Q. How closely does FDA expect API manufacturers to adhere to ICH Q7 for GMPs?
ICH Q7 itself provides guidance regarding cGMPs for the manufacturing of APIs under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the quality and purity characteristics that they purport, or are represented, to possess. Legally, FDA considers ICH Q7 to be the equivalent of "guidance." FDA guidance documents are quite helpful and typically explain the agency's interpretation of laws and regulations, often describing acceptable means and methods that would comply with the law and that may be considered best practices. Although guidance documents are not legally binding, following them is highly recommended. FDA cannot enforce guidance nor will it specifically cite departures from guidance in regulatory communication. The agency enforces the law and properly promulgated regulations that have the force and effect of law. How then is ICH Q7 used by FDA in the regulation of API manufacturers?
The Federal Food, Drug and Cosmetic Act Section 501 (21 USC 351) states that a drug (whether the drug is a finished pharmaceutical or a component of a finished pharmaceutical) is considered adulterated if "...the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice..."(2). For finished pharmaceuticals, the cGMP requirements are clear—the agency promulgated cGMP regulations for finished pharmaceuticals in 21 CFR 210/211 (3).
The agency has not established cGMP regulations for APIs. Nevertheless, APIs must still meet the provisions of the law and be manufactured in conformance with cGMP. But without regulations, what is considered to be cGMP for an API? The answer, for all practical purposes, is ICH Q7 is considered to be cGMP for an API. Closely following its provisions will not only help ensure your APIs are safe, pure, and potent, but following its provisions will also help ensure your APIs are not considered to be cGMP-adulterated.
1. ICH, Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (November 2000).
2. Federal Food, Drug and Cosmetic Act Section 501 (21 USC 351).
3. 21 CFR 210/211.