Cambodia's Ministry of Health and the Department of Drugs and Food have been actively working to reduce the amount of poor quality medicines circulating in the pharmaceutical sector since fake mefloquine and artesunate were first found in 1998. From 2005-2012, legal private sector facilities and illegal outlets in twelve Cambodian provinces were targeted for routine surveillance of medicine quality through sample collection and testing of various anti-infective medicines, the majority of which were anti-malarials and anti-biotics. The Medicine Quality Monitoring program samples from the field were analyzed through a three level approach including field and advanced laboratory testing. 4,381 medicines were collected and tested from 2005-2012; 106 have failed quality testing resulting in an overall failure rate of 2.4%. 28 of the failed samples (26.4%) were counterfeit. The most commonly found counterfeit medicines were chloroquine, artesunate, mefloquine, ampicillin and penicillin. Cambodia has closed over 99% of illegal pharmacy outlets through the Inter-Ministerial Committee to Fight against Counterfeit & Substandard Medicines (IMC) by the end of November 2011. In the past, a lack of resources as well as coordination among the various ministries was identified as a major barrier in combating the presence of poor quality medicines. With financial support from USAID, PMI, and other donors, paired with the technical support from the U.S. Pharmacopeial Convention Promoting the Quality of Medicines program, the IMC developed an action plan to significantly reduce the number of substandard and counterfeit medicines. Based on the data shown, the plan has been successful in reducing the failure rates of samples collected in Cambodia from a high of 7.4% in 2006 to a low of 0.7% in 2011. Continued efforts to monitor and actively ensure the quality of medicines in Cambodia will be required to maintain these low rates; sustainability of these efforts is critical.
The prevalence, availability, and use of antimalarial medicines (AMLs) were studied in six Cambodian provinces along the Thai-Cambodian border. The study was divided into two parts: the first looked at the quality of AMLs available in Pursat, Pailin, Battambang, Bantey Meanchey, Oddar Meanchey, and Preah Vihear and the second obtained information about the availability and use of AMLs. A randomized sampling methodology was used to select locations and collect samples, which were screened using Global Pharma Health Fund (GPHF) Minilabs. A subset of samples was sent to quality control laboratories for confirmatory testing. For the second part of the study, face-to-face interviews were conducted using standardized surveys with members of randomly selected households and staff of health facilities in the villages with highest malaria incidence to find out where they acquired their AMLs and which were most frequently used. The results showed an overall failure rate of 12.3% (n = 46 of 374 total AML samples). The causes of medication sample failure were low active pharmaceutical ingredient (API) content, failed dissolution properties, and unacceptably high levels of impurities. A total of 86.2% of survey respondents (n = 1,648 of 1,912) reported a member of their household having malaria in the previous year. The most commonly used medicines were paracetamol (67.1% of respondents), Malarine (A+M co-blistered, 28.6%), artesunate + mefloquine co-blistered (public sector product, 17.3%), quinine (16.7%), and artesunate monotherapy (11.9%). Health staff typically prescribed co-blistered artesunate plus mefloquine in the public sector (67.8%), the artesunate plus mefloquine "social marketing" product from Population Services International (PSI), Malarine (50.3%) in the private sector, artemether (49.7%), chloroquine (39%) and paracetamol (72.9%) to reduce fever.
Journal»The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
SETTING: Pharmacies in 19 cities in Angola, Brazil, China, Democratic Republic of Congo, Egypt, Ethiopia, Ghana, India (n = 3), Kenya, Nigeria, Russia, Rwanda, Thailand, Turkey, Uganda, United Republic of Tanzania and Zambia.
OBJECTIVE: To assess the quality of the two main first-line anti-tuberculosis medicines, isoniazid and rifampicin, procured from private-sector pharmacies, to determine if substandard and falsified medicines are available and if they potentially contribute to drug resistance in cities in low- and middle-income countries.
DESIGN: Local nationals procured 713 treatment packs from a selection of pharmacies in 19 cities. These samples were tested for quality using 1) thin-layer chromatography to analyze levels of active pharmaceutical ingredient (API), and 2) disintegration testing.
RESULTS: Of 713 samples tested, 9.1% failed basic quality testing for requisite levels of API or disintegration. The failure rate was 16.6% in Africa, 10.1% in India, and 3.9% in other middle-income countries.
CONCLUSIONS: Substandard and falsified drugs are readily available in the private marketplace and probably contribute to anti-tuberculosis drug resistance in low- and middle-income countries. This issue warrants further investigation through large-scale studies of drug quality in all markets.
BACKGROUND: Ensuring the quality of malaria medicines is crucial in working toward malaria control and eventual elimination. Unlike other validated tests that can assess all critical quality attributes, which is the standard for determining the quality of medicines, basic tests are significantly less expensive, faster, and require less skilled labour; yet, these tests provide reproducible data and information on several critical quality attributes, such as identity, purity, content, and disintegration. Visual and physical inspection also provides valuable information about the manufacturing and the labelling of medicines, and in many cases this inspection is sufficient to detect counterfeit medicines. The Promoting the Quality of Medicines (PQM) programme has provided technical assistance to Amazon Malaria Initiative (AMI) countries to implement the use of basic tests as a key screening mechanism to assess the quality of malaria medicines available to patients in decentralized regions.
METHODS: Trained personnel from the National Malaria Control Programmes (NMCPs), often in collaboration with country's Official Medicine Control Laboratory (OMCL), developed country- specific protocols that encompassed sampling methods, sample analysis, and data reporting. Sampling sites were selected based on malaria burden, accessibility, and geographical location. Convenience sampling was performed and countries were recommended to store the sampled medicines under conditions that did not compromise their quality. Basic analytical tests, such as disintegration and thin layer chromatography (TLC), were performed utilizing a portable mini-laboratory.
RESULTS: Results were originally presented at regional meetings in a non-standardized format that lacked relevant medicines information. However, since 2008 information has been submitted utilizing a template specifically developed by PQM for that purpose. From 2005 to 2010, the quality of 1,663 malaria medicines from seven AMI countries was evaluated, mostly collected from the public sector, 1,445/1,663 (86.9%). Results indicate that 193/1,663 (11.6%) were found not to meet quality specifications. Most failures were reported during visual and physical inspection, 142/1663 (8.5%), and most of these were due to expired medicines, 118/142 (83.1%). Samples failing TLC accounted for 27/1,663 (1.6%) and those failing disintegration accounted for 24/1,663 (1.4%). Medicines quality failures decreased significantly during the last two years.
CONCLUSIONS: Basic tests revealed that the quality of medicines in the public sector improved over the years, since the implementation of this type of quality monitoring programme in 2005. However, the lack of consistent confirmatory tests in the quality control (QC) laboratory, utilizing methods that can also evaluate additional quality attributes, could still mask quality issues. In the future, AMI countries should improve coordination with their health authorities and their QC lab consistently, to provide a more complete picture of malaria medicines quality and support the implementation of corrective actions. Facilities in the private and informal sectors also should be included when these sectors constitute an important source of medicines used by malaria patients.
BACKGROUND: Despite a significant reduction in the number of malaria cases in Guyana and Suriname, this disease remains a major problem in the interior of both countries, especially in areas with gold mining and logging operations, where malaria is endemic. National malaria control programmes in these countries provide treatment to patients with medicines that are procured and distributed through regulated processes in the public sector. However, availability to medicines in licensed facilities (private sector) and unlicensed facilities (informal sector) is common, posing the risk of access to and use of non-recommended treatments and/or poor quality products.
METHODS: To assess the quality of circulating anti-malarial medicines, samples were purchased in the private and informal sectors of Guyana and Suriname in 2009. The sampling sites were selected based on epidemiological data and/or distance from health facilities. Samples were analysed for identity, content, dissolution or disintegration, impurities, and uniformity of dosage units or weight variation according to manufacturer, pharmacopeial, or other validated method.
RESULTS: Quality issues were observed in 45 of 77 (58%) anti-malarial medicines sampled in Guyana of which 30 failed visual & physical inspection and 18 failed quality control tests. The proportion of monotherapy and ACT medicines failing quality control tests was 43% (13/30) and 11% (5/47) respectively. A higher proportion of medicines sampled from the private sector 34% (11/32) failed quality control tests versus 16% (7/45) in the informal sector. In Suriname, 58 medicines were sampled, of which 50 (86%) were Artecom®, the fixed-dose combination of piperaquine-dihydroartemisinin-trimethoprim co-blistered with a primaquine phosphate tablet. All Artecom samples were found to lack a label claim for primaquine, thus failing visual and physical inspection.
CONCLUSIONS: The findings of the studies in both countries point to significant problems with the quality of anti-malarial medicines available in private and informal sector facilities as well as the availability of therapy not compliant with national treatment guidelines. They also stress the need to strengthen regulatory control efforts on the availability of anti-malarial medicines in these sectors and in endemic areas.
Most donor agencies only procure drugs approved by a Stringent Regulatory Authority or the World Health Organization (WHO) Prequalification Programme in an effort to ensure high quality. This study compares the quality of artemisinin-based combination therapies (ACTs) produced by WHO-approved manufacturers with non-approved manufacturers and suggests policy changes to improve quality of donor-procured drugs. The results of this study suggest that ACTs produced by WHO-approved manufacturers perform nearly five times better than those of non-approved manufacturers, but some approved ACTs have too little active pharmaceutical ingredient. The US President’s Malaria Initiative tests every batch of every drug it procures before distribution to recipient countries. Other donors should follow suit to ensure that drugs purchased with taxpayer dollars are of the highest quality.
Focusing on 8 drug types on the WHO-approved medicine list, we constructed an original dataset of 899 drug samples from 17 low- and median-income countries and tested them for visual appearance, disintegration, and analyzed their ingredients by chromatography and spectrometry. Fifteen percent of the samples fail at least one test and can be considered substandard. After controlling for local factors, we find that failing drugs are priced 13.6-18.7% lower than non-failing drugs but the signaling effect of price is far from complete, especially for non-innovator brands. The look of the pharmacy, as assessed by our covert shoppers, is weakly correlated with the results of quality tests. These findings suggest that consumers are likely to suspect low quality from market price, non-innovator brand and the look of the pharmacy, but none of these signals can perfectly identify substandard and counterfeit drugs.
Report»Quality Assurance and Safety: Medicines, Essential Medicines and Pharmaceutical Policies Health Technologies and Pharmaceuticals, WHO Regional Office for Europe
EXECUTIVE SUMMARY: 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. A total of 291 samples of medicines 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 value, sterility, and bacterial endotoxins. No sample was suspected to be of a spurious, falsely-labelled, falsified or counterfeit product. 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. Of 42 isoniazid/rifampicin FDC samples collected, 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), 25 of which were of WHO-prequalified products. 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. For the purpose of differentiating between deviations which are likely to impact the health of patients and those which are not, the category of extreme deviations was arbitrarily defined as the content of API deviating by more than 20% from the declared content and/or average dissolution value of tested units below pharmacopoeia Q value minus 25%.Focusing only on extreme deviations from specifications, the total failure rate reached 1.0%. 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. 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 on further steps to improve the situation are listed in Box 1. (PDF)
Nigeria is one of the few countries seriously affected by counterfeit drugs to have actively combated them. As part of this effort its regulatory agency, NAFDAC, has deployed handheld spectrometers to identify fake drugs in the market. In this Outlook, we analyze anti-malarial drug samples procured randomly from pharmacies in the largest city in Nigeria, the port of Lagos prior to and after the spectrometers were deployed. There is a statistically significant drop in the number of drugs failing quality control tests after the spectrometers were introduced, and a noticeable disparity in price between those passing and those failing tests as well. While it is not likely that the deployment of the spectrometers is the only reason for the improvement in drug quality, and the segmentation of the market, it is surely a major factor.
Cambodia's Ministry of Health and the Department of Drugs and Food have been actively working to reduce the amount of poor quality medicines circulating in the pharmaceutical sector since fake mefloquine and artesunate were first found in 1998. From 2005-2012, legal private sector facilities and illegal outlets in twelve Cambodian provinces were targeted for routine surveillance of medicine quality through sample collection and testing of various anti-infective medicines, the majority of which were anti-malarials and anti-biotics. The Medicine Quality Monitoring program samples from the field were analyzed through a three level approach including field and advanced laboratory testing. 4,381 medicines were collected and tested from 2005-2012; 106 have failed quality testing resulting in an overall failure rate of 2.4%. 28 of the failed samples (26.4%) were counterfeit. The most commonly found counterfeit medicines were chloroquine, artesunate, mefloquine, ampicillin and penicillin. Cambodia has closed over 99% of illegal pharmacy outlets through the Inter-Ministerial Committee to Fight against Counterfeit & Substandard Medicines (IMC) by the end of November 2011. In the past, a lack of resources as well as coordination among the various ministries was identified as a major barrier in combating the presence of poor quality medicines. With financial support from USAID, PMI, and other donors, paired with the technical support from the U.S. Pharmacopeial Convention Promoting the Quality of Medicines program, the IMC developed an action plan to significantly reduce the number of substandard and counterfeit medicines. Based on the data shown, the plan has been successful in reducing the failure rates of samples collected in Cambodia from a high of 7.4% in 2006 to a low of 0.7% in 2011. Continued efforts to monitor and actively ensure the quality of medicines in Cambodia will be required to maintain these low rates; sustainability of these efforts is critical.
