Quality assessment of pharmaceutical products – regulatory/pharmacopeial standards and methods require urgent attention!

A patient needs a drug but prescribed or purchases a drug product (such as tablet or capsule) with an implied assurance that product will release the drug in the body as expected to provide its therapeutic effect. This characteristic of drug release/delivery in the body from the product defines the quality of the product.

At the manufacturing stage one hardly ever conducts clinical tests to establish the safety and efficacy of the products but only the “quality” tests. The reason being if the quality is acceptable then safety and efficacy will be acceptable as well because drug levels in the body and safety and efficacy are directly linked.

The tests most often conducted to establish quality of products at the manufacturing stage are the chemical tests, commonly known as in vitro tests. The most common in vitro test which is conducted to establish drug release or quality of the tablet/capsule products is known as a drug dissolution test. This is the only test which forms the basis of quality assessment of tablet/capsule products. Regulatory authorities, including pharmacopeias, worldwide recommend and enforce proper use of this test to establish the quality of the products. There are numerous guidance documents available from the regulatory authorities, including US FDA, which describe the requirements of the dissolution testing procedures forming the basis of drug product approvals.

The important, and perhaps a very disturbing, fact to note here is that the dissolution testers, along with associated methods, as recommended by the authorities have never been validated for their intended use or relevance. In fact, many scientific studies (e.g. link) have clearly shown that the tests do not and cannot provide relevant results i.e. the testers cannot provide accurate results/data regarding the products (tablet/capsule) quality. Therefore, any claims made regarding the quality of the approved products by anyone, including authorities, lack accuracy and scientific authenticity.

The regulatory authorities enforce extensive set of requirements and standards through elaborated set of “compliance” guideline such as ICH or US FDA guidance documents for establishing quality of the products. This guidance-based compliance system is directly or indirectly dependent on the drug dissolution test at least for tablet/capsule products. Therefore current guidance-based system is not only providing false assurance about the quality of the products but also causing severe hindrance for the industry to produce quality products appropriately and efficiently. In addition, this guidance based system adds enormous administrative burden for both, authorities and manufacturers – unfortunately of no or limited benefit to either party. Furthermore, as the recommended testers are non-qualified/non-validated which makes them non-GMP compliant, thus authorities could easily be found in violation of GMP practices – potentially a serious and disturbing claim. Therefore, this deficiency should be addressed on an urgent basis with the highest priority.

It is important to note that scientific studies have clearly shown that currently recommended apparatuses have a design problem which could be corrected by simple modification. Suggestions have been made in the literature in this respect addressing the issues. Further information in this regard may be obtained from here.

In short, authorities should take a note of this critical deficiency which exists in the drug product approval requirements caused by requiring non-GMP drug dissolution testers. This deficiency needs to be addressed quickly so that quality of the manufactured products could be established and monitored accurately and efficiently.

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