An important era in pharmaceutical development occurred 35 years ago with the FDA approval.
The FDA approved human insulin in genetically engineered bacteria which is the first recombinant DNA medication project in the world. This story is remarkable in few ways. One of which is the fact that the regulators and the drugmakers were in unknown territory.
Furthermore, the regulatory review and the development of this medication progressed rapidly and smoothly.
The Canadian researchers Charles Best and Frederick Banting first made insulin in crude form in 1922. That lifted the death sentence which had previously been imposed on people with diabetes.
By the end of 1922, the medication company Eli Lilly and Company had developed a method for higher purification.
Over the following 50 years, the purified insulins obtained from cow and pig pancreases, different from the human insulin by their chemical composition, refined their performance and improved in purity.
In early 1970’s, a new and potent tool, recombinant DNA technology, also known by the name ”gene-splicing” and “genetic engineering” became available. It served as a promise of unlimited insulin which was the same as the molecule made by humans.
One 1973 research article reported about this seminal molecular engineering experiment. The authors of the researchers were the academic scientists Herbert Boyer and Stanley Cohen.
What they did is that they isolated a DNA ringlet by the name “plasmid” from a bacterium, with the help of some enzymes in order to splice a gene from another bacterium to the plasmid. And then they introduced the chimeric or recombinant DNA in E.soli bacteria.
With the recombinant bacteria reproduced, the plasmids with foreign DNA propagated and made amplified amounts of the recombinant DNA.
Furthermore, since DNA has the genetic code which directs proteins and their synthesis, the new methodology promised that it is able to direct cells or genetically modified bacteria in order to synthesize the wanted proteins in big amounts.
Lilly saw the promise which provided this technology for making quantities of human insulin in bacteria.
After obtaining from Genentech, Inc the recombinant E.coli bacteria which had a genetic blueprint for and which synthesized human insulin, they made processes for the large-scale cultivation and the formation and purification of the insulin.
Insulin had been the flagship product of Lilly, and the expertise of the company was evident in the clinical trials, purification, and laboratory testing.
The scientists of the company verified that the product was identical when it comes to human pancreatic insulin. In 1980 the clinical trials of this human insulin began, and the great thing was that this product performed splendidly.
There were no issues with the treatment of certain patients who never previously received insulin injections. Or with those who switched from animal insulin to human insulin.
The dossier with evidence of efficacy and safety was submitted to the FDA in May 1982.
Over the years the FDA had had immense experience with medications from different microorganisms, and with insulins. Therefore the decision was that there is no need of new regulatory paradigms in order to assess the recombinant human insulin.
To be more precise, the recombinant DNA techniques were seen as the refinement, extension of familiar and long-used methods for producing medication. This proved to be a precedent-setting and historic decision.
The FDA approved the human insulin in October 1982, on the basis of exhaustive review of the data of Lilly’s from clinical trials in thousands of people with diabetes. And also pre-clinical testing in animals.
The average time from approval for new medications is around 30 months. However, this approval and review took only around 5 months. No medication, produced with new technology, had been approved that fast.
This introduced an era which within few decades would witness recombinant-DNA derived medications and those made with monoclonal antibody technology dominate medication development.
Sales on an annual basis are in hundreds of billions. Also monoclonal antibody and recombinant DNA-derived medications are in the top 10 sales leaders regarding the pharmaceutical sector.
However, the fast human insulin approval was not the start of a trend toward the regulatory enlightenment. Now, bringing a new medication to the market takes from 10 to 12 years and costs more than $2.5 billion.