Clinical trials – credibility issue?

In general clinical trials are important and necessary. It is like in any other area that one has to show that the “things” (in this case, medicines/treatments) work as expected – clinical trials serve such purpose.

However, in medicines area, underlying scientific concepts and practices are extremely poor hence “clinical trials” practices face credibility issue. For example, developing products (tablet/capsule) clinical trials (bioequivalence test – regulatory requirement) are conducted which indeed lack clinical relevance and usefulness. Therefore, it could be argued that such tests indeed expose subjects, often healthy human volunteers, needlessly to potent chemicals in the name of medicines development. (link)

Similarly, relating to Corona virus pandemic, there appears to be rush towards development of medicines/vaccines. It may be argued that as the underlying analytical science is not well-established to monitor virus and/or its “disease” it would be very difficult to conduct appropriate and validated “clinical trials” (link)

In short, running clinical trials is a good idea, however, conducting appropriate and useful clinical trials remains challenging that is where the confusion is.

Can we say?

  1. Flu came and gone!
  2. Why it was called a pandemic – not clear
  3. Discredited the bench top science – as disease state monitored with charts and their shapes (humpy or dumpy) with protocol/testing developed on the fly
  4. Discredited the medicines approval system with the approval of medicines without requiring established protocols
  5. Treatments could be suggested and implemented without having knowledge or expertise in the area of medicine.
  6. Exposed the great weakness, perhaps more accurately ignorance, of “science” at the authorities!
  7. Hope we learnt something not to repeat in future

(1)Coronavirus pandemic: Public/patients deserve better! (link)

(2)Authorities (including FDA) and pharmacopeias (including USP) never establish quality of products! (link)

(3) Is Coronavirus really causing abnormally higher number of deaths? (link)

Coronavirus pandemic: Public/patients deserve better!

The unfortunate situation created by this Coronavirus pandemic is providing a serious opportunity for reassessing the current regulatory approaches in pharmaceutical products development as well as their manufacturing so that in future such irrelevant discussion can be avoided and patients can have access to modern and multiple options to treat ailments. Hopefully in the future patients will be treated with well-established products rather than products developed on the fly or with the use of disposable gowns, masks, washing hands and/or staying home policy which certainly are not the treatments – patients expect and deserve something better from us as scientists, physicians and regulators. Follow the link for complete article (link)

Bye Bye – Bioequivalence testing? Long live drug dissolution testing! —– #2 (gift from heaven)

Yesterday, I posted my view on the recent FDA guidance documents for chloroquine and hydroxychloroquine (link). I do not think people realize the long term impact of this development where BE studies have been replaced/substituted with drug dissolution testing. Let me explain:

  1. Saying that guidances are product specific is not correct, because chloroquine and hydroxychloroquine are drugs not products. Products are tablets, or capsules, with often unknown and proprietary composition of a drug, excipients and manufacturing attributes (i.e. formulation and manufacturing attributes). Hence, guidances cannot be product specific as assumed or suggested.
  2. A drug dissolution test is conducted for products not drugs. As product attributes are mostly unknown and propriety, as noted above, hence a dissolution test (or guidance) cannot be product specific but has to be independent “standard or universal”.
  3. Furthermore, it is to be noted that in principle product specific guidance concept is an invalid concept. Drug dissolution testing is a scale used to measure dissolution characteristics of a product. By definition it (scale) has to be independent to the tested items. Point being that the guidance documents cannot be restricted one or two drug products. These have to be applicable to ALL highly soluble drug products. It would not be possible for authorities, at least scientifically, to defend restricting to only one or two products. This decision could easily be challenged and won.
  4. In addition, such a decision cannot be one time decision, as many believe, may it be taken under an emergency situation. It would not be possible to withdraw such a decision once taken i.e. if dissolution test alone can provide quality assessment of the products, then why would BE studies be needed and required on what basis especially when BE studies are known to be irrelevant (link).
  5. This new development is a gift from heaven for the underdeveloped countries where because of lack of BE studies, products and their manufacturing have always been labelled inferior. However, with the requirement of dissolution testing only, everyone can manufacture and promote (for local and/or international markets) their quality products with confidence.

Keep these thoughts in mind and proceed accordingly.

Bye Bye – Bioequivalence testing? Long live drug dissolution testing!

Recently FDA provided 1- and 2-pager guidance documents for chloroquine and hydroxychloroquine, respectively (link).

The most interesting part is that one can get product approval based on dissolution testing alone. This is what has recently been suggested in one of my recent published articles i.e. products (“quality”) assessment can easily and accurately be established with drug dissolution testing alone (link). There is really no need of conducting bioequivalence (BE) assessments. These (BE) assessments procedures have never been validated of the intended purpose. In fact BE are scientifically invalid and can provide false conclusions and assurance about product quality. In addition, such testing exposes healthy human volunteers to highly potent chemicals under the disguise of medicine development.

On the other hand, switching to dissolution testing alone using currently recommended USP apparatuses is not valid either, at least scientifically. The recommended apparatuses are non-GMP compliant and can provide false and irrelevant results because of their intrinsic design and operation problems. Simpler and scientifically valid options are available and could be used (link).

Crescent-Shaped Spindle

Now Available
Click here