[e-drug] QAMSA Study on Substandard Antimalarials in Sub-Saharan Africa

E-DRUG: QAMSA Study on Substandard Antimalarials in Sub-Saharan Africa
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Dear E-Druggers:

Please see news released by USP/USAID on a new report on the quality of
antimalarial medicines in Sub-Saharan Africa.

Best regards,
Francine Pierson
USP

FOR IMMEDIATE RELEASE

CONTACT: Francine Pierson
301/816-8588; fp@usp.org

One-Third of Antimalarial Medicines Sampled in Three African Nations
Found to be Substandard in Large-Scale USP-WHO Study

Inadequacies May Contribute to Drug Resistance

Rockville, Md., February 8, 2010 — The first results from a large-scale
study of key antimalarial medicines in ten Sub-Saharan African countries
reveal that a high percentage of medicines circulating on national
markets are of substandard quality and thus may contribute to the growth
of drug-resistant strains of Plasmodium falciparum, the most virulent
form of malaria. The findings, released today by the Promoting the
Quality of Medicines (PQM) Program, a USAID-funded program implemented
by the U.S. Pharmacopeial Convention (USP), are for three countries
surveyed in the study—Madagascar, Senegal and Uganda.

The results are part of the larger Quality of Antimalarials in
Sub-Saharan Africa (QAMSA) study, a ten-country collaborative study
conducted by the World Health Organization (WHO) and PQM. Within
Madagascar, Senegal and Uganda, the study sampled 491 antimalarials,
performed basic testing on almost all, and submitted 197 samples to
full-scale quality control testing. The focus was on artemisinin-based
combination therapy (ACT) products, currently the WHO’s recommended form
of first-line treatment for uncomplicated malaria, and
sulfadoxine-pyrimethamine (SP) products, often used for preventative
treatment of malaria during pregnancy. The samples were collected from
the public and regulated private sectors in these countries, as well as
from informal markets, as many patients obtain their medicines from
these sources. Substandard and counterfeit versions of antimalarial
medicines are highly problematic throughout Africa, Asia and Latin
America because of the direct threat they pose to the lives of
individual patients as well as their contribution to the development of
drug-resistant strains of these diseases.

In total, the QAMSA study found that approximately 44 percent of sampled
medicines from Senegal, 30 percent of samples from Madagascar, and 26
percent of samples from Uganda that underwent full quality control
laboratory testing failed such testing and were thus substandard.
“Substandard” medicines are those that do not meet the quality
specifications set for them, primarily because they do not contain the
correct amount of the active ingredient(s), do not dissolve properly in
the body or include unacceptable levels of potentially harmful
impurities.

'The results of the study paint a very unfortunate picture of the
situation in Sub-Saharan Africa,'  said Anthony Boni, the Agreement
Officer's Technical Representative for the PQM Program, USAID Office of
Health, Infectious Diseases, and Nutrition. 'With almost half of
medicines in Senegal and more than one out of four medicines in
Madagascar and Uganda failing quality testing, clearly much work needs
to be done to provide patients with medicines that meet the level of
quality they require and deserve. These countries are committed to
protecting the health of their citizens, but the authorities face many
challenges in regulating their markets. We look forward to working
together with them to reduce the morbidity and mortality caused by
malaria, by improving the quality of the medicines used to treat this
disease.'

'Although alarming, this study offers extremely valuable information
that has already been shared with those countries in the hope that local
regulatory bodies will focus their attention on products, brands and
geographical locations where substandard medicines were found to pose
the biggest threats,' said Patrick Lukulay, Ph.D., Director of the PQM
Program at USP. 'The results show some significant differences in terms
of where the problems lie. These findings can be used immediately by
officials to target their efforts - an especially useful approach when
resources are scarce, as they are in these countries.'

The main purpose of the study was to update and expand the knowledge
base about the prevalence of substandard antimalarials in Sub-Saharan
Africa, which are believed to contribute to antimicrobial resistance of
Plasmodium falciparum. Already, Plasmodium falciparum has become
resistant to traditional monotherapy drugs such as chloroquine, and more
recently to SP products. The sustainability of treatment success depends
to a large extent on preventing Plasmodium falciparum's exposure to
incomplete doses of these medicines to minimize the possibility of the
emergence of drug resistance.

Beyond the overall failure rates, other noteworthy findings across the
three countries were that SP products were most likely to fail
dissolution tests (35 percent), while ACTs were most likely to fail
impurity tests (29 percent). No samples in the full study completely
lacked the active ingredient(s). The results also showed that, as a
general rule, when a brand passed or failed in one country, it would
also pass or fail in other countries. This indicates that the problem of
quality is created at the source, rather than during passage through the
distribution chain.

Despite some similarities, results by country varied in a number of
areas, including at which points of sale the substandard medicines were
found. In Madagascar, for instance, poor quality medicines appear to be
widespread across regions and not limited to any particular type of
distributor. In Uganda, samples fared much better in the public sector
than in the country's private sector. Despite overall failure rates,
this was one of the bright spots the study revealed; in Uganda's public
sector, all ACT and SP samples passed quality tests.

The report is believed to be unique in terms of the large numbers of
samples collected as well as the two-step testing approach employed in
the study, which included initial screening on site using Global Pharma
Health Fund portable Minilabs® and full-scale quality control
confirmatory testing of roughly 40 percent of the total samples at USP's
headquarters in the United States.

USAID is a U.S. government agency that provides economic, development
and humanitarian assistance around the world in support of the foreign
policy goals of the United States. USP is a nonprofit scientific
organization that sets globally recognized standards for the quality of
medicines. USP'™s work in developing countries to improve the quality of
medicines 'in large part by combating the availability of substandard and
counterfeit medicines intended to treat malaria, HIV/AIDS and
tuberculosis' is implemented under the PQM Program supported by USAID.

For more information, please email mediarelations@usp.org.

USP, USA
"Francine Pierson" <fp@usp.org>

E-DRUG: QAMSA Study on Substandard Antimalarials in Sub-Saharan Africa (2)
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Hi Francine,

Thanks for sharing this information. I am still awaiting to read the full report (just sent my request)... From the press release,- the results just confirm previous findings and reiterate 'the need for the involvement of' governments in implementing drug- quality programs in their countries'. For example how is it possible that all ACT medicines in the Ugandan public sector passed quality testing over those in the private sector (when it is the gov`t that is making the laws and overseeing its implementation)?

Throughout the press release there was no mention of the word `counterfeit` or `fake`. Is this an intentional omission or from all sampled none was found? At least the report should mention this as a compliment.

I am curious to know the type of impurities found in the ACT medicines since impurities in artemisinin compounds are yet to be fully elucidated in terms of identification and structure.

Kind regards.

Magnus Ajong Atemnkeng, PhD
Montreal, Canada
magnusajong@yahoo.com

E-DRUG: QAMSA Study on Substandard Antimalarials in Sub-Saharan Africa (3)
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Hi Magnus-

Thank you for your interest in the USP press release about the QAMSA study. Your questions are addressed in the full report which Francine will be sending to you. We would be happy to answer any additional questions you might have after reading the report. Regarding your question about the test results for the ACTs in the Ugandan public sector, the final confirmatory tests were conducted at a USP laboratory in the US, following well established compendial specifications. The Ugandan government had no oversight of the data and Ugandan statutes have no bearing on the interpretation of the data. (I hope I understood your question)

With respect to impurities in ACT, I disagree that the impurities in ACTs have not been characterized. In fact one of the major impurities in ACTs and a common cause for failure to meet quality specifications is the metabolite and degradation product known as Dihydroartemesinin (DHA) which is a sesquiterpene lactone (a derivative of artemesinin). In the report, any peak in the chromatogram which is not the main component and is not an excipient is referred to as "an impurity". These impurities when they occur over a certain threshold, constitute failure of the drug to meet quality specifications.

Hope this helps. Please feel free to engage after reading the full report.

Regards,

Patrick Lukulay, Ph.D.
Director, United States Pharmacopeia
Promoting the Quality of Medicines (PQM) program
PATRICK LUKULAY <plukulay@hotmail.com>