[e-drug] Identification of substandard and falsified medicines: Influence of different tolerance limits and use of authenticity inquiries

e-drug
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E-DRUG: Identification of substandard and falsified medicines: Influence of different tolerance limits and use of authenticity inquiries
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Dear e-druggers,

I am happy to share with you the recently published article

'Identification of substandard and falsified medicines: Influence of
different tolerance limits and use of authenticity inquiries' by our
group at the Pharmaceutical Institute of Tuebingen University.

With this article we hope to contribute to an improvement of the
comparability of future studies on the prevalence of substandard and
falsified medicines. Using the assay results of 601 medicine samples
which we had collected in Cameroon, DR Congo and Malawi, we show that
the rate of 'out-of-specification'(OOS) medicines can range from 3.3%
up to 35.0%, simply depending on the choice of tolerance limits used
in the evaluation of the data. For better harmonization, we therefore
suggest to use the tolerance limits of the International Pharmacopoeia
or of the United States Pharmacopeia in future studies.

Furthermore, we describe in detail an authenticity inquiry which we
carried out by contacting the stated manufacturers and distributors of
the aforementioned medicine samples. Three samples had been identified
as falsified by packaging analysis and chemical analysis, but notably
seven additional samples were identified as falsified by the
authenticity inquiry.

In this study we classified samples as 'in-specification' and
'out-of-specification' based on their analytical results. We further
used the current WHO definitions to classify samples as 'substandard'
(i.e. OOS medicines for which no evidence is available that they
deliberately/fraudulently misrepresent their identity, composition, or
source) or as 'falsified' (i.e. medicines that deliberately/fraudulently misrepresent their identity, composition, or source, irrespective of whether their analytical results are in specification or OOS).

Finally, we present suggestions which may contribute to a harmonization of studies on substandard and falsified medicines in future.

The online ahead of print article can be accessed using the following link:
https://doi.org/10.4269/ajtmh.20-1612

Kind regards,
Cathrin

Cathrin Hauk
Apothekerin, Doktorandin
Eberhard Karls Universitat Tuebingen
Pharmazeutische Biologie, Pharmazeutisches Institut
cathrin.hauk@uni-tuebingen.de

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E-DRUG: Identification of substandard and falsified medicines:Influence of different tolerance limits and use of authenticity inquiries (2)
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Dear Cathrin,
Thanks for sharing this interesting article which sheds light on a phenomenon that some of us have observed over the years in testing pharmaceutical products using different pharmacopeias. Essentially, the outcome of testing a medicine and making determination about whether the medicine is of good quality or not could depend on the pharmacopeia used to test that medicine. It coveys the unfortunate message that quality is not absolute but is relative. This is unsettling because you would think that quality is binary- that is, a medicine is either of good quality or it is not, independent of which pharmacopeia is used to test it.

By having different outcomes of product quality that is dependent on which pharmacopeia is used to test it, disingenuous manufacturers could (and some do) cherry pick the pharmacopeia to use to demonstrate good quality of their product. This is unacceptable and makes the case for the urgent harmonization of pharmacopeias.

But let's do a further introspection of how standards are set to show potential pitfalls that Pharmacopeias must address if they are not doing so already. Standards are set by characterizing an Active Pharmaceutical Ingredient (API) obtained through donation or in-house synthesis to establish its potency and impurity profile. The characterized material is packaged as a standard and can be used to test various dosage forms (tablets, capsules, liquids, etc) for their content, impurity profile, Identification, etc is as described in a given pharmacopeia monograph.

The reason why a given pharmaceutical product may be deemed as good quality by one pharmacopeia and not by another could be due to the following reasons:

1. If the pharmacopeia sets different tolerance limits on a given parameter such as ASSAY or RELATED SUBSTANCE, one can get a different outcome of product quality as clearly shown in the publication.
2. One pharmacopeia may request a certain test to establish product quality whilst another may not. For example, certain pharmacopeias require impurities test for a given dosage form whilst others do not because of the expected impurity burden from the synthetic scheme of the API used to make that product. If a different synthetic scheme is used by another manufacturer of that same product, and because monograph methods are not tied to synthetic schemes, the monograph method may no longer be adequate to control the impurities because they were not anticipated at the time of developing the monograph.

Based on these realities, the pharmacopeia used to test a certain product should be carefully thought through and pharmacopeia methods should be constantly updated to ensure that the current standards are still relevant and adequate to control the quality of products made using current schemes.

Patrick Lukulay, Ph.D.
President, Tech4Health
Accra, Ghana
"Dr. Patrick Lukulay" <phlukulay@gmail.com>