A patient needs a drug but is prescribed or purchases a drug product (such as a tablet or capsule) with an implied assurance that the 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 is that if the quality is acceptable, then safety and efficacy will also be acceptable because drug levels in the body and safety and efficacy are directly linked.
The tests most often conducted to establish the quality of products at the manufacturing stage are the chemical tests, commonly known as in vitro tests. The most common in vitro test conducted to establish drug release or quality of the tablet/capsule products, is known as a drug dissolution test. This is the only test that forms the basis of the 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. Numerous guidance documents are available from the regulatory authorities, including the US FDA, which describe the requirements of the dissolution testing procedures forming the basis of drug product approvals.
The important and perhaps very disturbing fact to note here is that the dissolution testers and associated methods 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 an extensive set of requirements and standards through an elaborated set of “compliance” guidelines such as ICH or US FDA guidance documents for establishing the quality of the products. However, this guidance-based compliance system is directly or indirectly dependent on the drug dissolution test at least for tablet/capsule products. Therefore the current guidance-based system is not only providing false assurance about the quality of the products but also causing severe hindrances for the industry to produce quality products appropriately and efficiently. In addition, this guidance-based system adds an 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 that 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 note this critical deficiency in the drug product approval requirements caused by requiring non-GMP drug dissolution testers. This deficiency needs to be addressed quickly so that the quality of the manufactured products can be established and monitored accurately and efficiently.