This article presents a practical view on QbD (Quality by Design) approach and its implementation. It is argued that, the critical component of the approach, the defined “quality” attribute to be achieved is lacking. To address this issue, from the consumer/patient perspective the quality of a tablet/capsule product may be defined as availability/release of the drug in an expected amount and manner. However, the technique most often used (known as drug dissolution testing) to evaluate such quality has been recognized to be flawed. Therefore, it is highly unlikely that the QbD approach as presented will be successful in providing improved quality of the products. Suggestions are made for addressing the issues for a potentially successful implementation of the QbD practice. Please click here for complete article

A set of slide presentations from FDA Scientists at the “Advisory Committee for Pharmaceutical Science and Clinical Pharmacology” held on August 8, 2012. (link)

Impressive and highly complicated and complex material. Unfortunately, crescent shaped spindle (http://www.drug-dissolution-testing.com/?p=1136) and simple convolution approach (http://www.drug-dissolution-testing.com/?p=601) did not make it up to there, perhaps it was too simple and straight forward in concept which may actually solve the issues highlighted in the presentations.

Well may be the next time!

In a recent interaction on a LinkedIn group “Quality-by-Design” under “All it will take is the development of a relevant dissolution method!” I posted a response which I thinkl would be useful to the visitors of this site. Please click here to see the post. Hope you will find it useful.

As a fundamental principle of science, this should be quite obvious that one should NOT develop or use product dependent methods or parameters to characterise the product itself. However, this is precisely the practice in the pharmaceutical area for product development and/or its evaluation i.e. everyone seeks/develops and uses a product dependent dissolution method.

This is clearly an example of a mindset which is obviously incorrect and scientifically invalid. It appears that this mindset has been created by the practice of pharmacopeial testing. Most pharmacopeial tests (e.g. USP) are drug and/or product dependent, however, these should be considered scientifically invalid or useless. The reason being that if a dissolution test is product dependent, then, it will not be possible to establish whether observed dissolution characteristics are because of the product or due to the experimental conditions used. Therefore, it should be noted that one cannot rely on product dependent (e.g. pharmacopeial) methods to establish dissolution characteristics of a product, thus its quality.

To evaluate the quality of a drug product, the dissolution method must be product independent. Therefore, developing product dependent dissolution methods for any purpose i.e. QC, discriminatory, bio-relevant, IVIVC, bio-waiver, QbD etc should be considered a mistake and complete waste of time and resources.

At present, vessel based dissolution tester with crescent shape spindles (link) has been suggested for product independent dissolution testing, thus not only it provides unbiased and scientifically valid dissolution testing, but also help in saving large resources.

Commonly described dissolution methods are product dependent. Therefore, it is not possible to know whether the observed dissolution characteristics are a reflection of the product (formulation and/or manufacturing) attributes or because of the experimental conditions (apparatus, rpm, medium etc.) employed.

For an appropriate and accurate assessment of dissolution characteristics of a product, the dissolution method must be product independent. The use of crescent shape spindle has been suggested based on this principle, thus provide true dissolution characteristics of a product. Please see the following links, for further discussion:

(1) http://www.drug-dissolution-testing.com/?p=449#more-449
(2) http://www.drug-dissolution-testing.com/blog/files/Flyer.pdf
(3) http://www.drug-dissolution-testing.com/?p=826
(4) http://www.drug-dissolution-testing.com/?p=1136
(5) http://www.drug-dissolution-testing.com/?p=1061#more-1061