Can Regulatory And Pharmacopeial Compliance Practices Establish Quality?

Published today in Pharmaceutical Online (link). If you like to have a pdf file, you can down load it from here.

Hope you will find it interesting and useful.

Discriminatory drug dissolution tests: unscientific hence unlawful

In response to a recent query, I provided the following opinion which others may also find useful.

Your query has two parts: (1) scientific; and (2) regulatory. I will try to provide you my opinion on both and hope that it will work for you.

Scientifically speaking:

(1)    There is no need for developing a discriminatory dissolution test. A valid dissolution test/method becomes a discriminatory test by default which must exist a priori to product development. This is a fundamental scientific principle.

(2)    One cannot develop a dissolution test or a discriminatory dissolution test while developing the product. It does not matter if the product is of immediate release type or anything else.

(3)    At present, an official discriminatory dissolution medium does not exist. A dissolution medium represents GI tract environment, which remains constant for all products (immediate and slow release) i.e. product independent. Therefore, dissolution media cannot be different for different drugs and their products. Requiring such would simply be illogical and unscientific.

(4)    A requirement of product specific dissolution tests should be considered as unscientific. The method has to be product independent; otherwise anyone can “develop” method showing their product as per their liking.

Regulatory (“compliance”) aspect:

(1)    As noted above there is no logical/scientific reason to ask for a discriminatory test and/or its development.

(2)    However, I realize that “experts” including from within regulatory agencies are implementing unlawful requirements as lawful/legal. Governments e.g. US FDA have started taking actions against such practices [1].

(3)    The only suggestion I have, is to request your respective authority to provide an example of officially recognised “discriminatory dissolution medium/method” which you can reproduce for your work/product. That is, a medium/method shown to discriminate between “good” and “bad” products clearly describing the “good” and “bad” products for human use.

You may find a number of articles/blogs on this site ( in support of the above. I hope this will help.

Do FDA bioequivalence and drug dissolution testing guidance documents represent back door law-making?

The recent presidential executive order [1] aims to clarify the practice of developing guidance documents and their implementation. Current guidance documents such as for drug dissolution testing and bioequivalence may come under scrutiny as back door law-making practices.

The law and regulations (such as cGMP) require that the recommended scientific methods should be relevant, qualified and validated for establishing and monitoring quality of the drug products. However, FDA guidance documents ignore these requirements and enforce regulatory requirements by using irrelevant, non-qualified/non-validated testers and methods [2,3].

Calling chemicals, and their composites, as “medicines” does not change their identity and/or nature!

They remain chemicals! Establishing and monitoring quality of these products, such as tablet/capsule, follow fundamental principles of chemical sciences. Currently, these principles are seriously ignored and/or violated under various non-scientific practices such as regulatory guidance/requirements and/or pharmacopoeial standards. Hence, the fact remains that no one is monitoring, or can monitor, quality of these products, no matter how or who presents/promotes it – claims would simply be false.

The manufactures do not have the freedom to manufacture quality products because they have to be in compliance with the irrelevant and non-GMP regulatory requirements and standards.

On the other hand, if “quality” of the products is defined with a measurable parameter which is surprisingly simple and straight forward, it will become much simpler and efficient to establish, monitor and manufacture quality pharmaceutical/medicinal products.

The following links (1, 2. 3. 4) provide some relevant references for further details in this regard.

Why I write, what I write, and the way I write – no offence!

It has become a common practice that people get offended with my postings and comments, e.g. on LinkedIn Forums. This leads to receiving pretty offensive responses on the Forums even blocking me from some discussions. On the other hand, hardly I ever receive any such comments or reactions privately but support and admiration of my contributions described in peer-reviewed journal publications, presentations, seminars, direct advices and consultations as well as on my blog postings.

In my view, my postings are not offensive, or I am not a crackhead with subnormal intelligence to get such impolite responses but it is because that my postings do not fit with the current practices, challenges and the strongly held dogma (in the name of science). I consider this is normal whenever status quo is questioned which my posts are about.

My main concern and view is that the assessment of quality of products and the claims made, including by regulatory authorities and pharmacopoeias, are scientifically untruthful and invalid. Without going deeper into technical details (which are described in my publications and/or on the blog), it can be stated that as quality of the products has never been defined in measureable terms, therefore, it cannot be established and claimed. So, all the claims made in this respect are scientifically false and invalid.
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