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Consumers and patients must wait, and suffer, for the availability of quality pharmaceutical products such as tablet/capsule as well as their genuine and affordable prices. The reason may surprise you!

It is important to note that at present availability of the pharmaceutical products such as tablet and capsule is heavily regulated, more accurately controlled, by the regulatory authorities worldwide. Manufacturers and suppliers have to follow extensive suites of protocols (national and/or international) to get their products approved for marketing. These protocols are often described by different names such as regulations, guidelines, standards etc. The manufacturers have to be in compliance with these protocols literally to the letter, which are mostly arbitrary in nature. Thus, in practical terms contrary to popular belief, there is limited or no room for deviation, simplification and/or innovation from these protocols at least from the manufacturers’ side.
In simple terms, these protocols may be considered as formats for data/results presentations, may these be for the product development or manufacturing – promoted as regulatory science. However, unfortunately, these are administrative and procedural requirements, not the practice and/or requirement of the science. The underlying “science” remains based on traditional practices and assumptions, more accurately may be considered as rituals. Therefore, with the passage of time and the introduction of extensive sets of standards and requirements, the burden of adhering to these regulatory formats (“guidelines”) has become increasingly frustrating, time consuming and financially challenging for the both, authorities and the manufacturers, without any added value to the product quality and/or benefit to the users.
In addressing these challenges, manufacturer bashing approaches (implied or explicit) are common and fashionable, often criticizing lack of their integrity and competencies. This approach certainly appears to be a deviation away from the regulatory mandate or requirements which is establishing and monitoring quality of the products and not that of assessing and criticizing manufacturing ability or capacity. Regulators’ and their associates should be able to establish if the manufactured products, at the consuming stage, are of the required quality, and by extension, safe and efficacious. However, they can’t at present – thus deviation from their mandated objective!
There are two reasons for this regulatory shortcoming: (1) Regulatory authorities have never defined required quality, and its associated parameter, for the product assessments. In fact, it could be argued that it is unknown to them. (2) Authorities require and enforce a large array of flawed product testing requirements for compliance purposes without their validations and relevance. As these requirements lack scientific credibility and validity, anybody, not just the manufacturers, would have difficulty in meeting or will be unable to meet the current regulatory requirements and expectations. For a more technical description of this aspect please consider viewing the links provided below.
Therefore, there is a clear need for re-evaluating the practice of setting regulatory standards and requirements starting with the definition of a quality product followed by the use of scientifically/GMP valid instruments and procedures. Otherwise, it is impossible for the manufacturers to produce quality products, and for the regulators developing and implementing appropriate guidelines and standards for product evaluation.

Some suggestions are provided to address these issues, and it is sincerely hoped that authorities will give consideration to these thoughts.

For further reading:

Are bioequivalence (BE) assessments of clinical significance and relevance? Not really!

A discussion is provided showing weakness of BE assessments for comparing or establishing quality of products such as tablet/capsule. It is argued that in vitro drug dissolution/release testing would provide a better alternative for the assessment of the quality of such pharmaceutical products. Please click here for complete article.

Regulatory compliance is more appropriate description than QC/QA

It is important to note that at present pharmaceutical laboratories are operating under non-GLP/GMP conditions, in particular for the assessment of solid oral dosage forms such as tablet and capsule products. This is surprising that such negligence has been going on unchecked. This deficiency needs to be corrected so that facilities can be considered as QC/QA laboratories to provide relevant and accurate quality characteristics of the products. For further details, please follow the links (1, 2, 3).

Need for a quantifiable quality parameter for pharmaceutical (tablet/capsule) products

People try to understand the logic and scientific principles behind the (pharmacopeial and regulatory) “compliance” requirements for meeting the quality aspect of the pharmaceutical products such as tablet/capsule. However, there is hardly any scientific principle involved in most of the current “compliance” requirements in the area. Most compliance requirements are based on subjective (individual or collective) opinions and guesses, often presented through publications or regulatory guidance documents to gain or establish their authenticity. For example, in the area of establishing quality of the manufactured products, such as tablet/capsule of both generic and branded products, nowhere it is defined what would be considered as a “quality product” and how the quality should be measured or established. However, all the pharmacopeial and regulatory requirements (national or international) make claims of achieving it. Is it not interesting that quality of a product is not defined or known, but claimed to be achieved, how?

Quality assessment of pharmaceutical products – regulatory/pharmacopeial standards and methods require urgent attention!

A patient needs a drug but prescribed or purchases a drug product (such as tablet or capsule) with an implied assurance that product will release the drug in the body as expected to provide its therapeutic effect. This characteristic of drug release/delivery in the body from the product defines the quality of the product.

At the manufacturing stage one hardly ever conducts clinical tests to establish the safety and efficacy of the products but only the “quality” tests. The reason being if the quality is acceptable then safety and efficacy will be acceptable as well because drug levels in the body and safety and efficacy are directly linked.

The tests most often conducted to establish quality of products at the manufacturing stage are the chemical tests, commonly known as in vitro tests. The most common in vitro test which is conducted to establish drug release or quality of the tablet/capsule products is known as a drug dissolution test. This is the only test which forms the basis of quality assessment of tablet/capsule products. Regulatory authorities, including pharmacopeias, worldwide recommend and enforce proper use of this test to establish the quality of the products. There are numerous guidance documents available from the regulatory authorities, including US FDA, which describe the requirements of the dissolution testing procedures forming the basis of drug product approvals.

The important, and perhaps a very disturbing, fact to note here is that the dissolution testers, along with associated methods, as recommended by the authorities have never been validated for their intended use or relevance. In fact, many scientific studies (e.g. link) have clearly shown that the tests do not and cannot provide relevant results i.e. the testers cannot provide accurate results/data regarding the products (tablet/capsule) quality. Therefore, any claims made regarding the quality of the approved products by anyone, including authorities, lack accuracy and scientific authenticity.

The regulatory authorities enforce extensive set of requirements and standards through elaborated set of “compliance” guideline such as ICH or US FDA guidance documents for establishing quality of the products. This guidance-based compliance system is directly or indirectly dependent on the drug dissolution test at least for tablet/capsule products. Therefore current guidance-based system is not only providing false assurance about the quality of the products but also causing severe hindrance for the industry to produce quality products appropriately and efficiently. In addition, this guidance based system adds enormous administrative burden for both, authorities and manufacturers – unfortunately of no or limited benefit to either party. Furthermore, as the recommended testers are non-qualified/non-validated which makes them non-GMP compliant, thus authorities could easily be found in violation of GMP practices – potentially a serious and disturbing claim. Therefore, this deficiency should be addressed on an urgent basis with the highest priority.

It is important to note that scientific studies have clearly shown that currently recommended apparatuses have a design problem which could be corrected by simple modification. Suggestions have been made in the literature in this respect addressing the issues. Further information in this regard may be obtained from here.

In short, authorities should take a note of this critical deficiency which exists in the drug product approval requirements caused by requiring non-GMP drug dissolution testers. This deficiency needs to be addressed quickly so that quality of the manufactured products could be established and monitored accurately and efficiently.

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