As a part of a discussion (link) on the LinkedIn Network group (Quality-by-Design), I posted the following response. For the interest of people who do not participate in the LinkedIn Network or the particular group, I am posting the response on the blog as well. I hope that you will find the post useful.

I think it is a critical and very important topic (FDA Seeks Metrics to Define Drug Quality, link) i.e. defining metric(s) for establishing “quality” of pharmaceutical products. This has also been my view, and it has been stated on this forum a few times as well, that one cannot determine, monitor and/or improve “quality” of a drug product until it is clearly defined (for example, see links, 1, 2). That is, what is a “quality product” and what parameter should be measured to reflect this “quality”.

My interest/expertise lies in the area of solid oral dosage forms (e.g. tablet/capsule products), where the “quality” of a product may be defined as achieving expected and consistent levels of drug in blood/plasma or body. Therefore, assessing plasma drug concentration-time profiles (aka bioavailability/bioequivalence) becomes a “quality” metric for solid oral dosage forms.

However, because of ethical, time and financial reasons/constraints this parameter cannot be used on a routine basis for manufacturing purposes. Therefore, an in vitro surrogate of concentration-time profiles is required. Drug dissolution testing is that surrogate, with very valid scientific reasons, and has been in use precisely for this purpose for many years.

The most unfortunate and ironic part is that the test itself is scientifically valid, however, the way testing has been done, or required to be done by standard setting organizations, is scientifically and logically invalid and useless. There are at least two reasons which make the current practices invalid: (1) persistent requirement of using dissolution apparatuses/testers which have never been validated for dissolution testing purposes. In fact, suggested/recommended testers, in particular paddle/basket, are flawed and are incapable of providing dissolution results of any product (link); (2) most, if not all, dissolution methods are product dependent, thus cannot provide unbiased or “true” dissolution characteristics of the products (link).

Using a slightly modified dissolution tester along with a suggested simpler method development approach can resolve such issues and would help in defining and monitoring the needed “quality” metric for the solid oral dosage forms (link).