From The Lab To The Production Plant

If there were any doubts about the importance of chemistry to the pharmaceutical industry, the new drug approvals of 2013 should put them to rest. Of the 27 drugs cleared for marketing by the Food & Drug Administration, 24 were small molecules.

For all the hype in the pharmaceutical world about monoclonal antibodies and other fruits of biotechnology, good old-fashioned medicinal chemistry continues to be a major source of pharmaceutical innovation.

Often that innovation occurs at small, entrepreneurial firms. Typically started by visionary men and women, these companies have great ideas and skilled scientists, but they rarely have the resources to make their molecules at large-enough scale or with consistent-enough manufacturing practices for use in clinical trials.

That’s where contract manufacturers come in. These specialists in pharmaceutical chemical production can make molecules of the quality required by regulators and in the quantity needed for clinical trials.

In the following pages, C&EN presents three stories of pharmaceutical chemical outsourcing partnerships. In all three cases, a small drug company with limited resources has put the fate of a new product in the hands of a contract manufacturer. For two of the companies, this decision was key to getting their molecules among the new drugs recently approved by FDA.

One of the two, Ariad Pharmaceuticals, used deliberate computational and structure-based design methods to come up with Iclusig (ponatinib), which inhibits a mutant enzyme involved in two rare leukemias. Molecule in hand, it turned to Ash Stevens for help in rapidly scaling production for use in clinical trials that would lead to its approval.

Pharmacyclics, the other firm to win FDA approval, brought another cancer treatment Imbruvica (ibrutinib) quickly to market with the help of Lonza, a contract manufacturing partner stretching back to 1999.

The third company profiled, CTI Science, is much earlier in the drug development process. After encountering a roadblock in marketing the antioxidant NBMI as a nutritional supplement, the firm called on PCI Synthesis to bolster its analytical and process design knowledge so it could position the molecule as a mercury poisoning therapy.

Like all companies with a drug in development, CTI faces steep odds. And as scientists at Ariad and Pharmacyclics know, it takes a little luck and a lot of good clinical trial results to get any molecule on FDA’s list of approved drugs.