E-DRUG: Substandard propofol supplied by UNIMED in Zambia (3)
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[I believe an effective regulatory system that checks GMP and other standard quality etc requirements- as explained by Wilbert in the second message - are crucial to avoid import of substandard products, The post-marketing surveillance and pharmacovigilance are also essential. BS]
Dear E-Druggers,
a compelling case to advocate for implementation of post
marketing surveillance (prospectively), especially where origin of product
and its GMP status is not directly known (i.e. via 3rd parties i.c. UNIMED
allegedly without a MQAS type of assurance system in place. Or where
national procurement laws in LMIC unfortunately still dictate price over
quality.
1- As the action by ZAMRA had to be reactive, the additional question for
me is to learn more about the reasons for the absence of an implemented
risk based post marketing surveillance framework that would indeed
prospectively sample and test medicines from hospital sites (*see 2 below,
perhaps). Also it has been argued before that in the case of Zambia the
procurement of medicines should transfer from MOH to the Stores (MSD) that
links with ZAMRA and would not give ways to bypass the regulatory checks.
2- Pharmacovigilance and Post-marketing surveillance are different things. The monitoring of medicine quality in health facilities under a
'pharmacovigilance' passive reporting system may result in NRA/s
implementing the one but not the other. Adverse Drug reactions link to the
drug compound itself and are consistent with the summary of product
characteristics and its safety evaluation (e.g. propofol: hypotension,
dizziness, rash, pruritis...). ADRs can therefore be classified as effects
that are not at all necessarily caused by substandard product quality or a
particular source. Unexpected ADRs are not consistent with the summary of
product characteristics) and negatively affect the safety profile of the
product from that particular source.
As stated by Pisani et al*, reporting
systems based on 'pharmacovigilance' to capture and investigate
(unexpected) ADRs will tend to overstate the proportion of toxic medicines
i.e. contaminated or falsified products or those with lack of efficacy. It
is however the potentially larger group of substandard quality drugs
circulating in the markets i.e. those from a genuine source that provide
some kind of effect in a patient but actually prolong the disease, that are
least likely to be reported under a pharmacovigilance system as these can
only be identified by sampling the product followed by screening and actual
quantitative testing in a qualified laboratory.
*Antimicrobial Resistance and Medicine Quality. Pisani for AMR Review,
November 2015
3- What i find not reconciling well from reading the messages is batches
having "only 64% and 93% active content", with the reported lack of
efficacy reported by the the sites (the initial reports were from the
University Teaching Hospital in Lusaka, Ndola and Monze were all on lack of
efficacy); we don't know if in the clinical practice in Ndola and Monze,
the dosage may have been increased (from same vial) in order to elicit
effect, that has triggered more or unexpected adverse reactions; (whereas
the teaching Hospital in Lusaka for instance may have had access to an
alternative (ketamine).
The initial article reported that no (hexane soluble) impurities were identified by GLC/MS. Both QCLs reported low assay results, but neither QCL tested for identity of excipients (notably glycerol vs propylene glycol), tested for levels of related substances (USP Propofol Related Compound A RS, and USP Propofol Related Compound B), tested for sterility or microbiological contaminations (e.g. under USP
standards it is not an antimicrobially preserved product because it is
intended solely for single use/single patient).
looking forward to other views or thoughts on these,
best regards
Pascal Verhoeven
Pascal Verhoeven
MPH/pharmacist
June-October 2018 ADB consultant for ABEC pilot
Kazakhstan/Kyrgyz Republic
Pascal Verhoeven <verhoeven.pascal@gmail.com>