Just confirming, the definition of “should” could vary from country to country in the final version, for instance the US FDA versus the EU version. What would you recommend for companies that are international/global? Another person also wanted some practical, down-to-earth words around what “should” should mean. In other words, in here, the person asks, is “should” in ICH similar to “must”, is “should” in FDA similar to “good to do”? In other words, I think there’s a little confusion around “should”.

At least in the United States, the “should” language in any guidance is a safe harbor. If you follow
it, you should be found in GMP compliance. If you do something different than what is mentioned
in Q7A, then you should have information to demonstrate to an investigator that what you’re
doing is reasonable. If you’re doing what the guidance says, the presumption is you’re in
compliance and you’re doing something reasonable.
The intent of the expert working group was that the definition would be the same in different parts
of the world. Both the EU version and the FDA version talk about alternative methods and identify
recommendations. The language is quite clear in both versions. Q7A identifies GMP expectations
or recommendations for API manufacturing. When we talk about GMP requirements, that’s
usually referring to a regulation, which is legally binding. So, if something is spelled out in the
GMP regulation, 21 CFR 211, that’s a requirement, that’s legally binding.
Q7A’s expert work group provided a lot of examples to help identify what we were looking for. It
was not meant to be the only way. If we said, “should”, our intent was that it’s something that
should be done, but you could do it in a different way if there was another option and you would
be able to justify it. The guidance has a lot of flexibility in it to recognize the real world.