Procurement of Heberon by DoD: SAHPRA & DoD briefing; with Minister

Meeting report

Briefing by South African Health Products Regulatory Authority (SAHPRA) on procurement of Heberon

Prof Helen Rees, Chairperson, SAHPRA, gave a brief background of SAHPRA and how it worked. She said that it was important that the health system had drugs that were safe and approved by the regulator. SAHPRA was there to make sure that drugs that were imported into the country were licensed, and there different ways in which drugs may be approved.

Dr Boitumelo Semete, Chief Executive Officer (CEO), SAHPRA, said that SAHPRA may, in certain circumstances, and in accordance with Section 21 of the Act, authorise the sale of an unregistered medicine for such purposes and in such manner and during such period as the Authority may determine. A Section 21 authorisation was to provide access to unregistered medicines on an exceptional basis, where conventional therapies had been ruled out, had failed or were unavailable as marketed products. It was also used when clinical trial enrolment was not a possibility.

On 27 August 2020, SAHPRA had received a new application for bulk stock of Heberon (Recombinant Human Interferon alpha-2b). No quantities were mentioned, no further information was supplied on the clinical benefit, and the application was rejected. On 5 October, SAHPRA had received a named-patient authorisation request “to boost defence against COVID-19 complications” for the use of ten vials of Heberon, and the application was approved. On 21 October, SAHPRA had received a bulk stock authorisation request for Heberon, where no quantities were mentioned, no further information was supplied, and the application was rejected with a recommendation that all relevant details about the application be submitted to SAHPRA.

Dr Semete said that SAHPRA became aware of the matter of Interferon alpha 2B being in the possession of the South African National Defence Force (SANDF) in November. The product had been imported by the SANDF without SAHPRA authorisation in November. SAHPRA inspectors had first engaged with Lt Col Oma Mohammed, the Pharmacist responsible for the SANDF on 11 November. At this meeting, Mr Mohammed had referred SAHPRA inspectors to Col Lorraine May, who was the officer in command for Military Health Services, but numerous attempts to reach Col May had failed.

SAHPRA had visited the SANDF’s military health base depot in Pretoria on 29 January 2021, together with the HAWKS. The general practice of SAHPRA, when investigating facilities that were not licensed by SAHPRA, was to be accompanied by the South African Police Service (SAPS) or the HAWKS. Col May had availed herself for this visit, but had requested postponing the meeting after SAHPRA informed her of the reason for the visit. SAHPRA Inspectors had requested to inspect the consignment, and Col May had agreed. The medicines were adequately stored in a cold room in the warehouse. Meetings to discuss a way forward, scheduled for 3 February, did not proceed.

SAHPRA met SANDF on 9 February to align on the developments, and a follow-up meeting was held on 12 February. The parties discussed the proposed way forward on Heberon. It was agreed that SANDF would submit a clinical trial application for the product, SAHPRA would, on receipt of the clinical trial application, expedite the review, as had been the case with other COVID-19 clinical trial applications. A small technical team from both parties would be constituted to look at the technical requirements prior to the submission. SAHPRA and SANDF would issue a joint press statement.

SANDF presentation

Lt Gen Zola Dabula, Surgeon General, SA Military Health Service (SAMHS), introduced the SANDF team which was stationed in Pretoria, as they were going to be engaging with the Committee through the presentations. He also said that the media had reported some of the issues incorrectly.

The Chairperson asked Lt Gen Dabula to talk about the procedures which had been followed to procure the drug into South Africa, and not include what had been written in the media, because it would side-track the meeting. The Committee also wanted to know the side of SANDF on the findings of the Auditor- General of SA (AGSA).

Lt Col Thabo Mnisi, Head of Department (HOD), SAMHS, said that the AGSA had made their findings based on four focus areas which included the deployment of soldiers to various provinces to assist with enforcing law and order, the implementation of additional health measures, including establishing quarantine sites, laboratories and field hospitals with the necessary equipment and procurement of personal protective equipment (PPE).

At the beginning of Covid-19 pandemic, there was no single drug that could cure Covid-19. All drugs were experimental, and Force Protection had become the best option against a pandemic that had no cure according to experts and available evidence then. Additional biological measures to supplement known etiquettes, such as sanitisation, social distancing, cough etiquettes and others in the absence of credible vaccines had been explored. The SANDF had looked into what countries that seemed to have lower mortality rates per 1 000 were using. They felt that since they were going to be deployed in hotspots, they needed an Iinterferon boost, as the virus was known to target natural interferons. The interferon and other Covid-19 related drugs were sought after by many countries affected by the pandemic. It was during the time that zinc and chloroquine were procured by other countries in such large quantities that they were scarce.

It was imperative then, in March 2020, with the borders closing and China procuring Cuban interferon in large quantities, to procure the drug before it was either not available or escalated in price due to demand.

Active SANDF members, both uniformed and Public Service Act Personnel (PSAP), Reserve Force members and VPA members, and other SAMHS beneficiaries who would need interferon boosting, were numerically well above what could be procured at the time. This could cover only 23 000 active members and call-ups for a period of two years with consistent cover. However, the SAMHS had to cover a total of 260 000 of its client bases.

Ten vials had been administered on a patient, and the patient had fully recovered without any complications within seven days of its administration, in that he had regained his energy and the symptoms had disappeared.

Psychologically, the morale of the soldiers had been heightened by the awareness of available protective drugs, and the impact would have been more positive with fewer sick leave days had they been granted bulk approval for military use.

The SANDF understanding at the time was that due to the State of Disaster Declaration and shared information on the intention to use several drugs on an emergency basis, as the lockdown was at level 5, SAHPRA would clear the emergency-procured drugs upon application for Section 21 of Act 101 of 1965.

It became apparent to the SANDF that the normal application processes, which included Section22 of the Act, ought to have been fully explored irrespective of the urgent state it found itself in, as many sectors were either shut or working with skeleton staff.

SAHPRA approval for importation was not secured by the Department of Defence (DoD) at the time due to the urgency to secure this medication within our borders before it went off the shelf at the time. The integrity of the drugs was protected.

Col Mnisi said that none of the drugs were damaged in any manner, as they had monitored conditions under which they were stored according to the manufacturer’s specifications. SAHPRA had been engaged several times, and the first approval was sent back, as it had no specific name of patient.

The SANDF intended to smooth relations with SAHPRA through dialogue, and optimise communication with the national Department of Health (NDoH) at all levels to utilise the medication for Force protection before the onset of the third wave of the pandemic so that soldiers could be healthy to support the government whenever required. Qualified medical doctors within the SAMHS from the Department tasked with preventive medicine outside hospitals, would administer the drug the same way they did before with the approval of the ten vials.

Two webinar clinical discussions had been held with Cuban specialists, one was held with China, and another with Vietnam. The national protocols did not have a position on the use of interferon for immunomodulation, but encouraged clinical trials on its use beyond hospitalised patients where consensus remained undisputed.

The investigation commissioned by the Minister would come up with concrete recommendations and where consequences/action should be taken, the Department would do so. In carrying its mandate to serve, it may find itself operating in a mode of survival instinct and had inadvertently overlooked normal peacetime procedure without any bad intention to undermine the law through expediency.

There had never been any stand-off between SAHPRA and the Military.  SAHPRA was allowed to enter into the unit by the Officer Commanding without any problem. SAHPRA had requested the Officer Commanding to open the store where the medicine was kept in order to satisfy themselves on storage conditions compliance.

Discussion

The Chairperson asked Mr Siphiwe Sokhela, Chief Financial Officer (CFO) of the  SANDF, if he was satisfied that the procurement steps had been taken?

Mr Sokhela responded that some of the processes had not been followed, but this was because of the nature of the pandemic and the way in which things were happening at the time.

Mr T Mmutle (ANC) said that the question asked by the Chairperson had not been properly answered, and he wanted clarity on the roles of those who were part of the procurement team.

Mr S Marais (DA) was of the view that it was important that the Committee should be told what the extent the transgressions were, and who had been part of those transgressions, because this information was important.

The Chairperson added that the Committee wanted to understand the supply chain of the SANDF, especially to know who had certain roles. He wanted to know if the CFO had delegated any person to authorise the procurement of the drugs.

The CFO responded that in terms of SANDF policy, procurement was under the logistics division and documents were checked to make sure that they matched with everything. A meeting had been held to get more details on what had really happened, and the logistics division was in a better position to provide more information.

The Chairperson asked the CFO if he was saying that he did not have a role in the procurement process.

The CFO responded that he was not part of the process, and did not play any role in the procurement.

Continuation of SANDF presentation

Maj. Gen. Joseph Tyhalisi, Project Thusano Director, SANDF, told the Committee that the South African and Cuban governments had a bilateral agreement on defence-to-defence relationships. These contracts had been signed by a duly appointed official. Subsequent to this agreement, Project Thusano had been born, which facilitated services that ought to be provided to both countries on specific professional and technical services required by each country. The South African Department of Defence had contract No. TI 17-001-SUDAFRICA to provide professional and technical services, and No. TI 17-002- SUDAFRICA to provide services of vocational training respectively with the Cuban Department of Defence.

The process of implementing activities and the implied military operational tasks, as outlined in the contracts, was firstly through a meeting by both parties to agree on the related military requirements of what needed to be achieved. Secondly, based on the principal agreement between both parties, a supplement would be drafted by both parties and it would be delivered to South Africa for verification, and after that, counter-signing would be done by a delegated official, and it was only then that the payment process would start.

The contract and supplementary agreements had to be signed in their original form, which implied that they must be delivered from one end to the other. As a result, the Cubans had to be the first signatories before the consignment left Cuba. The original signed documents had accompanied the consignment to RSA, and upon arrival the other party -- the Department of Defence -- had to sign them, which completed the legality of the documents and the consignment.

The regulation of Act 101 of 1965 Section 22, which directs the processes to be followed in importing pharmaceutical products, bears relevance. The SAMHS, as a subsidiary of government, perceived itself not in the same light as importing pharmaceutical companies and wholesalers, and in its judgment thought itself exempt in military-to-military agreements of biotechnology products such as Iinterferon. This was because the military had CBR sole capabilities in the country, and therefore perceived Force protection interferon as not a treatment, but a prophylactic biological product against a biological threat to internally deployed soldiers. This unfortunate error of judgment had been clarified with SAHPRA, and the ongoing inspection of integrity and use of medicines was being assured in line with legislation.

Emphasis was to be placed that there had been no need for the SANDF to embark on a procurement process to acquire this medical service because of its limited availability. South Africa’s bilateral agreement with Cuba had been useful to address the urgent requirement.

The Minister of Defence and Military Veterans had signed the terms of reference for the investigation, a copy of which had been forwarded to AGSA. Members of the Ministerial task team had already been appointed. What remained were administrative issues -- for example, oath taking and vetting.

The Chairperson thanked the SANDF for their presentation, and asked the representative from AGSA if they had received any documentation from the SANDF.

Mr Lourens van Vuuren, Business Executive, AGSA, confirmed that the entity had not yet received any information from the SANDF.

Discussion

Mr Marais said that he would like to get SAHPRA’s response to the presentation that had been made by the SANDF because of the contradictions between the two groups. He wanted to know if he was correct to assume that the drug purchased fell under schedule 5, 6 and 8 of section 22, and also section 29, together with 30, of the Medicines Act. He asked how big a clinical trial was. Was it a realistic trial and was it ideal to have it in the Defence Force? Mr Marais also wanted to know if the SANDF were subject to the rules and regulations of SAHPRA, because it sounded like they did not follow the rules of SAHPRA. He wanted to know if the drug was used without the authorisation of SAHPRA, and what SAHPRA did in cases of clear transgressions as had been done by the SANDF, to make sure that the drugs were not used without its approval.

Mr Marais asked whether the application for approval was supposed to be done before the importation, or if it could be done after the importation of drugs, because the first shipment arrived months before the application was made by the SANDF.

He wanted to find out if Col Mnisi was always present at the meetings where the decision was taken to import the drug into South Africa.

The Chairperson asked Mr Marais to give others a chance to ask questions, because there was not enough time.

Mr W Mafanya (EFF) wanted to know why SAHPRA did not act immediately, and what the consequences that followed were, because there had been a transgression to import the drugs into the country. He asked if SANDF had complied with the orders of SAHPRA. He said that South Africa was not a military state and the steps taken by the SANDF were not justifiable to import a drug for soldiers, because they were not the only frontline workers. He said that COVID-19 -19 was not a biological warfare, as stated by the SANDF, and he needed a better clarification from SANDF, because this showed that they did things on their own and they did not listen to advisors.

Ms M Modise (ANC) said that SAHPRA could have mentioned that there were a couple of attempts to meet with the colonel, and it had happened only a year later, so she wanted to know what had happened at the meeting. In terms of the bulk stock application, it was mentioned that no adequate information had been supplied, so what was it that the SANDF had not done for the drug to be used, because it meant that they had not supplied all the information required and this had led to the approval application being denied. She also asked if the SANDF had done an analysis on the importance of the drug, and if there were any soldiers who were affected by the administration of the drug. Thirdly, she wanted to know why SANDF was confident of the drug, because it was categorised as an immune booster and it did not prevent Covid-19. Was the SANDF aware that they were breaking the law, and had they considered the consequences of such actions?

Mr Mmutle wanted to know if the SANDF had not received approval from SAHPRA prior to the procurement of the drug. His second question was about Project Thusano, and if it had been delegated the powers to procure the drug because there had to be a person responsible for the process. The drugs procured were generally used by the SAHMS, and there was a grey area that was not being explained by SANDF. On the basis that the SANDF knew that approval was important, why had they acquired a lot of vaccines, because the drugs they procured were a lot in comparison to the numbers of SANDF members?

The Chairperson asked if it was possible to extend the meeting by an extra 30 minutes, since SAHPRA and the SANDF had not yet responded, and Members still had questions.

Mr M Shelembe (DA) was concerned about the essential services, because soldiers were not different from policemen and nurses. Why was it that the Department of Health had not attended the meeting that was held on the drug?

The Chairperson asked Mr Shelembe to ask questions that were directed to SANDF and SAHPRA, because the Department of Health was not present.

Mr Shelembe asked about the reason why the Department of Health did not attend the meeting, and if they were aware of such a meeting.

The Chairperson asked SAHPRA to respond to the questions that had been raised by the Members.

SAHPRA’s response

Prof Rees said that she was on a committee that had been dealing with producing medicines that were related to Covid-19, and she was also an advisor to the World Health Organisation (WHO). There had been extensive work done globally, and most of the drugs went through clinical trials. South Africa continued to be involved in the research for the drugs that would help prevent the spread of Covid-19, but there had been no desired results yet. Many of the drugs unfortunately had not proved to have the potential that was hoped for, and there was no evidence of prevention. The most important thing to do now was to go through clinical trials, and it did not help to roll out drugs that were not properly tested because it would lead to misleading people, and they could change their behaviour. It was important to have well structured clinical trials at this stage.

Dr Semete said that there had been an error in one of the slides, because it was supposed to be section 22, as it dealt with licensing.

She said that SAHPRA gave approval prior to the acquisition of drugs so that it knew and could assist if there were any challenges that arose. What SAHPRA had done when they became aware of the drug being in the country was to have a meeting, and had acted expeditiously. They did not go with the Hawks on the first visit, but only in January, as was the standard procedure of SAHPRA. It was important to sit down with Col May before opening a case against the SANDF, and the meeting scheduled for February had been cancelled. The drugs had been stored at 4 degrees, and SAHPRA had checked the temperatures to make sure that they were stored at the correct temperatures.

Mr Marais asked if 23 000 drugs was an adequate size for clinical a trial.

Prof Rees said the answer would depend on the end point that was being looked for. There were a couple of things to look at, because trials could have a few thousand, but it did depend on the end point. If it was an early disease, it meant that it would also be difficult to get results immediately.

The Chairperson asked SAHPRA about the remedies to be taken against the SANDF or what they were going to do, because three consignments of the drug had been procured, and they had not touched on that matter, even though they had dispatched their monitors to the SANDF’s premises.

Dr Semete said that it was unlawful to have a drug that was unregistered, and in many situations the facilities were inspected, and the product went through assessments to determine what they contained, and a detailed investigation would commence to determine what had led to the product being imported into the country. However, the current scenario was a different one, because meetings were scheduled with the SANDF.

The SANDF asked Dr Semete what this meant, because the meeting was not convened between the two parties.

Dr Semete responded that the drug had been stored under adequate conditions, although more tests were still to be done.

Mr Marais followed up on his question on whether the drugs fell under section 22, or if it was a drug that was not specified.

Dr Semete responded that section 22 dealt with different matters.

Mr Marais read section 22 to Dr Semete, since he felt she did not understand the question.

Dr Semete said that the Act would be applied if a product was imported without the required authorisation.

The Chairperson added that the Act would apply in this scenario, and released SAHPRA from the meeting.

Minister’s comments

Ms Nosiviwe Mapisa-Nqakula, Minister of Defence and Military Veterans, welcomed the interaction between SAHPRA and the SAMHS, because they had been talking past each other. She had raised her concerns at the National Coronavirus Command Council (NCCC) meeting to get a better understanding of the issue between the two parties, and Dr Rees had explained to her that SAHPRA had not registered interferon because trials at the WHO were at a low stage. The issue had been all over the media, and she had raised her concern over the quantities. She had not been aware of the drug being in the country, or even the name. A concern had been raised that the drug could not be administered to the soldiers only and not the family members that they stayed with, because it was an immune booster. She said categorically that interferon was not a vaccine, but an immune booster. The Minister was not comfortable with the idea of taking care only of the SANDF and had raised the matter with the NCCC, but had not received a direct response.

She was told that the drug had been cleared when she had asked if there was a possibility of smuggling the drug into the country, and was disappointed by some of the army generals because they had taken advantage of her. She was grateful that she had learnt a lot of lessons because of the pandemic, as it had exposed her to different procedures, but she had not been aware of the procurement of interferon.

The Chairperson asked the Minister what she was going to do, because the SANDF had broken the law by procuring the drug and did not take full responsibility, but blamed Col May.

The Minister responded that Col May held a junior rank and in the meeting there had been senior generals and colonels, and they should take responsibility instead of Col May. There had been interaction between the surgeon general and the office of the Minister of Health. The Minister also said that the issue of biological warfare had never been raised at the NCCC.

She said the SAMHS should continue to engage with SAHPRA until they reached common ground.

The Chairperson wanted to know what was going to happen to the officials who had not furnished the AGSA office with the information to finalise the audit, and those officials who were blocking SAHPRA access to the warehouse to conclude their investigations.

Ms Modise asked why the SANDF had not supplied SAHPRA with the documentation on their bulk application of the drug, and why had it not wanted to supply the information?

The Minister was of the view that the surgeon general should answer some of the questions, because she was not aware that the SANDF had not supplied SAHPRA and AGSA with the required documentation.  She had a responsibility to engage further with the generals to get a better understanding of what was going on. There was an investigation currently taking place, and it would investigate the matter of interferon amongst other matters.

The Chairperson thanked the Minister for her interaction with Committee Members.

Mr Mmutle suggested that the SANDF and the Committee should have another meeting.

The meeting was adjourned.