Substandard medicines are becoming a global concern that is particularly endemic in developing countries. According to the WHO Substandard medicines are genuine drugs produced by legitimate manufacturers which do not meet the recognized quality and purity standards. A substandard drug is a medicine that does not meet specifications necessary to ensure quality, efficacy and safety; has not demonstrated bioequivalence to the originator; or does not have sufficient evidence to demonstrate originator data can be referenced. In general the substandard drugs are copies of medicines that have been approved in countries with limited regulatory standards and thus might not be made to high quality standards or be sufficiently tested to be approved in countries with more stringent regulatory standards and controls, eg, US, EU, Japan, and Australia. The synthesis of pharmaceutical products frequently involves the use of reactive reagents and the formation of intermediates and by-products. Low levels of some of these may be present in the final drug substance and/or drug product as impurities resulting either from the synthesis process or from degradation. Such chemically reactive impurities may have the potential for unwanted toxicities including genotoxicity and carcinogenicity. So, besides not providing any benefit to patients they may, if not tightly controlled, be hazardous. The pharmaceutical industry and the regulatory agencies (e.g. US-FDA, EMA) recognize their respective obligation to limit specifically genotoxic impurities. Therefore, substantial efforts are made during development to control all impurities at safe concentrations. Control of impurities in the drug substance and degradants in drug product are addressed in the respective ICH Quality Guidelines. Justification of limits per these ICH guidelines is normally based on the qualification of batches of the active pharmaceutical ingredient including its impurities in pivotal toxicity studies that include genetic toxicology tests. According to current regulatory practice it is assumed that genotoxic compounds with a direct interaction with DNA have the potential to damage DNA at any level of exposure and that such damage may lead/contribute to tumor development. Therefore the use of poor quality and potentially harmful substandard medicines especially with high levels of genotoxic impurities could lead to therapeutic failure, exacerbation of disease, resistance to medicines and sometimes death.


Article metrics loading...

Loading full text...

Full text loading...

  • Received: 12 May 2012
  • Accepted: 12 May 2012
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error