed to resemble serum.
  • Natively derived biofluids (e.g., serum, plasma) formulated with purified native analytes like proteins, enzymes, or antibodies to achieve required concentrations.

Synthetic Biological Raw Materials

Synthetic raw materials are engineered biological substances designed to mimic or enhance the functionality of native biological counterparts. They are produced using molecular biology techniques and can offer advantages in terms of stability, scalability, and purity.

Examples of Synthetic Materials:

  • Synthetic plasma or serum matrices made from buffers, polymers, or animal-derived components.
  • Recombinant proteins (e.g., antigens, enzymes, synthetic antibodies) produced via genetic engineering.
  • Modified biomolecules incorporating chemical cross-linking to achieve desired performance or enhance stability.

 

Evaluating Native vs. Synthetic Raw Materials: A Comparative Analysis

To support informed decision-making, the following provides a comparative analysis outlining the advantages and disadvantages associated with native and synthetic raw materials:

Feature Native Raw Materials Synthetic Raw Materials
Biological Relevance High, often more commutable with patient samples May differ from native samples, depending on complexity
Functionality Maybe superior for complex multimeric proteins, cofactors, and post-translational modifications May lack certain native functionalities, but can be optimised
Lot-to-Lot Consistency Natural variability due to biological differences High consistency across batches
Scalability Limited, depends on biological sourcing More easily scalable for high production volumes
Risk of Contamination Potential for human pathogens and biological contaminants Lower contamination risk, free from human pathogens
Ethical Considerations Ethical considerations when sourcing from human donors, particularly high-titre materials from patients No human donor concerns
Stability & Purity Variable stability and risk of degradation if not stored properly Generally, more stable and higher purity
Cost & Availability Can be cost-effective but may be limited by supply Expensive to develop but offers greater availability
Development Time Readily available providing access to suitable donors is sustainable Longer initial development and scale-up time

 

Expert Insights: Native Materials and Their Unique Advantages

One of the most critical factors when selecting raw materials for quality controls is ensuring that they mirror actual patient samples in their response to assay system changes. Experts note that native materials often provide better commutability, meaning they exhibit similar shifts and biases to patient samples when instrument performance, reagents, or calibrators change.

One of our industry experts shared an example where a human-derived cholesterol control detected an assay issue, while an animal-derived control failed to flag the problem. This highlights a key benefit of using native materials—ensuring that quality control samples respond to system variations in the same way as real patient samples.

However, native materials present several challenges, including biological variability, limited scalability, and potential contamination risks. Some complex proteins, such as haemoglobin tetramers and various growth factors, require precise folding, complex subunit assembly and/or post-translational processing, which can be difficult to replicate outside of the natural host organism.  While synthetic biotechnology techniques continue to improve, some proteins are still best sourced through their native sources.

 

Synthetic Materials: Achieving Consistency and Scalability

Synthetic and recombinant materials provide greater consistency and scalability, making them attractive alternatives when native materials are costly or difficult to obtain. Recombinant proteins and synthetic matrices eliminate pathogen risks and offer batch-to-batch consistency.

However, some synthetic raw materials lack key post-translational modifications (PTMs) or require complex folding that native systems inherently achieve. Certain recombinant antibodies, for instance, may not perfectly replicate the native structure due to difficulties in assembling heavy and light chains with correct disulfide bonds. Mammalian expression systems can mitigate some of these issues but add to production costs and complexity.

 

Making the Right Choice: Practical Considerations

Functionality vs. Feasibility

  • If functional integrity and biological relevance are the top priorities, native materials may be preferable.
  • If lot-to-lot consistency and large-scale production are essential, synthetic materials should be considered.

Cost and Supply Constraints

  • Native materials may be cost-effective when high-titre sources are available but can be limited in supply.
  • Synthetic materials often require high initial investment but ensure consistent availability in the long run.

Testing in Feasibility Studies

A practical approach maybe to evaluate both native and synthetic options during feasibility studies. As one industry expert advises:

“I believe there is still a perceived superiority of native materials in quality control development. However, if synthetic options provide cost or availability advantages, I will include them in my feasibility studies and assess their performance. Sometimes, synthetic options can outperform native materials in cost effectiveness, availability, and even performance!”

 

Conclusion: Striking a Balance Between Native and Synthetic

The decision between native vs. synthetic raw materials depends on a careful balance of biological relevance, scalability, and cost. While native materials often provide superior functionality and commutability, synthetic materials offer greater consistency, scalability, and reduced contamination risks.

The debate between native and synthetic raw materials will likely continue, but by understanding their strengths and limitations, QC manufacturers can make informed decisions. Whether you’re using native or synthetic biological raw materials, the right choice depends on your specific needs and the parameter being tested.

Blog Overview

March 19th 2025
Opinion Quality Controls
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Understanding the Challenges of Quality Control Manufacturers

IVD manufacturers face a range of challenges when sourcing biological raw materials. Each manufacturer has unique requirements based on the specific assays and controls they produce, making the selection process highly nuanced. The need for consistent, scalable, and high-quality raw materials is critical, yet these attributes can be difficult to guarantee due to the inherent variability of biological sources.

Lot-to-lot consistency ensures that Quality Control (QC) manufacturers can maintain consistent analyte target concentrations in their products, facilitating smooth validation processes and ensuring regulatory compliance. This article explores the key considerations for QC manufacturers in achieving lot-to-lot consistency when utilising bulk biological raw materials.

 

The Importance of Lot-to-Lot Consistency

For a QC manufacturer, obtaining multiple samples across multiple lots of raw material is critical for qualification and validation purposes. The primary concerns include:

  • Consistent Analyte Values: QC manufacturers must ensure that each lot of material maintains expected analyte concentrations, enabling laboratory personnel to perform accurate patient testing. Variability in analyte values can result in regulatory challenges and usability issues.
  • Reliable Availability: Uninterrupted supply of biological raw materials ensures that QC manufacturers can meet demand and avoid backorders due to material rejection.
  • Scalability: As QC manufacturers expand their market share, the ability to scale raw material supply without compromising quality is crucial.

 

Requirements for Raw Materials

Lot-to-Lot Consistency

Ensuring lot-to-lot consistency is essential to maintaining QC product performance. Variability in raw material specifications such as titre, analyte concentration, and pH can lead to significant manufacturing disruptions. If a batch of raw material falls outside of predefined specifications, it can result in product rejection, requiring costly deviations and re-validations.

Raw material suppliers must implement validated manufacturing processes to guarantee uniformity. By maintaining strict quality controls, suppliers help QC manufacturers achieve seamless transitions when onboarding new lots of control materials.

Reliable Supply Chain

A dependable supply chain is vital for ensuring that QC manufacturers receive raw materials in a timely and stable manner. Delays in raw material shipments can cause backorders, disrupting production and impacting end users. Global shortages of certain biological materials have, in the past, forced manufacturers to implement deviations or retrospective validations—costly challenges that highlight the importance of a supplier with robust inventory management and production planning.

Scalability and Growth

As QC manufacturers expand their market share, their need for increased raw material volumes grows. A supplier’s ability to scale production in tandem with demand is an important factor. Without the capacity to meet growing requirements, manufacturers may face interruptions or be forced to qualify alternative materials mid-production—an expensive and time-consuming process. Scalability ensures manufacturers can confidently plan for future needs without compromising product integrity.

Certificate of Analysis and Stability Testing

A comprehensive Certificate of Analysis (CoA) that includes testing of critical parameters is an essential requirement for QC manufacturers. This ensures that each lot meets established specifications and reduces the risk of unexpected performance issues.

Biological raw materials must maintain stability over time to ensure consistent performance. Real-time stability testing assesses parameters such as titre, activity, concentration, and microbial contamination over a defined shelf-life. If materials degrade over time or accumulate contaminants, they may no longer be suitable for QC applications, leading to batch rejections, customer complaints, backorders, patient safety issues, and increased costs.

Sampling and Retain Program

QC manufacturers benefit from suppliers who implement robust sampling and retain programs. These programs serve multiple purposes:

  • Design and development validation: While raw materials are not typically subject to the same stringent design controls as medical devices, they must undergo validation to support product claims.
  • Validation Processes: At least three lots of raw materials are typically required for design and process validation, making access to multiple retained lots a significant advantage.
  • Troubleshooting: Retained samples enable QC manufacturers to investigate and resolve potential issues efficiently.

 

Technical Considerations for Quality Control Manufacturers

Certain technical challenges can complicate the use of biological raw materials in QC applications. Understanding these issues helps manufacturers make informed decisions.

Protease Activity and Analyte Stability

Protease activity can degrade sensitive analytes in many QC materials. It may originate from microbial contamination and may persist despite efforts to eradicate, neutralize or filter out the microbes. Proteases may also arise from endogenous sources from delayed or improper processing leading to lysis of cells prior to the separation of the plasma/serum component.  Once active, these enzymes can reduce analyte stability and compromise test accuracy.

Albumin Conformation and Stability

Denatured or partially denatured albumin is a lesser-known but significant problem in serum-based products. The three-dimensional structure of albumin plays a crucial role in maintaining analyte stability. Exposure to heat, pH shifts, or denaturing compounds like urea, guanidine or organic solvents, can alter this structure, causing analytes to bind unpredictably. Partially denatured albumin may bind analytes such as hormones, peptides, and enzymes, causing analyte loss and inconsistencies in QC products. Even slight misfolding can lead to assay discrepancies across different instrument platforms, making consistent albumin conformation a critical consideration.

Co-Morbidities in Disease State Materials

Disease state materials often contain a complex mix of cross-reactive antibodies, which can lead to unexpected interferences in QC manufacturing. Ensuring that disease state specimens meet specific inclusion criteria is essential to maintaining product reliability.

Inactivation Processes and Their Trade-Offs

Some inactivation processes, such as heat treatments used to eliminate proteases, can have unintended consequences. While effective at reducing protease activity, these treatments may also denature critical proteins, reducing marker titres and affecting overall performance. Understanding the impact of inactivation techniques on raw material integrity is key to selecting suitable specimens.

 

The Value of Validated Processes

Robust processes that preserve biological raw material integrity are essential for ensuring consistent, reliable performance of QC manufacturers controls and ensuring commutability across different instrument platforms. Selecting the right raw material from the outset minimises the need for costly reformulations and process deviations.

At Logical Biological, we are committed to working closely with our customers to define customised specifications that deliver the performance and consistency their applications demand. Our vision is to provide Insightful Solutions that Make a Difference—ultimately contributing to Improved Health Outcomes.

To turn this vision into reality, we have made significant investments over the past year, in new, expanded state-of-the-art laboratory space, broadening our R&D capabilities, and scaling up our processes and operations. These advancements strengthen our ability to support Quality Control and IVD Assay manufacturers with a sustainable, high-quality supply of critical biological raw materials—ensuring they can meet both operational and regulatory requirements with confidence.

Blog Overview

February 17th 2025
Quality Quality Controls
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Company News Quality Controls

Logical Biological and Bcell Design Announce Strategic Partnership for Engineered Disease State Materials
September 10th 2025
Logical Biological, biospecimen and critical raw material leader, and Bcell Design, pioneers in transgenic monoclonal antibody technology, today announced a long term strategic partnership to deliver engineered disease state materials for diagnostic and research markets.
Read More
R &D Scientist formulating engineered disease state materials