[e-drug] Substandard propofol supplied by UNIMED in Zambia (10)

e-drug
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E-DRUG: Substandard propofol supplied by UNIMED in Zambia (10)
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[Yet again- here is emphasis of the importance of having a strong and efficient regulatory authority that checks the quality of suppliers and products BEFORE authorisation to import/procure - to ensure that only products of certified standards are imported. BS]

Dear E-Druggers,

I am a pharmacist and part of the research group of Prof. Lutz Heide at
the Pharmaceutical Institute of Tuebingen University, Germany.

This case of substandard propofol in Zambia reminds me very strongly of
a misoprostol case we experienced during our studies in Malawi.

The University of Tuebingen and the University of Malawi carry out a
joint study on the quality of oxytocics in Malawi. Misoprostol tablets
and oxytocin injections are sampled at different points of the supply
chain, and they are analysed according to the methods of USP and Ph. Int.

In this ongoing study, one extremely substandard brand of misoprostol
tablets was identified. It showed only 13% of the declared content of
the API, dissolution testing showed that only 8% of the API dissolved.

This brand is stated to be produced by Swiss Parenterals PVT. Ltd.,
Gujarat, India (which is not placed in Switzerland and mainly produces
oral dosage forms) and distributed by Premiumway International U.K.
(who does not give a postal address on his website
www.premiumway.co.uk/).

In Malawi, it had been distributed by the Malawian Central Medical Stores Trust (CMST) to all government health facilities. We informed the national drug regulatory agency of Malawi as well as CMST and WHO of the findings in January 2018. Notably, all responded immediately.

The national drug regulatory agency (Pharmacy,
Medicines and Poisons Board of Malawi; PMPB) issued a product recall.
CMST discontinued supplying the substandard brand and replaced it with a
brand identified to be of good quality.

I will present this case at the Medicine Quality and Public Health
Conference 2018 in Oxford this September.

Kind Regards,

Nhomsai Hagen

Nhomsai Hagen
Apothekerin, Doktorandin
Eberhard Karls University Tuebingen
Pharmazeutische Biologie, Pharmazeutisches Institut
Tuebingen
nhomsai.hagen(at)uni-tuebingen.de

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E-DRUG: Substandard propofol supplied by UNIMED in Zambia (11)
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Dear e-druggers,

It is sad to see that still there are suppliers in Europe supplying substandard medicines to so-called developing countries, taking advantage of their limited capacity in evaluating medical products.

Therefore the list of products registered in Europe posted on E-drug earlier is a useful tool:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2018/07/WC500252703.xlsx

In the past I have experienced that suppliers claim that their products are registered in European countries, which appear to be untrue. The list above is therefore helpful to verify such claims from suppliers.

regards

Truls Eriksen
truls@eurokom.no

[Moderator checked the EMA database but did not find any products of UNIMED International or Kwality Pharmaceuticals registered in Europe.
The same applies to the database of Zambia registered products. WB

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E-DRUG: Substandard propofol supplied by UNIMED in Zambia (13)
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[The original message on August 17 explains. Some details added below Minzi's message. BS]

Dear E-drug
This is not a good trend. How was substandard propofol detected in Zambia
considering limited lab analysis capacity?

Rgds

Minzi

[Moderator's insertion: From August 17: BACKGROUND:
In early 2015, clinicians throughout Zambia noted a range of unpredictable
adverse events after the administration of propofol, including urticaria,
bronchospasm, profound hypotension, and most predictably an inadequate depth
of anesthesia. Suspecting that the propofol itself may have been
substandard, samples were procured and sent for testing.
METHODS:
Three vials from 2 different batches were analyzed using gas
chromatography-mass spectrometry methods at the John L. Holmes Mass
Spectrometry Facility.]

Minzi Omary Mashiku Sylivester
Professor of Clinical Pharmacology at Muhimbili University of Health and
Allied Sciences (www.muhas.ac.tz)
Omary Minzi <minziobejayesu@gmail.com>

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E-DRUG: Substandard propofol supplied by UNIMED in Zambia (14)
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Dear e-drug friends,
I hope Professor Minzi's question does not give the impression that only through laboratory analysis can a substandard product be DETECTED. In fact, from my own published work on this subject over three decades ago, laboratory analysis is many times just a confimatory; sometimes unnecessary, step. For example, if by visual examination I see clear evidence of fungal growth in a Normal Saline IV infusion, there is no value addition by carrying out a flame photometric analysis for levels of sodium and/or chloride ions.

I am personally sometimes saddened when the subjec of substandard or related subject is presented in a "Eureka" context!!

Murtada Sesay

Pharmaceutical Systems Consultant
Sierra Leone
Murtada Sesay <kindiatown@hotmail.com>

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E-DRUG: Substandard propofol supplied by UNIMED in Zambia (15)
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Dear Murtada, and all,

yes, visual presence of microbial growth is effectively a good enough
reason to remove and dispose the lot. Keeping a few units segregated as
objective evidence (for lab testing) would in my view still be highly
advisable!

The above we can perhaps call "visible sub standard" drugs (vSS). The
(much) larger issue in markets is potentially with "not visible,
sub-standard" products (nvSS) on the shelves; NvSS are without visible
signs of contamination nor showing signs of physical deterioration, and
could include high quality fake product sold as medicine. This nvSS
category may have some kind of effect in a patient but due to the
substandard nature these actually prolong or worsen disease and lead to
treatment failure, unexpected side effects and possibly ADRs and ADEs.

More disability and more cost could have been avoided, probably, with more
prospective QC testing of medicines taking place post-marketing i.e.
actually sampled from the market as opposed to 'after a product has been
registered by an NRA' (the latter typically misses products in the market
that have not been registered)

There are quite a number of QCLs now world wide pre-qualified by WHO or
certified by others to be approached for sampling and QC testing of
medicines.

Around Zambia there are at least 3 labs in the South Africa;
Post-market surveillance is to be paid from the regulatory fees received
from applicants for registration and periodic re-registrations. What are
the other hurdles?

Meanwhile also looking forward to comments on the Propofol case in Zambia
from the source and/or the exporting NRA in India, Drug Controller in
Punjab State.

best regards,

Pascal

Pascal Verhoeven
MPH/pharmacist
June-October 2018 ADB consultant for ABEC pilot
Kazakhstan/Kyrgyz Republic