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Suspected falsified Hepatitis B Vaccine, shows remarkable similarities with genuine Hepatitis B Vaccine (rDNA) supplied by Government of Uganda

Friday, 27th April 2018

Suspected falsified Hepatitis B Vaccine, shows remarkable similarities with genuine Hepatitis B Vaccine (rDNA) supplied by Government of Uganda
 1)    INTRODUCTION & BACKGROUND

During routine post market surveillance visits by the National Drug Authority (NDA), 48 standalone labels of the 10ml multi-dose Hepatitis B Vaccine (rDNA) manufactured by the Serum Institute of India (SII) were picked from High Street, Mbarara Municipality in March 2018.

This finding raised suspicion of possible falsification of that particular packaging unit of the vaccine, leading to a sting operation by NDA in 18 drug outlets mainly in Western and Central Uganda. Falsified medical products are defined as medical products which deliberately or fraudulently misrepresent their identity, composition or source. A genuine pharmaceutical product which is re-labelled fraudulently is also considered as falsified.

  • Altogether 192 suspected 10 ml units of Hepatitis B Vaccine (rDNA) purportedly manufactured by the Serum Institute of India were confiscated by NDA and forwarded to the National Drug Quality Control Laboratory (NDQCL) for further investigation.

  • Pre-printed vaccination cards of Sanyu Medical Centre were discovered, said to have been used during an immunization camp at Mbarara University. Organisers of the camp said they have always gotten their vaccine from a Mr. Kayongo of Sanyu Medical Centre since November 2017.

Since then, several actions have taken place so as to establish the actual contents and composition of the suspect vaccines, how they came to the market and who the culprits are as well as how wide-spread is the problem. This will inform NDA on how to plug the holes identified and avoid re-occurrence of such in the future.

 2)    ABOUT HEPATITIS B VACCINES IN UGANDA

a)    Hepatitis B Vaccines in Uganda: There are a number of registered brands of Hepatitis B Vaccine in Uganda from various manufacturers worldwide (India, Belgium, South Korea & France) represented by local pharmaceutical companies. Below is a list of the registered license holders and the pharmaceutical companies which represent their interests in Uganda.

LICENSE HOLDER   
 LOCAL REPRESENTATIVE BRANDCOUNTRY OF ORIGIN
Sanofi Aventis Kenya Ltd
 Laborex Uganda Ltd SHANVAC-B India

 GlaxoSmithKline Pharmaceutical Kenya Ltd Eris LtdENGERIX-B VACCINE Belgium
 Biological E. LtdGittoes Pharmaceuticals Ltd BEVAC India
 Serum Institute of IndiaNorvik Enterprises Ltd HEPATITIS B VACCINE (rDNA) India
 Pasteur Merieux CONNANGHTLaborex Uganda Ltd
 EUVAX B South Korea
 Indian Immunologicals Ltd. Tata Uganda Ltd ELOVAC-B India

Registered Sources of Hepatitis B Vaccines for Uganda

 3)    ACTIONS TAKEN

a)    Verification with the Manufacturer

Preliminary findings indicated that the falsification affected only the 10 ml multi-dose Hepatitis B Vaccine (rDNA) manufactured by the Serum Institute of India which is supplied to the Government of Uganda for use in government facilities where it is free. The 1ml single-dose ampoule is largely used in private hospitals where it is sold. In a statement the manufacturer (Serum Institute of India) through its local representative Norvik Enterprises, had this to say about the suspect samples:

  • Lacked the red in-print on the labels with "Government of Uganda - for public use not for sale"

  • Some of the impounded samples, bore a batch number (035L006) that was never manufactured by SII

  • Some of the suspected samples had a manufacturing date inconsistent with that manufactured authentically and two batches had expiry dates inconsistent with the ones manufactured.

  • Some samples, bore authentic batch numbers but those vaccines were only supplied to India and to Mexico. Those supplied to Mexico had labels in Spanish yet those captured from the Ugandan market were in English.

We have also established that:  

  • The consignments received by Norvik Enterprises tallied with the consignments dispatched by the manufacturer in dates, quantities and batch numbers.

  • The inscription "Government of Uganda- for public use, not for sale" on ten of the vials recovered appears to have been erased.

  • A batch (035L006) of ten vials had a different colour scheme and label design compared to the one from SII.

  • There were inconsistencies in the shelf life of the various batches as reflected by the expiry dates. For example, vials with the same batch number (035L6010) were found to have three variations in the date of manufacturing and expiry.


b)    Arrests & Prosecution

Working with the Uganda Police, we have been able to positively identify suspects from the 18 medical centres and drug outlets where the falsified samples were found. Ten case files have been opened so far at the police. The case reference numbers are: MBBRA CRB 700/18, CRB 616/18, CRB 608/10, 613/18, 614/18, GEF 03/18, CRB 435/18, GEF 094/18, GEF 318/18 and E/93/2018. One of the files has been sanctioned and hearing took place on 28th March 2018 and the suspect, Bira Maclean linked to Mackie Laboratory in Kampala, has been convicted and remanded to Luzira prison.  Other suspects have been arrested and a few are on the run. At this point, we do not wish to reveal the suspects' names for fear of compromising the investigation.

A challenge faced in this regard was that most of the suppliers of the falsified vaccine delivered to the clinics they supplied so their physical locations were not known by the recipients or end users. Some of the invoices that accompanied the deliveries of the vaccine were fake and could not lead investigators to the stated physical locations.


c)  Laboratory investigations and findings

The suspect samples- the 10ml vials purportedly manufactured by the Serum Institute of India (SII) together with genuine Hepatitis B Vaccine (rDNA) samples from Serum Institute of India (SII) were subjected to qualitative tests at the National Drug Quality Control Laboratory (NDQCL):

  • Visual inspection. The physical appearance, primary packaging material and closure systems of both samples were examined.

  • Physico-chemical test were performed including pH and  extractable volume tests and Identification tests using High-Performance Liquid Chromatography (HPLC) technique


The findings by the lab were that:

i)    Both the suspect and genuine 10ml multi-dose samples had similarities in the physical appearance, primary packaging material and closure systems.

ii)    Both samples were found to comply with both the manufacturer and the United States Pharmacopeia (USP) specifications similar pH and extractable volume test results- compliant.

iii)    The only visible differences are observed in the external labelling- much as both samples bore a purple band at the bottom and top of the 10mls pack, the labels appeared different. It was observed that the inscription of  "Government of Uganda, Public Use Only, NOT for Sale" appeared to have been erased from some of the suspect 10mls vials.


 d)    Collaboration with World Health Organisation (WHO)

i.    World Health Organisation offered technical assistance to do confirmatory tests  on the falsified vaccine at the United Kingdom's Medicines and Health Products Regulatory Agency (MHRA) laboratory.  Specifically, these in-vivo and in-vitro tests confirmatory tests involve;

  • Identification of the Hepatitis B surface antigen (HBs Ag)
  • The ratio of HBs Ag content to protein content
  • Bioassay
  •  Residual chemicals, possible contaminants and impurities
  • Microbial purity (absence of bacteria and fungi)


Preliminary results from the MHRA

Preliminary results from the MHRA, contained in a 25th April 2018 report indicate that:

  • There were visible differences in labelling between the genuine Hepatitis B vaccine and the falsified samples, consistent with findings at the NDQCL laboratory.

  • There was no Active Pharmaceutical Ingredient (API) in both samples i.e. there were no residual chemicals, contaminants, bacteria or fungi that could cause any adverse effects after administration.  


We are waiting for a comprehensive report from WHO and MHRA that covers the full range of confirmatory tests.


ii.    NDA also reported the falsification to the World Health Organisation Rapid Alert System (RAS) and worked closely with the RAS team to develop and disseminate an international alert for the falsified Hepatitis B vaccine.

iii.    Four (4) NDA officers have received WHO-funded training to enhance skills in the detection and response to substandard and falsified products on the market.


e)    Additional activities

  • There is ongoing field monitoring of people who received the suspect vaccine by the NDA Vaccine Pharmacovigilance teams to report any adverse events. So far no adverse event has been reported. The adverse event reported by NBS TV and attributed to Hepatitis B vaccine was found to be untrue. Our investigations show that the patient's swelling of the arm, about 5 centimetres below the injection site, was unrelated to the vaccine she received.

  • NDA in collaboration with the Ministry of Health will organize training for staff of accredited private health facilities on good vaccine distribution practices.

  • To increase on the capacity of our current laboratory, NDA is fast-tracking the establishment of its state of the art microbiology laboratory that will significantly increase the scope of testing.


 f)    CONCLUSION

The findings from our laboratory and the UK MHRA laboratories, so far indicate that the falsified vaccine is highly likely to be Hepatitis B Vaccine (rDNA) from Serum Institute of India (SII) delivered to Government Health facilities but diverted along the supply chain and sold to private medical facilities.

We continue to urge the public to increase their vigilance, not for just the Hepatitis B vaccine but all medicines. All licensed dealers and pharmacies are required to prominently display their licenses at their premises. We urge the public to make use of our Toll Free Line (0800 101 999) to report falsified medicines and suspicious vendors.

 ACKNOWLEDGEMENTS

We wish to thank the public for your patience during this time. We also wish to thank the Ministry of Health, National Medical Stores, Uganda Police Force and the Health Monitoring Unit for their unwavering support in addressing this crisis.