Should claims of quality of approved and marketed drug products be considered valid – not necessarily? Theranos’ style regulatory and pharmacopeial claims!

A product can only be considered of quality, and by extension safe and efficacious, if it meets specification(s) directly linked to a defined quality property/parameter. As, at present, a quality parameter for pharmaceutical products such as tablet and capsule, is undefined thus it is not possible to make valid claims in this regard.

Current regulatory and pharmacopeial approved products available on the market should only be considered as compliant to arbitrary standards/specifications, mostly invalid and irrelevant for quality. Claims are unsupported – a similar scenario as observed in the case of Theranos (link). Please use caution is making or accepting such claims, and seek appropriate help in addressing the issue (link).

Dear regulatory authorities:

Please consider defining a quality product along with its measurable parameter which will make most of the current regulatory requirements and practices unnecessary resulting in efficient manufacturing and significant cost reductions. Please follow the links for further details (1, 2)

“Regulatory (pharmaceutical) science” – lacks logic as well as science!

One cannot establish quality of anything without knowing or defining it first. This is simple logic!
Regulatory authorities including pharmacopeias, however, have been trying to prove this logic wrong! That is, they have been making claims of establishing and monitoring quality of pharmaceutical products such as tablet and capsule – without knowing or defining it. Obviously, they will fail and have been failed!
Logically and/or scientifically, none of the products (approved or otherwise) available on the market can be considered of quality. Guidance and compliance-based system, along with the plant inspections, is a thick smoke screen hiding the reality and hindering the progress.
Please, define a quality product and set the standards and specifications accordingly so that appropriate quality products could be manufacture and monitored. For further detail, please see here.

Selecting medium for drug dissolution testing: Please pay attention to the principles of science and the laws of nature

Considering solubility characteristics of a drug in the stomach (i.e., pH range of 1 to 3) are pretty much useless from the perspective of absorption of a drug. Even if a drug gets dissolved in the stomach, it will be precipitated out in the intestine if it has lower solubility at a higher pH.

For absorption purposes a drug must dissolve, not necessarily completely but in some quantity, in the intestine where pH ranges from 4.5 to 7. Drugs get absorbed in steps in the intestine by continuous extraction process thus complete dissolution of drugs, at any given time (so called “sink condition”) is not necessary.

Moreover, dissolution characteristics are not usually determined for a drug – dissolution tests are conducted to evaluate products. The choice of medium is linked to the physiological environment of the GI tract not to the drugs or products. Please pay attention to the principles of science and the laws of nature. For further detail please follow the link (link).

Simulation and modelling practices for establishing quality of pharmaceutical products – valid intentions but invalid outcomes

Dear experts:

In the area of simulation and modelling, including developers of commercial software for such, note that I may not be able to argue with you regarding your methodologies of data analysis, modelling and/or simulation aspects as this is not my area of expertise; however, I know with certainty that you would require valid and accurate data for your analysis purposes. The difficulty is that you would not have access to such valid and accurate data at least for the evaluation of tablet or capsule products for the prediction of plasma drug levels or profiles. That is, in vitro drug dissolution results which represent or simulate in vivo dissolution and by extension plasma drug levels or profiles. You would require such data to validate your simulation or modelling outcome at least for the product development and manufacturing stages. Unfortunately, no one, at present, is generating, or can generate, valid in vitro dissolution data, thus your efforts of conducting simulation/modelling are regrettably of no use and would not help the industry, regulatory authorities or anyone else. Please, do not make claims of the successes and usefulness of such exercises.

One of the main reasons for not being able to obtain valid in vitro dissolution or drug release data is that the recommended and required (e.g. from USP and FDA) dissolution testers for such purposes have never been shown to provide valid and accurate dissolution results i.e. these testers have never been validated for their intended use or purpose. Vendors/manufacturers make extraordinary efforts and take pride in providing “compliant” testers i.e. meeting or exceeding “physical or fixed” specifications according to the pharmacopeial (such as USP) requirements; however, unable to validate the testers as dissolution testers. For example, no vendor, at present, can provide you valid in vitro dissolution results if given a blinded sample of a tablet/capsule product. Therefore, in this respect claims made by the vendors are also not accurate that they are selling or manufacturing dissolution testers. At best, the only claim they can, or should, make is that they are selling simple stirrers. Perhaps more disturbing is the fact that these stirrers when used as required for dissolution evaluations, because of their design and operation limitations and flaws, cannot provide valid and accurate dissolution results which is documented extensively in the literature.

In short, please use and promote the simulation and modelling techniques with care and certainly use extra caution in making claims for such about the future expectations and successes.

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