Quality of pharmaceutical products: “Regulatory Science” – its illusions, obstacles and a potential solution.

“Regulatory Science” is a term often used to describe practices of national, sometime international, bodies to establish and monitor quality of pharmaceutical products such as tablet and capsule, which would include safety and efficacy aspects as well. A clear description of the term “Regulatory Science” appears to be lacking. In practice it may be considered as a practice of setting standards (specifications) and protocols for describing and establishing quality of products available on the market for human use. The underlying concepts for setting standards/specifications and protocols usually come from the fundamental principles and laws of sciences, engineering and mathematics such as biology, chemistry, manufacturing and statistics. “Regulatory Science” uses these scientific principles to set specifications and protocols, rather than generating new scientific knowledge which is generated under the auspices of a specific scientific and/or engineering discipline. Therefore, regulatory bodies hardly ever generate new scientific knowledge but use it to generate specifications and standard procedures for implementation for the public good. The authorities also get the mandate to enforce the developed and suggested specifications and protocols – as these are intended to be followed. This mandate of enforcement results in the term “compliance” i.e. industry must adhere (“compliant”) to the standards and protocols for their manufactured products to be approved for marketing. Read the rest of this entry

Time to rescind the regulatory requirements of bioequivalence evaluations and the current pharmacopeial drug dissolution practices as these do not provide quality assessment of pharmaceutical products

Considering the non-specificity, because of confounded variabilities from the physiological system, drug release assessment of pharmaceutical products (tablet/capsule) for which this test is conducted, the bioequivalence test becomes a scientifically and statistically in-valid practice. See here for further discussion on the topic (1,2).

An in vitro drug release test, commonly known as drug dissolution test, which by its nature avoids the above mentioned non-specificity, provides a better alternative for assessing drug release characteristics of the products thus their quality. Pharmacopeias worldwide recommend this test. Unfortunately the recommended testers suffer a serious design problem thus providing irrelevant and unpredictable results not reflecting product quality or lack of it (3,4). In short, the drug dissolution tests as currently recommended are based on non-qualified and/or non-validated testers, hence results from the testing cannot be relied upon. Therefore, their use is to be discontinued as well.

As a solution, a simple revised dissolution testing approach has been suggested which would provide superior drug release evaluation thus quality of the products for human use (5, 6). In addition, as it is an in vitro technique, the test can be conducted without the use of human subjects avoiding unnecessary risk to participating healthy volunteers and/or patients. The suggested approach not only provides scientifically valid method for assessing quality of the pharmaceutical products but also would give much needed flexibility to pharmaceutical industry for innovation to bring out products faster, and with a reduced price, into the market.

Quality generic products without bioequivalence (BE) assessment – a simple and practical approach!

Considering the weakness (non-specificity) of BE assessments it is suggested that in vitro drug dissolution/release testing would provide a better alternative to establish quality of pharmaceutical products such as tablet and capsule. It is argued that the use of in vitro dissolution test should be the method of choice for developing and monitoring improved or better quality generic products because BE assessment focuses only on equivalence and not on the improvement of the product quality. Other significant advantages of using an appropriate in vitro dissolution test in lieu of BE assessment are described..
For further detailed explanation please follow the link.

Pharmaceutical products quality and bioequivalence assessments – what a waste and needless use of human subjects!

A bioequivalence study is conducted in humans to establish that two or more products are capable of providing same/similar blood/plasma drug levels. Underlying assumption is that if the products provide same plasma drug levels then their therapeutic effects would be the same as well, thus would allow interchangeability of the products such as the generics.

Therefore, for all practical purposes the bioequivalence assessment may be considered as a typical analytical chemistry test where the assessment is based on determining plasma levels. For conducting an appropriate and accurate analytical test, the test must follow some fundamental principles of analytical tests such as specificity and its validation (accuracy, precision and reproducibility). A test cannot be validated if it is not specific.

In this regard, a bioequivalence test is a non-specific test as plasma drug levels include (confounded) variabilities from stomach emptying/motility and liver metabolism of the drug – independent of the product characteristics. Therefore, caution is warranted in establishing quality of the test products based on the bio-equivalence test.

For further detailed explanation please follow the link.

Pharmaceutical product manufacturing as per current regulatory requirements!

Consideration should be given for simplicity and appropriate regulatory involvement as current practices and requirements certainly appear anti-innovation as well as making products less accessible and expensive to buy. For further discussion on the topic please follow the links (1, 2, 3).

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