Impact of the revised USP Chapter <1058> [Analytical Instrument Qualification - AIQ] on the pharmacopeial drug dissolution testing – the beginning of the end of the use of current dissolution apparatuses including Basket/Paddle!

Recently USP revised the above mentioned chapter (https://tinyurl.com/y9wdfl58) to clarify AIQ terminologies including the definition of Design Qualification [DQ]. There is nothing new in the description that should not have been clearly understood by both – the users and manufacturers of the apparatuses including their service providers. However, confusion exists in the minds of analysts and manufacturers who consider that testing and re-testing of the fixed parameters are the qualification, calibration and/or performance verification steps. The chapter clearly describes that such fixed parameters never need to be retested or re-established. With regards to drug dissolution apparatuses, the so called mechanical calibration and/or meeting of the specifications as described in the USP dissolution chapters <711> and <724> would fall in the fixed parameters category, therefore, would never require testing or re-testing. Read the rest of this entry

Product specific guidance for generics – a scientifically invalid concept/practice

The purpose of generic products, such as tablet and capsule, evaluation is to establish that the two or more products containing the same drug provides the same/similar plasma profiles of the drug -independent of their formulation and manufacturing attributes. Thus, evaluation or testing must be product-independent. If requirement and standards are based on product specific attributes, then these would not be applicable for other products, including generics, as they could have different attributes (formulation/manufacturing). Product specific testing and standards are similar in concept as to labeling the weight of an item (drug, excipient etc.) with a weighing-scale associated with it – which obviously would be unacceptable.

The concept of product-independent product evaluation would not only be scientifically valid but would also facilitate simpler and expeditious product evaluation and approval.

Therefore, the concept of product dependent assessment of products requires reconsideration. I hope this suggestion will be given a favorable consideration.

Future of regulatory pharmaceutical science: What to expect – a collapse!

In my view, collapse of the regulatory pharmaceutical science as we know it is coming because it is reaching the limits of promoting fake-science, regulatory bullying and disregard of consumer/patient needs and affordability.

To begin with, it is not even possible to know what one means by the regulatory pharmaceutical science or regulatory science. In simple terms it may be considered as a hodgepodge collection of documents and check lists often termed as Regulatory Guidance/Guidelines or pharmacopeial monographs, compiled by like-minded groups of people to impose their views as to how pharmaceutical products should be manufactured and/or evaluated. The main promoted objective of such exercises is to provide “care or help” to customers/patients by establishing “quality” of pharmaceutical products, such as tablet/capsule, which should be available at reasonable prices. The irony is that there is no definition or criterion provided for evaluating quality of products. The regulatory authorities and pharmaceutical community in general never defined what a quality pharmaceutical product is. Compliance to guidances is considered to reflect quality without an established link between the two (compliance and quality). Thus, everything related becomes illusionary and scientifically invalid requiring extra ordinary efforts, mostly bullying, to promote and maintain the pretense of patients’ safety and product quality

There is, thus, an urgent need for reassessing current regulatory practices so that manufacturing of pharmaceutical products and their assessments start to make sense and consumers/patients have access to affordable quality pharmaceutical products. Some ideas and suggestions, as links to some articles, are provided in this regard.

Issues:

(1)    Defining roles and practices of pharmaceutical regulatory authorities (http://www.drug-dissolution-testing.com/?p=2919)

(2)    In-compliance with regulatory standards and requirements do not necessarily mean that a pharmaceutical product (tablet/capsule) or process is of quality! (http://www.drug-dissolution-testing.com/?p=2389 )

(3)    In all seriousness – this is really an “abracadabra” exercise! (http://www.drug-dissolution-testing.com/?p=2914).

(4)    Quality assessment and prevailing illusions! (http://www.drug-dissolution-testing.com/?p=2741)

(5)    KABOOM! Pharmaceutical Product Quality Issue (http://www.drug-dissolution-testing.com/?p=2822)

(6)    Something to think about! (http://www.drug-dissolution-testing.com/?p=2814).

(7)    Bio-waivers! (http://www.drug-dissolution-testing.com/?p=2761)

(8)    Inspections and quality of pharmaceutical products and/or manufacturing processes – dilemma! (http://www.drug-dissolution-testing.com/?p=2722)

(9)    Fashionable Nonsense (http://www.drug-dissolution-testing.com/?p=2709)

(10)Non-GMP compliant dissolution testers but no warning letters! (http://www.drug-dissolution-testing.com/?p=2668)

(11)A Quality Product – Please Define! (http://www.drug-dissolution-testing.com/?p=2647).

(12)Let me be bold and direct! (http://www.drug-dissolution-testing.com/?p=2640)

(13)Assessing quality of pharmaceutical products! (http://www.drug-dissolution-testing.com/?p=2623).

(14)Scientific and GMP violation! (http://www.drug-dissolution-testing.com/?p=2608)

(15) Guidance Documents – Deficiency (http://www.drug-dissolution-testing.com/?p=2601 )

(16)f2 – Similarity Factor (http://www.drug-dissolution-testing.com/?p=2595)

(17)If one likes that a manufactured drug product should be of quality, then one needs to define (tell) what a quality product is? (http://www.drug-dissolution-testing.com/?p=2399).

Suggested Solutions:

(1)    Quality of Pharmaceutical Products (http://www.drug-dissolution-testing.com/?p=2644)

(2)    The missing quality definition or metric (http://www.drug-dissolution-testing.com/?p=2521)

(3)    Product Quality Metric (do not confuse it with drug/medicine quality) (http://www.drug-dissolution-testing.com/?p=2655)

(4)    Universal Dissolution Test/Tester (http://www.drug-dissolution-testing.com/?p=2364)

(5)    Universal Dissolution Test/Tester – Second Part (http://www.drug-dissolution-testing.com/?p=2369)

(6)    Promoting quality standards for drug products: Scientifically speaking, please be systematic and logical! (http://www.drug-dissolution-testing.com/?p=2359)

(7)    Establishing safety, efficacy and quality of drugs and drug-products (tablet/capsule) – serious confusion! (http://www.drug-dissolution-testing.com/?p=2351)

Defining roles and practices of pharmaceutical regulatory authorities

There is no doubt that regulatory authorities worldwide are facing numerous challenges in establishing efficient availability of quality pharmaceutical products, in particular tablet and capsule. It appears that a lack of clarity of objective/mandate may be the main cause of the problem, and by extension the reason there are difficulties in addressing these. The following suggestions maybe considered in addressing the current challenges.

  1. If the objective is to facilitate bringing quality products to patients, which indeed is the objective, then authorities should establish a definition of the “quality products” providing a reference quality product with associated measureable quality parameter. In the absence of a definition, it is impossible for anyone to manufacture and/or evaluate a quality product. A suggested definition in this respect is provided here.
  2. On the other hand, if the objective is monitoring the quality of the manufacturing, which appears to be the main emphasis of current regulatory practices (cGMP etc.). Then, authorities should not be in this business because this is neither their mandate nor do they possess competency/expertise in the area. They have never developed or manufactured products or run or maintain cGMP manufacturing facilities for commercial purposes. It would, therefore, be impossible to evaluate or guide the industry adequately to establish or run efficient manufacturing facilities.

Hope these suggestions would be given favorable consideration.

In all seriousness – this is really an “abracadabra” exercise!

Otherwise how else one should as a scientist differentiate the products in the two bottles when differences are not defined or measurable (1).

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