The London-based European Medicines Agency (EMA) issued the document in July, changing a section relating to starting materials in an explanatory note covering active pharmaceutical ingredient (API) manufacturing.
The revised reflection paper makes clear that if a chemical intermediate being used to make an API is an API the applicant can submit the certificate of suitability (CEP) – as well as details of manufacturers involved - instead of a detailed process description.
The new document also states that if the intermediate is already in an approved drug and documented in an ASMF, the applicant can reference the document.
The original reflection paper, published in 2014, defined “starting materials” as the first substance used in the production of an API and stressed that such compounds need to be produced in accordance with good manufacturing practice (GMP) standards.
However, while the terms were clear, the problem according to the European Medicines Agency (EMA) is that drug manufacturers and national regulators often disagree on what constitutes a starting material as a result of flexibility built into ICH Q11 guidelines.