NanoViricides Inc. (NNVC)

[arvitar]

Are you saying that there is some less-than-100% measurement whereby fairly reproducible could be reproducible enough for the FDA to find it acceptable?

Sorry - longish answer. But you asked.

No chemical reaction is "100% reproducible" and 100% free from impurities.

Fluctuations in temperature, pressure, the times that each reaction step of a synthesis are allowed to proceed, and impurities within the different chemicals and reagents used in a reaction all contribute to variation. One tries to control these things as best as possible, of course.

When one speaks of "reproducibility", what specific aspects of a chemical synthesis are being referred to. Average particle size? Polymorph variants? Yield of the desired product? The amounts and types of impurities? etc etc.

When one synthesizes a nanoparticle polymer, for example, there will usually be a distribution of different nanoparticle sizes. It won't be the case that every particle in the end product has the exact same size. So the best one can do is give a statistical characterization of particles sizes, such as saying the sizes lie between X-nm and Y-nm in length, the average being Z-nm, show a plot of the distribution of sizes, etc. "Reproducibility" in this case would mean different batches of the material have the same statistical distribution of particle sizes.

Everything I've just mentioned will be different for every different type of molecule being synthesized.

To answer your questions after all of this: The FDA doesn't define required percentages. Everything measured will always be less-than 100%. It is a "negotiable percentage", in that you do what you can under GMP conditions, measure and quantify things, and make sure in your pre-IND meeting that your process will be good enough for the FDA to accept.

Typically, the FDA is most concerned about seeing a characterization of the impurities in the material being tested. They want to see that the percentage and types of those impurities are reliably reproduced between different batches of the material.

If your material, with its characterized impurity profile pass all the IND tox studies, the FDA will want to know that the material being tested in humans has at most those same percentages and types of impurities. In would be okay to make the material "better" than what was tested in IND tox, (fewer impurities or less % of the impurities), but it would be a problem if the material being tested in humans had *different* impurities than what was tested in IND tox.

I don't know what, if anything, additional the FDA requires for nanoparticle therapeutics beyond what is typically required. I'd imagine a characterization of particle size, and reproducibility of size-distribution.