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It has become very difficult for life science researchers and assay developers to find suitable antibodies for their work. Currently, there are > 300 companies marketing > 3.5 million antibodies to the research community. The majority of these antibodies are relabelled copies whereby an antibody vendor purchases an antibody from another manufacturer / vendor and relabels / repackages the antibody for resale - with these trade sales facilitated by OEM agreements.

Example:

HyTest produce a mouse monoclonal [6C5] antibody to GAPDH. This antibody is relabelled for resale and marketed by thirteen antibody vendors including:

  • Abcam | Anti-GAPDH Antibody [6C5] | ab8245
  • Bio-Rad | GAPDH Antibody | MCA4739
  • Merck Millipore | Anti-GAPDH Mouse mAb (6C5) | CB1001
  • Novus Biologicals | GAPDH Antibody (6C5) | NB600-502
  • Santa Cruz Biotechnology | GAPDH Antibody (6C5) | sc-32233
  • Thermo Fisher | GAPDH Monoclonal Antibody | AM4300

The Extent of Relabelling:

Dr Jan Voskuil (CEO of Aeonian Biotech) highlighted the extent of antibody relabelling at the 1st International Antibody Validation Forum in 2014. He used Biocompare to search for antibodies to Transcription Factor FOXP3. Biocompare returned 1055 antibodies from 47 antibody vendors - Jan studied these antibodies by comparing their attributes and QC data. He learnt that out of the 1055 antibodies available there were only 31 unique antibodies on the market.





Negative Effects:

Despite being great business for the companies involved, this practice is incredibly detrimental to biomedical research as it results in:

  • Increased product prices (up to 400%, per unit quantity).
  • Inaccurate and misrepresentative datasheets.
  • Decreased independent product validation.

Increased Prices: Spot the Difference?





A) Abcam | Anti-GFAP Antibody | ab7260 | 50µl | $429 | £279

B) EnCor Biotechnology | Anti-GFAP Antibody | RPCA-GFAP | 50µl | $120 | £165

C) GeneTex | GFAP antibody | GTX27260 | 50µl | $369 | £299

D) Merck Millipore | Anti-GFAP Antibody | AB5804 | 50µl | $298 | £261

E) Novus Biologicals | GFAP Antibody | NB300-141 | 50µl | $369 | £247

F) Thermo Fisher | GFAP Antibody | PA3-16727 | 50µl | $375 | £326

Apart from price there is no difference between these antibodies - they all orginate from the same antibody made by EnCor Biotechnology (RPCA-GFAP) and are simply relabelled / repackaged for resale. For more examples, please see our Price Comparison article.

Misrepresentative Datasheets:

It is now common for relabelled antibodies to be listed with out-of-date, unrepresenatative datasheets. The following extract, written by Jan Voskuil, explains how:

"The vast majority of vendors do not manufacture all the antibodies on the catalogue, and most of their antibodies have been obtained from a wide variety of different manufacturers from all over the world under OEM agreement (Other External Manufacturer). Such an agreement usually has a clause to forbid the supplier from publishing which of their products are sold by their OEM vendor. The vendors keep up the appearance that they themselves are the primary source of all their antibodies. This enables them to keep QC data on the product sheet that were generated many years ago thus keeping the sales going, while the actual antibody that generated these data may have sold out and has been replaced by successive other batches (from different animals) and the current batch on sale may no longer be able to generate such data at all.

Even monoclonal antibodies suffer from batch-to-batch variations, but not to such severe extent as some types of polyclonal antibodies. Nonetheless, certain hybridoma clone numbers are still being used for decades while, just like with cell lines, hybridomas cannot be the same after so many passages. It is misleading to use QC data that were generated decades ago, unless the current batch has proven to still be capable of generating such data (in which case one might as well show the latest version of the data).

Vendors accrue data from their own customers or from their own QC department, thus making the OEM product look unique. This way the same antibody can show different QC data on different catalogues. And while batches run out and are being replaced by others, it can happen that a vendor still has some of the old batch in stock, while another vendor will keep the QC data obtained from the former batch on their product sheet. From this moment on customers start to buy products that are no longer necessarily reflected by their product sheet.

Vendors do not only obtain their antibodies from the original manufacturers. There is a network of vendors obtaining each other’s catalogue items. Consequently, the same antibody starts to occur several times in one catalogue: one time with the current QC data provided by the original manufacturer and one or more times with QC data obtained from the other vendor’s direct customers or QC department. Potentially, assay developers buy several antibodies from several vendors thinking they are buying different antibodies, yet a number of them originate from the same manufacturer’s catalogue number."

When antibody vendors obtain antibodies externally, they receive a spreadsheet containing product specifications from the OEM / antibody vendor they are sourcing the product lines from. The antibody vendor uses this information to create the product specifications and datasheets for their relabelled versions. It is common for product attributes (i.e. immunogen, storage buffer, Clone ID's, etc..) to be manipulated, in order to help a product appear 'unique', and for attributes (i.e. isotype, etc..) to be accidentally modified.

For example, Epitope Biotech Inc produce a mouse monoclonal [FG4R] antibody to FLAG Tag. This antibody is relabelled for resale and marketed by sixteen antibody vendors including:

  • Abcam | Anti-DDDDK tag antibody [FG4R] | ab125243
  • Arigo Biolaboratories | anti-DDDDK antibody [FG4R] | ARG62342
  • Novus Biologicals | DYKDDDDK Epitope Tag Antibody (FG4R) | NBP2-37823
  • Thermo Fisher | DYKDDDDK Tag Monoclonal Antibody (FG4R) | MA1-91878 | 14-6681-80

The isotype of this antibody is IgG1, however, Abcam advertise the isotype of ab125243 as IgG2b, Novus Biologicals advertise the isotype of NBP2-37823 as IgG2b and Thermo Fisher advertise the isotype of MA1-91878 as IgG2b and the isotype of 14-6681-80 as IgG2b, kappa.

There is a large network of vendors obtaining antibodies from each other, and if one vendor makes a mistake - it is echoed across the whole market. In this case, Clonegene advertise a relabelled version of this antibody with the isotype IgG2b - which could be the root of the problem.

Decreased Independent Product Validation:

The practice of relabelling antibodies decreases the amount of independent product validation data available - as this information is split across several dozen 'unique' antibodies each identified by a seperate product code.

For example, Epitope Biotech Inc produce a mouse monoclonal [HA.C5] antibody to HA Tag. This antibody has been cited in two publications and has been validated by Epitope Biotech Inc for use in Dot, WB, IP, IS and ELISA. This antibody is relabelled for resale and marketed by twelve antibody vendors including:

  • Abcam | Anti-HA tag Antibody [HA.C5] | ab18181 | ab127427
  • GeneTex | HA tag antibody [HA.C5] | GTX18181
  • Origene | Anti-HA tag monoclonal antibody | TA100012
  • Santa Cruz Biotechnology | HA-probe (HA.C5) | sc-57595

Taking into account relabelled versions of this antibody - this antibody has been cited in 40 publications and been validated for use in ChIP/Chip, WB, ICC, IP, ICC/IF, Dot, ELISA and In Situ Hybridization.

It is interesting to note that Origene market this antibody as only validated for WB, whilst Abcam market ab18181 as validated for ChiP/Chip, WB, ICC, IP and ICC/IF and market ab127427 as validated for IP, ICC/IF, ELISA, Dot, WB and In Situ Hybridization - despite the fact that all these antibodies originate from Epitope Biotech Inc's Anti-HA Tag Antibody.

The Relabelling Racket:





References

1. Economics of reproducibility in pre-clinical research.

2. Drug Development: Raise standards for preclinical cancer research.

3. 1,500 scientists lift the lid on reproducibility.

4. A Genecentric Human Protein Atlas for Expression Profiles Based on Antibodies.

5. Reproducibility: Standardize antibodies used in research.

6. 1st International Antibody Validation Forum 2014: Jan Voskuil.

7. Reproducibility crisis: Blame it on the antibodies.

8. Abcam Annual Report 2016.

9. Sigma Aldrich Annual Report 2014.