[This post results from a query to one of my posts on LinkedIn Network (link), I think visitors of my website would also find it a useful read]

I believe your view/confusion is valid and understandable considering the current state of drug product evaluation practices. Note that this confusion occurs from considering or mixing drugs and drug products as the same. You are not alone with this confusion; even the regulatory authorities are confused with it, in fact indirectly extending it. For example, for generic product evaluations US FDA requires ANDA (abbreviated new DRUG application, in Canada ANDS), which is an incorrect terminology and in reality these are new PRODUCT applications (link). Your confusion also appears to be arising from the same mix-up i.e., not differentiating the drugs from drug products.

My post is regarding PRODUCTs, where one hardly ever conducts clinical tests/studies especially at the commercial production stage. Safety and efficacy studies/evaluations of DRUGS are done in the beginning, sometimes decades ago (e.g., consider the examples of aspirin, acetaminophen, ibuprofen, and others perhaps most drugs). From these clinical studies dose levels are set based on their safety and efficacy profiles.

At the production stage these drugs as PRODUCTS are manufactured worldwide without any further clinical evaluation. At the production/manufacturing stage objective is to produce PRODUCTs of the drugs which must contain the required dose and they must also be capable of providing (often described with terminologies of releasing/delivering/bioavailability) expected amount of the drug in the human body whichever route of drug administration is suggested (often time it is oral, but could be others IV, dermal, sublingual etc.). There would not be any concern or focus here for the safety and efficacy of the drug, along with other non-actives or excipients, which have been already established. In the generics cases, these are assessed often by bioavailability or bioequivalence assessments which is also usually one time shot and often at the pre-production stage. The point being that at the production stage there is hardly any (clinical) safety and efficacy assessment.

On the other hand, at the production stage safety and efficacy refer only to the ability of the product to release drug/dose as expected and this becomes quality metric for the product. If a product does not deliver/release the drug/dose as expected it would not be of quality which mean (equal to) it would not be efficacious and/or safe. This is where equality comes from (you may consider it as mathematical relationship if you like which may not be incorrect either), however, we are dealing with yes/no, pass/fail, or equal/not-equal situation.

So, in short, at the production stage of the PRODUCTs, quality is equal to safety and efficacy.

Safety and efficacy of the pharmaceutical products (e.g. tablet/capsule) can only be established by determining quality of the products. If quality of the products cannot be established, as currently is the case, then claims of safety and efficacy cannot be made either. In addition, as compliance does not necessarily equate quality, safety and efficacy cannot be achieved by compliance as well. Use caution in promoting or accepting such claims. Quality of the products, and by extension their safety and efficacy, has to be defined and determined independently.

Please seek definition of the quality of the pharmaceutical products in terms of a quantifiable parameter to substantiate claims of safety and efficacy. For further details the following links would be useful (1, 2, 3) .

It is really hard to believe or accept how people have been blind-sided with “validation” (re-validation, continued validation etc.) requirement. The simple fact is that to run validation for any process one requires a reference product or parameter to show that process is validated (or capable of providing an expected outcome or product). If one does not have a reference product with known parameter and its value, then it is impossible to validate anything. Please, people this is logic and science 101.

If anyone is requiring or conducting validation without a reference (as in the case of current practices of manufacturing of quality pharmaceutical products in particular tablet/capsule), then validation of such manufacturing processes must be considered as “abracadabra” practices commonly accepted as meeting the “compliance”, “harmonized standard” etc. and do not link to quality aspect of the process or product.

I hope authorities, including pharmacopeias, will work in addressing these bizarre trends of validation approaches/concepts currently in practice and/or required, which have no scientific and/or logical basis.

Please, define a quality product and then provide a reference product which would allow the manufacturers to meet or exceed the standards of quality.