Drug safety testing – a brief look at history
With much of the world’s focus on the Ebola outbreak and the deployment of experimental medicines and vaccines, it’s worthwhile to stop for a minute and think not just about drug and vaccine efficacy, but also about their safety.
When and why did we start caring about drug safety?
The roots of the modern Food and Drug Administration (FDA) are grounded in the 1800s, with interest in drug safety stemming from a surge in counterfeit and contaminated drugs.1
Part 1: Beyond monitoring, quality standards are critical
1846-1848 During the Mexican American War (1846-1848), American troops were prescribed large quantities of medicines, and yet still suffered extremely high mortality rates.2,3 At the time, these deaths were attributed to adulterated foreign drugs, although a general lack of sanitary conditions, bad food, and other infectious diseases were likely more relevant factors.2,3
The result was the Drug Importation Act of 1848, which charged special customs examiners to assess the purity of imported drugs.
While initially highly successful, within two years the act lost its effectiveness, in part due to a lack of quality standards and methods of analysis.3
Part 2: Sterility is not enough to ensure safety
1890 – 1899 Meanwhile, back in the world of medical science, physicians and researchers were trying to follow up on Edward Jenner’s vaccination techniques, but were having difficulties manufacturing inoculant aseptically.4
Even with the bacteriological filters used in the 1890s and the development of sterile ampoules, pyrogenic reactions (fevers) were associated with a subset of vaccination attempts.4
1920 – 1929 It was only in the 1920s that Florence Seibert discovered that heat stable bacterial components contaminated the distilled water used in vaccine preparation, leading to the pyrogenic reactions.5 She developed the first test for these components—the rabbit pyrogen test—and a method for producing pyrogen-free solutions that ushered in a new era of safety for parenterally administered medicines.6
Amazingly, despite the far-reaching importance of these findings, Dr. Seibert is better known for her later work developing the purified protein derivative (PPD) test for latent tuberculosis infection, which is still the gold standard today.
Fast forward to the 21st century
The components Dr. Seibert identified are now referred to as endotoxins, bacterial lipopolysaccherides that make up the cell wall of gram negative bacteria. Keeping endotoxins out of any entity that enters our body parenterally, either a medicine or medical device, is just as important today as it was in the past centuries. However, the test for endotoxins has been updated to the Limulus Amoebocyte Lysate (LAL) assay which is faster, cheaper, and more quantitative than the rabbit pyrogen test. Just as importantly, it does not require the use of live animals to conduct.
A recent case study, “Training to Save Lives: Better Quality Care from Better Quality in the Laboratory,” highlights the work of Associates of Cape Cod, a company that conducts LAL testing for the pharmaceutical industry.
What makes our medicines and medical devices safer than ever before is not only the standardized testing that companies like Associates of Cape Cod provide, but also the quality standardsfor assay reagents, methods, and measurements to which they adhere.
Additional Resources
Learn more about drug safety testing
Download Case Study: “Training to Save Lives: Better Quality Care from Better Quality in the Laboratory”
About the Expert
Pia Abola
Pia Abola is a scientist who walked out of the lab five years ago and stumbled into the world of marketing. She never had to look back because it turns out that she’s mostly doing the same things–both her lab work and her marketing work revolve around signalling and information transfer. Chemical, biochemical, behavioral, or digital signals, the math is the same — it’s just scale and medium that differs.
References
- Wallace F. Janssen. The Story of the Laws Behind the Labels. at https://www.fda.gov/about-fda/what-we-do
- Walch, A. A Spurious Solution to a Genuine Problem: An In-Depth Look at The Import Drugs Act of 1848. (2002). at http://dash.harvard.edu/handle/1/8846790
- David D. McKinney. The Mexican American War Brings Regulation on Drug Importation. at http://www.cbp.gov/sites/default/files/documents/mexicanamericanwar.pdf
- Dean, D. A., Evans, E. R. & Hall, I. H. Pharmaceutical Packaging Technology. (CRC Press, 2005).
- Daniel, T. M. Florence Barbara Seibert and purified protein derivative [Founders of our knowledge]. Int. J. Tuberc. Lung Dis. 13, 281–282 (2009).
- Tim Sandle. Pyrogens, Endotoxin and the LAL Test. at https://www.academia.edu/1802210/Pyrogens_Endotoxin_and_the_LAL_Test
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