Dear Honourable Minister,
Still on Ineffective Anti-Snake Serum & Procurement Breaches- Evidence Finally.
Greetings. Once again, let me congratulate you on the revered references your ministry received from the President when he addressed the nation two and half weeks ago. I have since monitored your feet-on-ground duties to either resuscitate dilapidated health facilities or complete abandoned ones.
We still have unresolved matters on the subject of this letter. By the way, thank you for your earlier responses, which were also shared with the public. Since you indicated, that, should we require further clarification, your office will duly oblige, we are following up on two critical issues.
We have noted your response to our previous concern that, the “bid evaluation rigging & overly intrusive interventions in the tender process.” We reference your answer:
MINISTRY’S ANSWER: I will like to explain that there was no bid evaluation rigging as alleged in your letter. In accordance with the provisions of the Tender documents, clause 30(1) and also section 57 of the Public Procurement Act 663 as Amended (Act 914). A letter was written to two of the tenderers for correction of arithmetic errors, which was detected during the evaluation process. There was no attempt to give the two tenderers competitive advantage. I will like to state emphatically that the correction of error did not result in any change of unit price. The error detected during the evaluation was that, the tenderers should have multiplied the unit price by the pack size and the quantity required. They however multiplied the unit price by the quantity and left out the pack size, which resulted in an error in their total bid price.
IMANI’s CONCERNS: Clause 27 and 30(1) of the Tender document (attachment 1) as well as Section 57 of the Public Procurement Act (Act 663 amended) gives the Ministry the right to correct arithmetic errors, detected during the evaluation process. In clause 27 it says “During the evaluation of the tenders, the Purchaser may at its discretion, ask the Tenderer for a clarification of its tender”. It further continues as “… no change in the price or substance of the tender shall be sought, offered or permitted, except to correct arithmetic errors identified by the Purchaser in the evaluation of the tenders.”
Clause 30.1 clearly explains what an arithmetic error is and how it should be corrected: “Arithmetic errors will be rectified as follows: If there is a discrepancy between the unit price and the total price that is obtained by multiplying the unit price and quantity, the unit or subtotal price shall prevail. If there is a discrepancy between the subtotals and the total price, the total price shall be corrected. If there is a discrepancy between words and figures, the amount in words will prevail.”
Therefore, it is very clear how to deal with arithmetic errors when they occur. Based on the evidence, which we have attached (attachment 2), it would seem that the Ministry of Health instead asked the two Pharmanova companies to change their unit costs and total costs after the public opening of the tender.
Find attached the original price schedules which were presented at the tender opening (attachments 3 & 4) and which were backed by the original bid securities (attachments 5 & 6).
See the original price schedule template form the tender document (attachment 7) which was supposed to be used while the one used by the Pharmanova companies differ.
It would appear that what the ministry did was no correction of arithmetic errors. Would we be wrong?
It also appears that the two Pharmanova companies are actually one and the same company which means that there was double/alternative bidding involved in this tender which is illegal but we will visit that matter later.
QUESTION 5: “Isn’t it the case that the World Health Organisation has concerns about the efficacy of the anti-snake serum the company you are reported to have requested through sole sourcing, to supply Ghana with the serum?”
MINISTRY’S ANSWER: It is not true that WHO has concerns with the efficacy of the Anti-Snake Serum from the company in question. There is no documentary evidence to prove this.
IMANI’s CONCERNS: Honourable Minister, unfortunately, we have further concerns and evidence of WHO’s concerns about the potency of anti-snake serum produced by this company/ manufacturer (VINS/Pharma nova). See below.
Snake Antivenom for Sub-Saharan Africa Dossier Review Notification
Company/ Country: VINS Bioproducts/ India
Date / WHO Reference No: 6 April 2017 PQT-CRH/adb 2017- 049
We have sighted a letter from the WHO Prequalification Team (PQT) to the Indian drugs regulator (our FDA equivalent) referenced above, terminating “the assessment of the dossier of Snake Antivenom for Sub-Saharan Africa” submitted by VINS Bioproducts Limited, the lead partner of the company whose tender is at the heart of this procurement dispute. In a cover note to Dr S. Eswara Reddy, the Head, Biological Division, Drug Controller General India (DCG (1) of the Central Drugs Standard Control Organisation (CDSCO), Ministry of Health & Family Welfare, Government of India, the WHO Prequalification Team (PQT), noted that it “has communicated to the manufacturer that we are informing you as the relevant authority.”
The decision to terminate the assessment of VINS’ antivenom is in part due to the conclusion “The panel of experts has also considered recently published data by Calvete et al (2016)[1] that determined that with respect to the neutralisation of venom from Echis ocellatus (from Cameroon, Mali and Nigeria) that the VINS product they tested “was ineffective in neutralizing lethality, at the maximum dose of antivenom tested, and showed low efficacy in neutralization of the in vitro coagulant effect. According to the product insert, one Ml of this antivenom should neutralize not less than 25LDsos of E. ocellatus venom. Since the LDso of the E ocellatus from Cameroon is 33µg per mouse (Sanchez et al. 2015), this means that one ML of this antivenom should neutralize not less than 825 µg of venom; however, the ED50 of the batch tested in this study is lower than 250 µg venom per mL antivenom.” Given the medical importance of Echis ocellatus as a cause of envenoming across a large region of Sub-Saharan Africa, this poor neutralizing potency suggest that this product should not be recommended for use in Sub-Saharan Africa, at the current time, although this position could be reconsidered in a future assessment of antivenoms if data from the manufacturer or other sources becomes available to demonstrate improved potency, and/or evidence of clinical effectiveness from authenticated clinical studies.’’
There are more reasons for termination;
Status of the Application
The panel of experts has considered the dossier and the supplementary information that was sought and has determined that the application cannot progress to a further stage of the evaluation and that no further consideration of the application can occur at this time
Basis for the Decision
This decision has been made for the following reasons:
- In relation to the issue of the clinical trial data resulting from the manufacturer-sponsored study in the Congo, the manufacturer claims the study was independent. Given that the manufacturer is listed in the dossier as having funded this study, this argument is untenable. The complete response from the manufacturer to this serious matter is shown below:
“As mentioned in “Data requirement in the application process” as part of clinical data we have mentioned that clinical trials are not performed and only studies have been done. These studies have been done by independent researchers. We apologize on providing the reports unchecked. It is clear that something went wrong and we are investigating. Hence we require some time to probe the content. We shall provide information when it comes in hand.”
As the name of the sponsor of the study the manufacturer has the responsibility under the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Good Clinical Practise (GCP) Guidelines for:
“5.1.1 The sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data are generated, documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory authorities.”
5.1.2 The sponsor is responsible for securing agreement from all involved parties to ensure direct access (1.21) to all trial related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities.”
The authors of the clinical trial study were contacted by the panel of experts and they were asked to confirm their authorship to the report, and the financial support for the study by the manufacturer. In the case of one author, Dr Kate Jackson, a herpetologist from Whitman College in the United States, Dr Jackson was asked to confirm her identification of specimens of snakes as reported in the study. In her reply, Dr Jackson states in writing that:
“If the study was conducted I really don’t know. Which clearly indicates that my involvement has not been sufficient to merit authorship. However, I don’t know that they didn’t carry it out and possibly they were including my name as honestly well-intended gesture for my very small involvement early on and not for any disingenuous reason. That said, I did not identify any snakes for the study and I would urge the WHO to press them for details and evidence that they did what they say they did.”
In addition, we received the following response from Dr Etienne Mokondjmobe, Director of Laboratoire National de Sante` Publique in Brazzavile, Congo, who was another of the nominated authors of the study:
“First you will excuse my late reply to your important letter given the issues raised which involve health and ethical matters.
After reviewing all the documentation and the relationships amongst the authors mentioned in your email, we can say that some actors, especially those working in The Republic of Congo and precisely in Brazzaville belong to the same scientific team that has worked on the issue of anti-venoms, and thus maintain a collaborative relationship with other scientist working in other geographical regions of the country. But never did I participate in the study entitled “Clinical Safety of VINS polyvalent F (ab`) equine anti-venom in 112 African Snake envenomation: a field trial Brazzaville, Congo.”
Since the other questions follow from the first, the answers are all negative.
Ultimately, I am totally unaware of this study.
Dear Colleagues,
I hope this response will help you make decisions that are consistent with ethics and good bio-clinical practice and that you will keep me informed of the decision.”
These responses cast very serious doubt over the authenticity of the study. Given that the study was sponsored by the manufacturer to ensure that the contracted research is undertaken and undertaken honestly and accountably. The panel of experts is not satisfied that there is evidence of the study having been conducted as claimed.
- The panel of experts has also considered recently published data by Calvete et al (2016)[2] that determined that with respect to the neutralisation of venom from Echis ocellatus (from Cameroon, Mali and Nigeria) that the VINS product they tested “was ineffective in neutralizing lethality, at the maximum dose of antivenom tested, and showed low efficacy in neutralization of the in vitro coagulant effect. According to the product insert, one Ml of this antivenom should neutralize not less than 25LDsos of E. ocellatus venom. Since the LDso of the E ocellatus from Cameroon is 33µg per mouse (Sanchez et al. 2015), this means that one ML of this antivenom should neutralize not less than 825 µg of venom; however, the ED50 of the batch tested in this study is lower than 250 µg venom per mL antivenom.” Given the medical importance of Echis ocellatus as a cause of envenoming across a large region of Sub-Saharan Africa, this poor neutralizing potency suggest that this product should not be recommended for use in Sub-Saharan Africa, at the current time, although this position could be reconsidered in a future assessment of antivenoms if data from the manufacturer or other sources becomes available to demonstrate improved potency, and/or evidence of clinical effectiveness from authenticated clinical studies.
The decision of the panel of experts relates to the application of the manufacturer to have the antivenom product considered for the listing by WHO of this product on the WHO website as a product suitable for use in the treatment of snakebite envenoming in Sub-Saharan Africa. In the vent that WHO calls for any further Expression of Interest for the Assessment of Antivenoms for sub-Saharan Africa at some future time, nothing contained in this decision shall exclude or prevent the applicant from resubmitting a complete and comprehensive product dossier that addresses the information requested by the new call for Expressions of Interest for Evaluation”
| WHO Focal Point: | Carmen Rodriguez Hermandez |
| Reviewer: | Panel of Experts |
| Dossier submission date: | 24 February 2016 |
| Date of Notification: | 6 April 2017 |
IMANI’s FINAL QUESTIONS: Honourable Minister, are you aware if VINS Bioproducts Limited along with its partner, Pharmanova, at the heart of the procurement disputes has initiated another set of clinical trials in 2018 and if yes, can you provide the evidence?
Don’t the glaring contradictions make this tender process noncompetitive? Would we be wrong to conclude that the entire procurement process is skewed to favour an unqualified service provider with potential health hazards for the country?
As always we remain at your service.
Sincerely,
Franklin Cudjoe (signed)
On behalf of Ghana.
Cc: Hon. Kingsley Aboagye Gyedu (Dep. Minister MoH
Chief Director, MoH
Dr. Nsiah-Asare (DG, Ghana Health Service)
Mr. Charles Taylor (Chairman Central Tender Review Committee)
Ghana Medical Association
CHRAJ, GACC, GII, Media, MFWA
Source: Ghana/Starrfm.com.gh/103.5FM
