New FDA requirement is driving drugmakers outside the USA

While likely not the US Food and Drug Administration’s intent, the net effect of the agency’s requirements surrounding importation of active pharmaceutical ingredients (API) is driving manufacturing of investigational finished drug products outside the USA, note David Gibbons and Dara Katcher Levy on Hyman, Phelps & McNamara’s FDA Law Blog.

In its most egregious implementation, the FDA’s current interpretation sets up a Catch-22 in which a batch of investigational API cannot be imported for manufacture of finished drug product without an Investigational New Drug (IND), but an IND cannot be obtained without analyses and stability data on that drug product. As a result, investigational API and drug product, from a practical perspective, must be made entirely within or entirely outside the USA. Because API manufacturing is largely done outside the USA, the FDA’s requirements have the effect of encouraging sponsors to manufacture outside the USA to the detriment of pharmaceutical developers, US contract manufacturers and patients, the lawyers point out.

The practical effect is that pharmaceutical firms who wish to import API from outside the USA but manufacture drug product in the USA must undertake at least two separate imports prior to initiation of clinical trials. Even then, however, there are more hurdles. Because imported API for clinical drug product can enter the USA no earlier than the day the IND becomes effective (no sooner than 30 days after submission of the IND), drug product for use in clinical trials cannot be available for use on day 30, when the clinical trial would otherwise be able to begin enrolling subjects. Instead, the clinical trial cannot begin until that API is manufactured into drug product and subjected to sufficient testing for release. Thus, the use of imported API to manufacture clinical trial material in the United States will result in a delay to beginning the clinical trial - a delay imposed by the FDA’s overly rigid interpretation of its regulations. On the other hand, the manufacturer could produce clinical trial material outside the USA in time to import it into the USA and ship it to investigators on day 30, without delaying the start of clinical trials.