There is no possibility of establishing quality of products without fixing the pharmacopeial drug dissolution test!

Quality of a drug product, such as tablet and capsule, may be defined as product’s ability to release the drug in humans in expected amount and with consistently. In technical term, it is known as drug release characteristics of the product. At the manufacturing stage, this characteristic is established by conducting an in vitro test commonly known as drug dissolution/release test. The test is commonly conducted as recommended by regulatory agencies (such as FDA) and pharmacopeias (such as USP) using paddle and basket apparatuses. The quality assessment of most of the solid dosage forms, if not all, in particular tablet and capsule products is determined using this test.

The testers for this test, however, have never been validated for the intended purpose. Therefore, conclusions drawn from this test, hence quality of the products, would be invalid and false. Use caution in accepting and/or making claims about quality of products! (link)

Seek help for conducting a scientifically valid drug dissolution test and establishing quality of the drug products.

Sink condition – an invalid and unscientific concept and requirement!

Drug dissolution testers, in particular most commonly recommended ones (paddle and basket), are based on closed system/environment i.e. without a drain, therefore, it is not possible to have or create a sink condition. Authorities and pharmacopeias require it while “experts” create it. How? Magic!

In addition, one does not even require a sink condition for in vitro drug dissolution testing. 900 ml of water with or without a small amount of solubilizer sufficient to (freely) dissolve the expected amount of drug present in the product – is all one needs. For further details please follow the link here to simplify your life and avoid wasting time and resources (link).

Quality Fraud!

One cannot avoid being part of it. It is the regulatory agencies’ (e.g. FDA) and pharmacopeias’ (such as USP) practices and requirements to use the non-validated/non-qualified (hence non-GMP) testers and tests causing the fraud. Any claim with respect to quality of the products, in particular tablet and capsule for both brand-name and generic products, has to be false.

Blaming and punishing the industry for product quality and manufacturing are not relevant or valid and would not help. Education, advice and help are needed at the authorities and pharmacopeias in defining quality and setting its standards and specifications (1, 2).

I will be happy to explain the issues with quality assessments in detail and can provide solutions to address them (link).

FDA response during today’s meeting on …

“Understanding How the Public Perceives and Values Pharmaceutical Quality” link

During today’s presentation ( @ 1:58), responding to a question from the floor concerning the use of drug dissolution methods at the FDA, Dr. Cindy Buhse stated that they use USP methods. Unfortunately, it seems that Dr. Buhse does not realize that USP methods are based on non-validated/non-qualified (hence non-GMP compliant) dissolution testers in particular most commonly recommended ones i.e. paddle and basket apparatuses. Inclusion of a test or tester in the USP does not make it valid or qualified. Validation requires scientific/experimental evidence showing that the testers are good/fit for the intended purpose, which these testers lack.

Scientific studies have clearly shown that these testers do not, and cannot, provide relevant and valid results. It would, therefore, be requested that all the results obtained using these testers should be considered null and void and be removed from products quality evaluations. Furthermore, it should be noted that there is Citizen Petition under consideration at the FDA requesting the withdrawal of these testers, and corresponding tests, from the regulatory use (link).

Beware of GMPiers!

These are often visitors to manufacturing facilities under the titles of investigators, inspectors, auditors, consultants, experts, compliance officers, etc. (internal or external to the regulatory agencies). Logically and scientifically speaking, at present, they provide absolutely no useful or valuable purpose for the development, manufacturing and assessment of pharmaceutical products such as tablets and capsules but hindrance, delays and exuberant cost to industry and by extension to consumers/patients. Their observations and conclusions are based on subjective and narrative discussion not on any scientific, measurable or quantifiable assessments. Most often, their outcomes are filled with fancy catch phrases or acronyms such as cGMP, validations, CSV, data integrity (DI), record-trailing, inappropriate SOPs, improper documentation, root cause analysis, CAPA, which in general are book/record keeping (admin/clerical) exercises mostly unrelated to quality of the products and/or quality of the manufacturing. Read the rest of this entry

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