Author: Dr. Saeed Qureshi, Ph.D.

Testing into compliance is a USP/FDA requirement for drug dissolution testing, the only test available and recommended to indicate the quality of the products in a particular tablet/capsule.

The reason for the 3- (or 4-) stage testing into compliance (USP/FDA Tolerance) is because of regulatory requirements of using flawed (also non-validated/non-GMP) dissolution testers and methods which are known to provide irrelevant and unpredictable results. Scientifically speaking, there is no reason to use the currently recommended testers, in particular USP Basket/Paddle, to evaluate the products. Blame the USP/FDA for requiring this testing into compliance practice, not the analysts and/or the companies.

“Quality by International-Culture,” “Designer’s Quality,” “Barrels of Lies,” “Risk/Braggart Analyses,” “Chains of Supply-Lines,” “Quality by Who,” “Quality by Scripts,” “Non-stop Manufacturing,” “Chomping the Provider,” “Bullying the Peasants,” “Pharmaceutically Assumed Technology,” “Curing the Unknown,” “Promoting Deception,” “Spreading Fear,” “Conceit of Acronyms,” “Drumming (fake) Science,” “Observing for Nothing,” “Fun with Data Recording,” “Rotten Desserts with Statistical Toppings” and others (see here and here).

In reality, these are drug products containing medicines or drugs. It is just like candy is not sugar but contains sugar, i.e., candy is a sugar product. The quality of drugs or medicines and their products are two completely different and separate characteristics. However, authorities in ignorance mistakenly describe these as the same. No one, including authorities and pharmacopeias, can determine or establish the quality of such products because the “quality” of such is undefined. Therefore, claims most often made following facility GMP inspections (positive or negative) or regulatory reviews reflecting the quality and by extension, safety and efficacy of the products are simply false. Pay attention to such false claims.

To learn more about the differences between drugs and drug products and how to determine the quality of the drug products, consider attending the upcoming seminar (link)

Regulatory authorities, including pharmacopeias, stated and promoted mandate is to ascertain that consumers and patients receive safe, efficacious, and quality pharmaceutical products such as tablets and capsules. It is important to note that at the commercial manufacturing stage, the safety and efficacy of the products are not usually monitored, only the quality which acts as a surrogate for the safety and efficacy. Therefore, authorities can only claim that they are establishing or monitoring the products’ quality; by extension, products would be considered safe and efficacious. From the industry perspective (both brand-name and generic), it is, in fact, a relatively simple and standard exercise of manufacturing fine chemicals and their composites. They follow the same or similar scientific/manufacturing principles and practices as for manufacturing of any other chemical or its products.

Considering the strong hold of the authorities, manufacturers and distributors can only sell or import/export products that would meet the regulatory/pharmacopeial requirements and/or standards, i.e., they have to comply. In this regard, it should be critical to note that “quality of the products” or “product quality” is an undefined term or parameter, thus, cannot be determined or established. Therefore, claims made by the authorities and/or pharmacopeias for establishing quality are not correct or truthful.

The main reason for this false claim or practice is that the authorities consider and promote compliance as quality, which is incorrect. At present, compliance is not linked to the quality of the products (as it is undefined). However, it is linked to numerous self-created arbitrary, flashy, and catchy phrases (considered as requirements/standards/practices) such as Data Integrity (DI), risk based-assessments, Real World Evidence (RWE), Quality by Design (QbD), Process Analytical Technologies (PAT), regulatory perspectives, precision medicines, patient-centric and many others. However, the fact remains that none of these requirements and practices has any link to the quality of the products (logically or scientifically) as “quality” is an undefined parameter – but confusing and frustrating vocabulary and mumbo-jumbo for regulatory purposes.

This arbitrariness of standards and requirements has choked manufacturing and severely limited access to high-quality products for patients at affordable prices. One of the main reasons for this manifestation is the implementation of arbitrary standards/requirements through facility inspections by “experts” internal or external to the authorities through so-called GMP practices and/or the implementation of other guidelines. Many of these “experts” may, in reality, be characterized as “snake oil salesmen or women” applying “laws” by choosing or picking some “exploitable,” mostly superficial deficiencies (“observations”) to bad mouth the industry and its staff. But, on the other hand, the industry watches this absurdity and humiliation with horror. It does not have any option of being heard that what is required from them is neither relevant nor scientific. The industry has no choice but to bow down to survive – hence the fraud continues with a vengeance and “gained admiration/credibility” of the “experts.”

In short, the public can’t have quality drug products until authorities start setting logical and science-based standards and specifications. As a start, the “quality” of products needs to be defined clearly with a measurable parameter using valid scientific principles. The irony is that if relevant science and its principles are to be followed, these issues can easily be addressed. This would not only result in reducing the regulatory burden but also provide freedom to the industry for manufacturing quality products and open the doors for innovations for affordability and accessibility. I describe such concerns and potential solutions extensively through my blog (link). I would be happy to explain these in person (mailto:principal@pharmacomechanics.com) as well if it helps.

Some suggested blog articles:
(1) Promoting quality standards for drug products: Scientifically speaking, please be systematic and logical! (link)
(2) Possible interpretation of the FDA response to my Citizen Petition – a positive and encouraging development (link).
(3) Pharmaceutical product manufacturing as per current regulatory requirements! (link).
(4) Consumers and patients must wait, and suffer, for the availability of quality pharmaceutical products such as tablet/capsule as well as their genuine and affordable prices. The reason may surprise you! (link).
(5) Comparing Quality Standards – Pharmaceutical vs Consumer Products (link).

Similarly, if you do not know what a “quality product” (screw) is, then there is no point in learning and applying GMP guidelines (screwdrivers). You cannot have relevant and useful guidelines and quality pharmaceutical products. See here for further details.

Need help defining quality products and using scientifically sound methodologies for establishing quality, please contact (mailto:Principal@pharmacomechanics.com).

The stated and promoted mandate of regulatory authorities, including pharmacopeias, is to ascertain that consumers and patients receive safe, efficacious, quality pharmaceutical products such as tablets and capsules. It is important to note that at the commercial manufacturing stage, the safety and efficacy of the products are not usually monitored, only the quality which acts as a surrogate for the safety and efficacy. Therefore, authorities can only claim that they are establishing or monitoring the quality of the products, and by extension products would be considered safe and efficacious. From the industry perspective (both brand-name and generic), it is, in fact, a relatively simple and standard exercise of manufacturing fine chemicals and their composites. This follows the same or similar scientific/manufacturing principles and practices for manufacturing any other chemical or its products.

Considering the strong hold of the authorities, manufacturers and distributors can only sell or import/export products that would meet the regulatory/pharmacopeial requirements and/or standards, i.e., they have to be in compliance. In this regard, it should be important and critical to note that “quality of the products” or “product quality” is an undefined term or parameter, and thus cannot be determined or established. Therefore, claims made by the authorities and/or pharmacopeias for establishing quality are not correct or truthful.

The main reason for this false claim or practice is that the authorities consider and promote compliance as quality, which is incorrect. At present, compliance is not linked to the quality of the products (as it is undefined) but to numerous self-created arbitrary, flashy, and catchy phrases (considered as requirements/standards/practices). They are data Integrity (DI), risk based-assessments, Real World Evidence (RWE), Quality by Design (QbD), Process Analytical Technologies (PAT), regulatory perspectives, precision medicines, patient-centric, and many others. However, the fact remains that none of these requirements and practices has any link to the quality of the products (logically or scientifically) as “quality” is an undefined parameter – but confusing and frustrating vocabulary and mumbo-jumbo for regulatory purposes.

This arbitrariness in setting standards and requirements has choked manufacturing and severely restricted access to actual quality products for patients at affordable prices. One of the main reasons for this manifestation is the implementation of arbitrary standards/requirements through facility inspections by “experts” internal or external to the authorities through so-called GMP practices and/or the implementation of other guidelines. Many of these “experts” may, in reality, be characterized as “snake oil salesmen or women” applying “laws” by choosing or picking some “exploitable,” mostly superficial deficiencies (“observations”), to bad mouth the industry and its staff. On the other hand, the industry and the staff watch and bear this absurdity and humiliation with horror without any options of being heard or reacting. The industry has no choice but to bow down to survive – hence the fraud continues with a vengeance and “gained admiration/credibility” of the “experts.”

In short, it is not possible for public to have quality drug products until authorities start setting logical and science-based standards and specifications. As a start, the “quality” of products needs to be defined clearly with a measurable parameter using valid scientific principles. The irony is that if relevant science and its principles are to be followed, these issues can easily be addressed. This not only would result in reducing the regulatory burden but also provide freedom to the industry for manufacturing quality products as well as open the doors for innovations for affordability and accessibility. I describe such concerns and potential solutions in extensive details through my blog (link) and would be happy to explain these in person as well if it helps. Some suggested blog articles:
(1) Promoting quality standards for drug products: Scientifically speaking, please be systematic and logical! (link)
(2) Possible interpretation of the FDA response to my Citizen Petition – a positive and encouraging development (link).
(3) Pharmaceutical product manufacturing as per current regulatory requirements! (link).
(4) Consumers and patients must wait, and suffer, for the availability of quality pharmaceutical products such as tablet/capsule as well as their genuine and affordable prices. The reason may surprise you! (link).
(5) Comparing Quality Standards – Pharmaceutical vs Consumer Products (link).

In a recently published article (link), titled “FDA Q&A: Generic Versions of Narrow Therapeutic Index Drugs National Survey of Pharmacists’ Substitution Beliefs and Practices” by a Senior Science Advisor, responding to a question regarding concerns expressed in a recently published book, the author of the article claims that “…Americans can be confident in the quality of the products the FDA approves.”

It is to be noted that the claim made by the FDA cannot be considered truthful and/or scientifically valid. The reason is that the quality of the products, in particular tablets and capsules, has not been defined and thus cannot be measured or established. Furthermore, meeting compliance requirements as a substitute of “quality”, which in most cases are arbitrary, lacks validation of the suggested methods and/or procedures (both in vitro and in vivo) for their relevancy and accuracy for their intended purpose or claims (link). Therefore, it is requested that the FDA reconsider its

Response to a recent query

I am sorry I cannot be of help because, in my view, based on 30 years of research experience, as stated frequently, currently recommended and used dissolution testers  (USP Paddle/Basket) are non-validated testers. Hence, they cannot provide any product’s relevant dissolution methods and/or results. Furthermore, developing a discriminating dissolution test, often promoted and suggested as a regulatory/pharmacopeial requirement, is a scientifically flawed or invalid concept. A properly developed dissolution test by default becomes a discriminating test; however, as one cannot develop a relevant and/or appropriate dissolution test at present, thus one cannot develop a discriminating test.

On the other hand, if you like to work with some modified version of a dissolution tester, developed in-house or as I have suggested (with a crescent-shape spindle),. Then, there is a possibility of conducting an appropriate and relevant dissolution test, which will act as a discriminating test too. I will be happy to discuss this approach in further detail if you like to explore this further.

In the meantime, the following blog article may help explore the topic further (link).

They promote and impose fake science, irrelevant and invalid scientific methods, false data/statistical analyses, and foolish manufacturing/inspection practices. This is also creating unscrupulous “experts” and “expertise” in the area, multiplying the damage to the industry, consumers, and patients due to the limited availability of pharmaceutical products and significantly higher costs.

Stuck and suffocated!

Some relevant links: (1, 2, 3, 4, 5)

Below are some posts about the Similarity Factor (F2), which is suggested for assessing the quality of pharmaceutical products using drug dissolution testing.

(1)    F2 – Similarity Factor (Link)

(2)    F2 – Similarity Factor (A Deficiency). (Link)

(3)    F2 (similarity factor) or a 2F (faulty facts) factor (Link)

(4)    F2 – Similarity Factor (Link)

(5)    F2 (similarity factor): An arithmetic skill-test – not a widget for quality assessment of pharmaceuticals. (Link)

(6) Similarity Factor (F2) – false and illusionary “statistics”! (Link)