Professors from the UK, US, Belgium and Thailand said in the analysis piece that there are “many different types of poor quality drugs that could mistakenly be included in clinical trials, including those with no, too little, or too much active pharmaceutical ingredient [API], those with the wrong active pharmaceutical ingredient, those with inadequate bioavailability, and those that degrade with toxic products or contaminants.”
The authors use the example of a study from 2011 in which the antimalarial drug sulfadoxine-pyrimethamine in pregnant women in six countries in Africa was planned using four locally available brands. The products were tested at the US CDC and the sulfadoxine content of one of the brands was found to be below 90% of the manufacturer’s stated amount. An emergency request to procure a good quality brand was made and the study proceeded with confidence.
Similarly, in 2007, a consignment of clopidogrel labelled as Plavix worth £1m (€1.3m; $1.5m) for use as a comparator in a clinical trial in the US was found to be falsified. The trial was eventually able to proceed and the perpetrators were arrested.
But such studies may not always be so fortunate and the authors note that many countries, especially those in the developing world where many trials are conducted, have limited regulatory capacity for verifying bioequivalence.
“Drugs containing the same stated API are not necessarily bioequivalent if they are produced by different companies or in different batches. For example, different batches of mefloquine and digoxin tablets have shown non-bioequivalence. Thus, clinical trials using different brands or batches of the same drug may give different results, which makes interpretation difficult and can dilute the power of meta-analyses that underlie many policy recommendations,” the professors write.
The authors suggest that WHO and ICH guidelines on GCP be updated to include a requirement that states the quality of drugs and medical products, including diagnostic tests evaluated in trials or used for assessing inclusion criteria or endpoints. Batch numbers and expiry dates of drugs should also be included in trial reports and the manufacturers’ certificate of analysis should be published as supplementary material, the authors contend.