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.
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