Author: Dr. Saeed Qureshi, Ph.D.

As a follow-up to a discussion on LinkedIn Form (link) and my previous posting on this site  (link), posted here is an agreed-upon version (document) of our debate and views (link). I hope visitors to this blog will find this discussion useful for their purpose and scientific advancement in general.

Please, feel free to share your comments or views by sending these to me at (moderator@drug-dissolution-testing.com) or on the LinkedIn Forum of your choice.

Regards

Saeed Qureshi, Ph.D.
moderator@drug-dissolution-testing.com

A follow-up post from LinkedIn Discussion Forum for the visitors of this blog.

With reference to your comment, “Our consensus starting point is that a scientific definition of a quality attribute (we will focus here on rate and extent of drug dissolution) is necessary for QbD. “

For simplicity and clarity sake, I would consider the “quality attribute” in two parts: (1) quality – establishing the patient’s need which is fulfilled by the product (2) attribute – a measurable characteristic that would reflect the quality aspect. For the purpose of our discussion, quality means – a product must deliver the drug as expected (which consumer needs). Note a subtle difference here, but a critical one, that the consumer does not need a product but a drug; however, buys a product to fulfill the need for the drug. So, the quality of a drug product becomes its ability to provide the drug to the patient in an expected manner. As a scientist, we need to acknowledge and fulfill this need of the patient. To answer this question scientifically, we need to define a measurable characteristic of the product showing the deliverability of the drug – this measurable characteristic becomes the quality attribute of the product. In general terms, this quality attribute is known as the product’s drug release/delivery capability. So, in reality, drug release/delivery capability is the quality attribute. Measurement of the quality attribute will depend on the product type, most likely depending on the product’s route of administration. For our current discussion, we will initially start or restrict our discussion to oral products such as tablets and capsules. For oral products, drug release capability (quality attribute) is measured by the drug dissolution characteristics of the product in the GI tract. As drug dissolution is a critical characteristic for assessing oral product drug release/deliverability, it becomes CQA. Please note here that drug dissolution test/testing is not a quality attribute but a test to measure the quality attribute (drug release capability) of the oral products. So, if one likes to move towards QbD, one needs to agree on the terminology of quality and its attribute, followed by its measuring approach. Let me know your views on this aspect, and then we will move further.

Please do not spend too much time thinking or discussing dissolution results, as currently suggested testers and experimental conditions have no scientific basis. In addition, dissolution testing using currently suggested apparatuses, particularly paddle/basket, provides only highly variable, unpredictable, and irrelevant results.

If you do not get the expected or desired results, please keep testing until you get the desired results, which is the pharmacopeial approach of continued testing (S1 to S3) with six units, followed by six more units, and then by 12 units. You will be in a tough situation if you do not meet the test at S3. After that, you might have to make up some clever suggestion/reason to get over this situation so that you can continue this repetitive testing.

In the end, if you have a choice, document that the suggested testers are non-GMP (non-validated/non-qualified). Thus, their use was not further explored. No one can challenge this! Instead, use a more scientifically relevant tester, e.g., see here.