How High-Quality Monoclonal Antibodies Combat 'Antibody Anarchy'

We all depend on antibodies to stay healthy^1,2 — antibodies recognize infectious invaders in the body, such as bacteria and viruses.^1,2 They also play a crucial role outside of the body and in the clinic by helping physicians make medical diagnostic decisions,^1,3 and even in the laboratory for research and product development.^3,4 When antibodies don’t work as expected, the problem of ‘antibody anarchy’ causes unnecessary trouble for healthcare professionals, patients and even scientific researchers working to confirm experimental results.^3,4   The consequences of such problems can be far reaching, affecting more than scientific invalid results.  Medix Biochemica produces high-quality, validated IVD antibody products that are extensively characterized and able to counteract antibody anarchy.⁴

For decades, antibodies have played a crucial role in diagnostic tests, and in research for product development.^3,4 But what happens when these valuable tools are revealed to be less reliable than expected? A lack of proper testing and validation before launching an antibody product can have serious consequences.^4,5,6,7

Since the antibody used determines the performance and accuracy of diagnostic tests, partnering with a trusted supplier of specific, reproducible antibodies ensures that you get accurate, consistent and trustworthy results time after time.⁴

Understanding 'antibody anarchy'

To successfully detect a disease during diagnostic testing, an antibody must have the right sensitivity (ability to recognize clinically relevant levels of a substance) and specificity (ability to bind a specific target).⁴ The term ‘antibody anarchy’ refers to the problems that arise when an antibody doesn’t have these qualities and therefore doesn’t yield accurate results.^4,5

Common examples of antibody anarchy include:

• Lack of specificity and sensitivity: The antibody developed isn’t specific, and unexpectedly binds to multiple targets other than the intended target^4,5. This is known as the ‘cheating reagent.’⁵
• Lack of consistency: The originally developed antibody is of good quality, but the cell line has been poorly developed and soon becomes non-viable, making it impossible to reproduce the antibody.⁴ As a result, after numerous experiments have successfully shown specific findings, the same experiments using a new antibody batch no longer reproduce those findings.^4,5 This is known as ‘lost treasure.’⁵

In other words, the supplier may have developed and launched an antibody product that hasn’t been properly characterized for specificity and/or hasn’t been properly developed to be a viable long-term commercial product.⁴ 
It’s cause for serious concern when antibodies sold for diagnostics and research don’t work as efficiently as their suppliers claim they do.⁴

The cost of unreliable antibodies

What do unreliable antibodies mean for patients and healthcare providers and the IVD industry?

• A patient who should test positive may get a false negative result,⁴ meaning they don’t get the care they need and their disease goes undetected until it has advanced and become difficult to treat.⁶
  
• A patient who should test negative may get a false positive result,⁴ leading to unnecessary treatment or hospitalization.⁷
  
• False positives and false negatives may affect tracking and studies on the prevalence of a disease. This may put unnecessary strain on hospitals or mean that an illness is under/over-reported.^6,7
  
• Medical findings may be invalidated and have to be retracted.^4,5
  
• The  harm caused to patients as a result of inaccurate results may lead to legal action.⁶
  
• Possible hardships for test kit manufacturers due to recalls, scrapped finished materials and delayed time to market.
  

In short, antibody anarchy can have a far-reaching clinical, legal, financial and emotional impact.^5,6,7

Book time with a Medix Biochemica expert to learn more about our antibody products.

How do we combat antibody anarchy?

1. Stringent validation practices

Proper validation – proving suitability for an intended purpose – is essential when developing an antibody for use in a regulated environment like diagnostic testing.^4,8,9. This validation process requires specific laboratory investigations⁸ to prove that the antibody is specific, selective and reproducible in the context in which it will be used.⁸

Successful investigations need to go beyond standard testing, studying multiple samples across multiple batches to determine whether the antibody will continue to work as predicted.^4,8

Thorough validation also involves testing by multiple operators, to prove that all laboratory professionals will always get the same results.⁴

2. Reliable monoclonal antibodies

A monoclonal antibody (MAb) is derived from an animal immunized with the pathogen or foreign protein being targeted.^4,10 Cell biology experts collect the cells that produce these antibodies and isolate the unique cell type that produces a specific high-affinity antibody.⁴  Because a MAb was originally a single cell which was then multiplied or cloned, the same antibody – specific to its target – can be produced over and over again.⁴

In contrast, a polyclonal antibody (PAb) is a mixture of antibodies taken from animal serum, containing several different antibodies which the animal’s system has produced in response to the pathogen.⁴  This mixture can be affinity purified so that most of the antibodies present are specific to the target, but even specific, good-quality PAbs run the risk of inconsistent results from one batch to the next.⁴

In terms of antibody anarchy, PAbs by nature have higher heterogeneity than MAbs, which makes PAbs a less reliable option. ^4,10

Recombinant MAbs, produced by in vitro cloning, are considered to be especially reliable, with excellent reproducibility.^4,11 The DNA that encodes the antibody is extracted from the original cell line and sequenced so that it’s available in digital form. Once the original information is digitally stored, it can be repeatedly reproduced as needed.⁴ 

MAbs From Medix Biochemica

At Medix Biochemica, producing MAbs is our core expertise.⁴ We produce high-quality antibody products that have been validated to ensure specificity, sensitivity and reproducibility.⁴

When skilled cell biology experts, such as those on the Medix Biochemica team, develop a high-quality monoclonal cell line, we mitigate the problem of batch-to-batch inconsistencies ⁴ – we’re able to keep reproducing the same antibody from its original master cell bank, year after year. ⁴

Our reliable recombinant MAbs give you the tools to produce high-quality, accurate and reliable diagnostic tests.⁴ Our products are highly trustworthy and some have been in use for up to 40 years.⁴

The Medix Biochemica approach: an antidote to antibody anarchy

At Medix Biochemica, we use the best technologies to ensure that the antibodies we provide are specific and reproducible.⁴ Our commitment to quality means we’re trusted by some of the in vitro diagnostics industry’s largest global clients. ¹²

From the first moments of thorough and careful new antibody development, we have the end goal of consistent bulk manufacturing in mind.⁴ We develop the cell lines to be stable and completely monoclonal, without any unwanted specificities.⁴

We put a great deal of time and effort into R&D, meticulously designing our selection criteria, testing for cross-reactivities and selecting the right monoclonals for the job.⁴

We also work with our colleagues within the IVD industry to compare and assess new technologies aimed at antibody characterization.¹⁴

Quality is at the core of everything we do at Medix Biochemica, so we don't release any material until it’s qualified for activity, content and identity.¹³ We also conduct extensive testing and follow stringent quality-control processes after manufacturing each batch.⁴ For example, unlike some other suppliers, Medix Biochemica goes the extra mile by checking the immunoreactivity of every batch.⁴  

Over the past five decades, our catalog has grown to include products suitable for assay development, validation and commercialization.¹³ These products are used in human and veterinary diagnostics.¹³

Our trusted antibody products are used in billions of tests worldwide¹³ and we look forward to reliably serving the healthcare diagnostics sector for decades to come. 

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References:

1. What is an antibody? Medical News Today. Accessed January 16, 2023. https://www.medicalnewstoday.com/articles/what-is-an-antibody.
2. Antibodies: definition, types & function. Cleveland Clinic. Accessed January 16, 2023. https://my.clevelandclinic.org/health/body/22971-antibodies.
3. Siddiqui MZ. Monoclonal antibodies as diagnostics; an appraisal. Indian J Pharm Sci. 2010;72(1):12-17. doi:10.4103/0250-474X.62229.
4. Expert opinion. Interview with Laura-Leena Kiiskinen, Vice President Innovation and Business Development, Medix Biochemica. November 21, 2022.
5. Baker M. Antibody anarchy: a call to order. Nature. 2015;527(7579):545-551. doi:10.1038/527545a.
6. Petticrew M, Sowden A, Lister-Sharp D. False-negative results in screening programs. Medical, psychological, and other implications. Int J Technol Assess Health Care. 2001;17(2):164-170. doi:10.1017/s0266462300105021.
7. Healy B, Khan A, Metezai H, et al. The impact of false positive COVID-19 results in an area of low prevalence. Clin Med (Lond). 2021;21(1):e54-e56. doi:10.7861/clinmed.2020-0839.
8. Bordeaux J, Welsh AW, Agarwal S, et al. Antibody validation. Biotechniques. 2010;48(3):197-209. doi:10.2144/000113382.
9. Weller MG. Ten basic rules of antibody validation. Anal Chem Insights. 2018;13:1177390118757462. doi:10.1177/1177390118757462.
10. Lipman NS, Jackson LR, Trudel LJ, et al. Monoclonal versus polyclonal antibodies: distinguishing characteristics, applications, and information resources. ILAR J. 2005;46(3):258-268. doi:10.1093/ilar.46.3.258.
11. Bradbury ARM, Plückthun A. Getting to reproducible antibodies: the rationale for sequenced recombinant characterized reagents. Protein Eng Des Sel. 2015;28(10):303-305. doi:10.1093/protein/gzv051.
12. Our customers. Medix Biochemica. Accessed December 27, 2022. https://www.medixbiochemica.com/our-customers.
13. Antibodies / Antigens / Enzymes. Medix Biochemica. Accessed December 27, 2022. https://www.medixbiochemica.com/antibodies-antigens-enzymes.
14. Madren, S., McElroy, W., Schultz-Kuszak, K., Boumajny, B., Shu, Y., Sautter, S., Zhao, H.C., Schadock-Hewitt, A., Chumsae, C., Ball, N., Zhang, X., Rish, K., Zhang, S., Wurm, C., Cai, S., Bauer, S.P., Stella, C., Zheng, L., Roper, B., Michels, D.A., Wu, G., Kocjan, B., Birk, M., Erdmann, S.E., He, X., Whittaker, B., Song, Y., Barrett, H., Strozyk, K., Jing, Y., Huang, L., Mhatre, V., McLean, P., Yu, T., Yang, H. and Mattila, M. (2022), Global intercompany assessment of ICIEF platform comparability for the characterization of therapeutic proteins. ELECTROPHORESIS, 43: 1050-1058. https://doi.org/10.1002/elps.202100348