Process Chemistry: Recasting Regulatory Strategies To Enable Green Chemistry

Pharmaceutical process chemists are in a unique position to design and develop chemical processes that not only improve drug efficacy and safety but also are good for the environment and their company’s bottom line—goals that embody the principles of green chemistry.

A significant challenge they face in meeting these goals is addressing regulatory hurdles that govern the approval of new drugs and ensure the quality of drugs already on the market. Such regulations can sometimes stifle process chemistry innovation.

For example, when a new drug enters the final phase of clinical testing, its synthetic procedure is locked into place to ensure consistency. No changes can be made to the procedure without going through a reapproval process. That means companies can be reluctant to make changes, even when a simple one such as switching a solvent can save a lot of money and reduce environmental impact.

The same holds true when a drug has been on the market for several years and a company wants to institute a second-generation manufacturing route. New methods, catalysts, solvents, and purification techniques developed by the scientific community can’t easily be incorporated into the locked-in routes.

Pharmaceutical companies would like some reassurance that, if they do choose to improve their processes, their products would not be at regulatory risk. One concern is being able to capitalize on the investment in making process improvements without fear that changes could lead to the loss of a marketed medicine’s already approved status.

“This is a staggering perceived risk that colors the decisions regarding when or if some firms will invest in green manufacturing routes that could save hundreds of millions of dollars in production costs over the lifetime of a drug,” says John L. Tucker, a senior scientist at biotechnology firm Amgen.

Tucker is a representative of the International Consortium for Innovation & Quality in Pharmaceutical Development (IQ Consortium), a technical working group of pharmaceutical and biotechnology companies founded in 2010 to help advance standards and regulations for the pharmaceutical and biotechnology industries (Org. Process Res. Dev. 2013, DOI: 10.1021/op400192h). In a dialogue between the IQ Consortium and the Food & Drug Administration, agency officials sought to dispel any misconceptions regarding perceived regulatory hurdles and expressed support for efforts to promote green manufacturing of pharmaceuticals.

As an outcome of their conversations, the IQ Consortium and FDA have prepared a document laying out ground rules for the way forward. To read more about the pharmaceutical industry’s efforts and FDA responses on green process chemistry, go to http://cenm.ag/iqcfda.