Regulatory requirements for establishing quality of pharmaceutical products – serious scientific and cGMP deficiencies and flaws!

[I posted the following comments on a discussion on the AAPS Community Forum. I think visitors to this website would also find it a helpful read].

Thanks for your comments in response to my post. I am unsure how I should respond because your comments focus more on philosophy than subject matter.

Indeed I worked with Health Canada as a research scientist to support and criticize the assignments’ underlying scientific aspects. Most of my laboratory work has been published, and views have been known publically as well – as you noted. I have never undermined any ones’, including authorities’, hard work or practices.

However, through my laboratory work and related applied experience, I did find some very disturbing misunderstandings about the use of science for the quality assessment of pharmaceutical products. Drug dissolution testing is one part of it; the second, more noticeable, is the claims of establishing the quality of the manufactured products, particularly tablets and capsules. These misunderstandings should be highlighted and addressed, in my opinion, not be ignored and concealed; otherwise, everyone involved in it will lose their credibility, in particular scientific, for a long time to come.

Your statement, “We, working in the industry, have worked very hard trying to make it work.” I am sorry, what does it mean? Can you determine the dissolution characteristics of a given blinded product sample? Have you used a validated dissolution tester for dissolution testing? How? How could you or anyone else develop a valid dissolution method without the availability of a validated dissolution tester? Can you define and establish a product’s quality using the drug dissolution method? How? Please, note that the quality of the products is not yet defined with a measurable parameter. Then how could a dissolution test be used as a quality control tool? These are some unanswered questions about using flawed science and its practice in manufacturing and regulatory assessments. These questions are not directed toward you as a person but at the industry and regulatory authorities in general. I do not know how to direct my concerns only to the regulatory authorities. I do not think that AAPS Community Forum is only for the industry. I observed it is equally read and participated in by the regulatory scientists. A discussion was just started on this community forum by a scientist from FDA (e.g., see under METHODS IN IMAGING DATA ANALYSIS).

So please join hands with me and inform the regulatory authorities that there are severe problems in regulatory requirements rather than a suggestion of avoiding discussions of these issues. This would not be public service or service to patients but something else!

You noted from my post, “A dissolution method should not be used for product development until and unless it has been clearly shown ………….” This is not my view or my suggested requirement – this is a general principle of science and regulatory (i.e., cGMP) requirement. If anyone is not following or meeting this requirement, then the results obtained would not, at least should not, be accepted under (cGMP regulation. As an example, I quote the following three FDA regulations for your information [21 CFR 111.320, 21 CFR 820.72, 21 CFR 211.194 (a) (2)]. Please correct me if I am wrong on this.

In the end, please consider using this forum to inform the authorities that fundamental scientific principles, as well as cGMP requirements, are being violated, which need to be addressed so that the industry could be able to function appropriately and the public should receive accurate and honest information about the quality of the manufactured pharmaceutical products.

I will be happy to help anyone explain the issues and suggest possible solutions to such if you suggest or provide leads in this regard. I look forward to future fruitful discussions on the subject with you.

With best regards

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