E-DRUG: Standard Substandard Falsified - sharing experiences
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[An informative and thought-provoking message which underlines how we are still struggling to deal with falsely-labeled/substandard/counterfeit/spurious medicines. What is possible in the short-term while we come up with longer-term measures? DB]
Dear Colleagues
*Standard /substandard / falsified – sharing experiences*
In the past a considerable number of e-drug readers participated in the
discussion about substandard and falsified medicines.
Difäm, (the German Institute for Medical Mission) works predominantly
with partners in Africa in the strengthening of church health work in
general and pharmaceutical supply systems in particular. We would like
to share some of our experience in assisting church-based drug supply
organizations (DSOs) to improve their quality control systems and/or to
support analyzing their products by using the WHO-prequalified lab of
the Mission for Essential Drug Supply (MEDS) in Nairobi/Kenya.
We are offering national drug supply organizations (DSOs) quality control
systems using a *pooled sampling/pooled testing arrangement*. Once or
twice per year DSOs provide up to five specific samples of commonly used
medicines to MEDS for USP-analysis. This pooling reduces the cost for
testing and gives a limited overview about the quality of specific
medicines used in participating countries. Starting in 2009 up to the
end of 2012 in total 17 DSOs and Difaem partners from 14 different
countries provided 234 samples of 27 different medicines/dosage forms
for testing.
Altogether 234 samples were manufactured by 108 different companies in
28 different countries. 56% of the samples were from Asia, 32% from
Africa, the rest from other continents.
76 samples had been manufactured in African countries according to label
information; 130 originated in Asia, all others from Europe and
elsewhere.Of all samples submitted 98 (42%) came from 40 different
companies in India; 33 (14%) from 6 companies in Kenya; 26 (11%) from 15
companies in China, only to name the main ones.
41 samples (17%) failed USP requirements - in turn this means that 83%
of all medicines that we tested are of good quality. The main problems
with substandard medicines were dissolution problems (17 of 41 samples)
Out of 41 samples that failed USP requirements 24 came from Asian
companies, 15 from Africa and 2 from Europe according to the label.
Beside this pooled sampling/testing Difaem is supporting its partners in
running a *Minilab* and is managing a “Minilab-Network” among them
including the possibility to confirm results by HPLC method used in
MEDS-lab in Kenya. [A f]ew falsified products and even a substandard
Amoxicillin (assay 81%) could initially be identified by using the
Minilab and confirmed afterwards.
*Challenges:*
1. How do we communicate with unknown companies?
Feedback is important. Companies have to know the results of testing,
especially if their product failed, but also if it passed. But how do we
communicate if the identity of manufacturer according to label is
insufficient and no physical address or e-mail can be found? We obtained
a quinine coated tablet from a partner in the Congo (DRC). According to
the label the medicine was manufactured by Lakeside in Amsterdam, a
company that does not exist to our knowledge. This product failed all
requirements and is therefore assumed a falsified one.
A database of all pharmaceutical companies with contact details and the
name/address of the QC manager would be a first step for better
information flow and quality control.
2. When are we talking about substandard?
When talking about substandard medicines which standard should be
applied? The term quality allows for variations. In one case a company
reported that the quality did not comply to USP standard - but they were
using BP instead of USP and BP is not that strong (i.e. for assay range
tolerated or medium used for dissolution test).
Medicine Procurement organizations buying directly from companies should
introduce and follow a SOP demanding that each and every offer not only
states a price but also refers to quality as well – ideally asking for
USP conformity.
In addition each product that is procured should come with a COA
(Certificate of Analysis) to be archived in good order. Only then it is
possible to compare the QC-statement of the manufacturer with the
results received by independent analyses executed by country regulatory
authorities (i.e. MoH), public or private qualified laboratories. This
will have to include wholesalers as well as international and
humanitarian aid organizations and apply to government tenders, etc.
3. What can we do if companies are ignoring updated test requirements?
What if a company ignores higher standards? A supplier producing Quinine
in the DRC was contacted because their samples failed present USP
standard. In their response they questioned the present USP standard and
replied that other companies also would not be able to achieve the
requirements, whereas we showed that this is not the case. In summary,
they ignored the decision of USP to modify after USP 24 the dissolution
medium from 0,1 to 0,01 molar. Up to today they are producing Quinine
not passing present USP requirements for dissolution.
4. How do we warn effectively about falsified products to avoid harm
for patients?
We recently discovered a fake Coartem batch (batch F 1901/Exp 1.2014) in
Cameroon through the Minilab system (result confirmed by
WHO-prequalified lab in Kenya). The WHO published a drug warning alert
(Alert 127) but the company replied that they had been aware already
about problems with this product, falsified batches had been identified
before in Ghana, Nigeria, Angola and Cameroon and authorities were
informed. Is this enough to warn the medicine and poisons boards only?
Who is warning the public, the medical and pharmaceutical professionals
to avoid ineffective treatment? How can we introduce a warning system in
these countries to avoid human deaths because of ineffective medicines?
Buying from reliable and registered sources/facilities may be one step.
But many patients cannot reach a health facility and are dependent on
local pharmacies. Malaria Tablets might be free of charge in the health
facility but public transport is expensive, waiting queue is long and
often consultation or lab must also be paid.
Another very present case story from Cameroon as well: DuoCotecxin,
according label produced by Zhejiang Company in China / LOT 010906, EXP
09/2015 found in the private market recently without active ingredients
(additional packages same batch bought today for further testing,
therefore still in the market!). According to my partner this is being
sold in Douala for 1000 CFA and widely used in private settings. How can
we avoid harm to patients that are buying these ineffective tablets
because they are so cheap?
But if necessarily the number of warning letters will increase – how to
build trust back in patients’ hearts that medicine is effective, good
quality and life saving? That becomes a very big challenge.
The World Health Organization is in the process of extending the global
surveillance and monitoring system with the aim to increase reporting
rates for counterfeit medicines and, thus, obtain reliable estimates of
incidence levels and harm caused by counterfeit products.
But more is needed: exchange of information on falsified products
through local and international networks and the interest and
cooperation of originator companies to look beyond market shares and
assist in removing the falsified ones off the market. This is an urgent
matter as more and more falsified medicines are entering the markets.
How can we use the pharmacovigilence databases in this regard not only
identifying but also following up on falsified products?
*Conclusion*
The issue of quality standards of medicines has to be discussed and
quality systems implemented at all levels of health care. Staff need to
be trained to notice a suspected product if the label is not in good
order, if the expiry date is not stamped/embossed or unreadable. Workers
in all levels of the pharmaceutical profession have to be aware that
procurement of medicine needs a strong focus on quality and not only on
price.
Local QC-labs in the field have to be strengthened. Curricula have to be
modified and updated to include QC awareness.
[I would argue that curricula need to specifically include some time on counterfeits/SSFCs including problems, supply chain security, identifying and reporting SSFCs. DB]
Ideas and comments are appreciated.
Albert Petersen
Pharmaceutical Department
Difäm
German Institute for Medical Mission.
Paul-Lechler-Street 24
D-72076 Tübingen
phone: +49 7071 /206-531, fax: +49 7071 27125
eMail: petersen.amh@difaem.de
web: www.difaem.de
Chair of Ecumenical Pharmaceutical Network (EPN)