Survey of the quality of anti-tuberculosis medicines circulating in selected newly independent states of the former Soviet Union
The aim of this survey was to explore the quality of anti-tuberculosis medicines in use in selected newly independent states of the former Soviet Union (NIS), as one of the potential factors contributing to the high burden of multidrug-resistant tuberculosis (MDR-TB) observed in all of these countries.
Samples of selected first and second-line anti-TB medicines were collected from public and private sector procurement and treatment centres in Armenia, Azerbaijan, Belarus, Kazakhstan, Ukraine, and Uzbekistan. 291 samples containing rifampicin, isoniazid, kanamycin or ofloxacin produced by 33 manufacturers were collected from 84 collection sites. Samples were tested by preselected reliable laboratories for appearance, identity, assay (content of active ingredient), related substances, dissolution and uniformity of mass. Injections, solutions, and powders for injection were also tested for pH, sterility, and bacterial endotoxins.
No falsely-labelled, falsified or counterfeit products were found. There were no quality problems identified with samples of kanamycin powder for solution for injection, isoniazid solution for injections or ofloxacin solution for infusion. Isoniazid/rifampicin FDC was the only medicine of which WHO-prequalified samples were collected in this survey and of 42 such preparations, 38 were of prequalified products and none of those failed to comply with pre-set specifications. Neither did any of the 42 samples supplied through the Global Drug Facility(GDF).
Overall 33 samples (11.3%) failed to meet the specifications set for the survey. The highest failure rate was found for mono-component products containing rifampicin - more than a quarter of rifampicin samples (28.3%) failed to meet the specifications, and the predominant reason for this was that the content of active ingredient was below the acceptable limit. However, only 1% of samples were found to be so deficient as to present a risk to patients.
This seems to reflect relatively good overall compliance with quality standards, and the zero failure rate among WHO-prequalified samples and those supplied through GDF indicates that these mechanisms are effective in assuring the quality of anti-TB medicines. On the other hand, low content of rifampicin, substantial inconsistencies in ofloxacin dissolution, as well as batch-to-batch and intra-batch inconsistencies are of concern and need to be addressed. Furthermore, the bioavailability of rifampicin is well known to be a potential problem, but was beyond the capacity of this study.
These findings may be caused by a combination of inconsistent application of Good Manufacturing Practices (GMP) and insufficient regulatory supervision. An impact of inappropriate distribution and storage conditions could not be excluded, but there was not
enough information to relate the quality problems identified to specific distribution or storage problems.
The results of the survey cannot be generalized to the overall anti-TB medicines market in the surveyed countries because of limitations in the sampling, and - although they are encouraging - they indicate that further efforts are required to facilitate access to medicines that meet international quality standards in order to ensure the provision of quality anti-TB medicines to patients in the region. The results of the survey were analysed with representatives of participating countries, and agreed recommendations included:
Ministries of health to:
- Promote the use of quality-assured FDCs, and avoid the use of mono-component rifampicin;
- To advocate for the participation of manufacturers in the WHO Prequalification of Medicines Programme;
- To continue working with national medicines regulatory authorities (NMRAs) to improve regulatory systems at country level
WHO and National Medicines Regulatory Authorities to:
- Investigate reasons for use of injectable forms of isoniazid, ofloxacin and other anti-TB medicines;
- To support resource mobilization for strengthening of medicines regulatory systems.