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Supporting Affidavit to the First to Ninth Respondents’ Answering Affidavit
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I, the undersigned
PHILIP CHUKWUKA ONYEBUJOH
do hereby make oath and say:

1.	I am a medical practitioner registered with the Health Professions Council of South Africa in the capacity of a medical officer in the public sector.  My qualifications are as follows:  I have a Bachelor of Medicine and a Bachelor of Surgery degree (MB, BS).  I continued with postgraduate training in medicine which culminated in the award of a MSc in Clinical Tropical Medicine (infectious diseases), a diploma in Public Health and Tropical Medicine (Royal College of Physicians) and a PhD in Clinical Immunology of Infectious Diseases all from the University of London.  I am currently on leave of absence from the Medical Research Council in the capacity of Director Clinical, Biomedical and Experimental TB research.  I am also a fellow of the South African Academy of Sciences.  My current position is, ProTEST Task Manager, Stop TB department, TB strategy and operations, WHO Geneva.  This affidavit is deposed to in my capacity as a member of the Medicines Control Council of South Africa (MCC), and on the basis of my qualifications as they appear in my curriculum vitae.  The opinions expressed herein have been made in my personal capacity and as a member of the MCC, and do not reflect any endorsement by the World Health Organisation (WHO) that currently employs me.  I annex hereto, a copy of my curriculum vitae, marked “PO1” and pray that it be read as if specifically incorporated herein.

2.	The facts deposed to herein are based on my personal knowledge and are true and correct.  To the extent that I have relied on information and advice provided to me by other parties, their confirmatory affidavits are filed herewith.

3.	
3.1	This affidavit is part of the response of the First to Ninth Respondents.  I deny the averments or conclusions contained in the Applicants’ papers which are inconsistent with what I say in this affidavit.

3.2	In my capacity as a member of the MCC, I have the written authority of the Director-General of Health, Dr Ayanda Ntsaluba (Ntsaluba) to disclose such information as was acquired by me in the exercise of my powers and performance of my functions in terms of the Medicines and Related Substances Control Act No 101 of 1965.

4.	I have had extensive clinical experience in the management of infectious diseases and in the conduct and management of clinical trials aimed at evaluating investigational new drug applications within the platform of Good Clinical Practice (GCP).  In this regard, I have managed and investigated HIV positive patients with different opportunistic infections.  I have been involved in HIV/AIDS research from 1989 whilst gathering data for my PhD in Clinical Immunology.  My experience in evaluating new interventions among HIV/AIDS patients and in investigating the determinants of the immunopathology of HI, justifies the opinion stated here.  Furthermore, as a member of the MCC and the head of the special panel convened by the MCC to look at the information submitted by the applicants for the registration of Nevirapine for the indication of prevention of intrapartum transmission of HIV from mother to child, I consider myself eminently qualified to shed more light on the deliberations that informed the registration of Nevirapine for the stated indication and the other opinions I express herein.

Registration of Nevirapine
5.	The increasing HIV pandemic has informed the need to develop new interventions aimed at decreasing transmission of HIV.  Prime among these interventions is the prevention of MTCT of HIV to impact on childhood disease.

6.	Nevirapine, a non-nucleoside reverse transcriptase inhibitor with potent antiretroviral activity, rapidly absorbed orally and with efficient transplacental passage has been identified as a candidate for use as a single intervention for the prevention of mother-to-child transmission (PMTCT).  The safety and efficacy of a single does of Nevirapine given orally at the onset of labour and to neonates during the first week of life compared with AZT given similarly was evaluated in Kampala Uganda (HIVNET 012).

7.	The MCC considered registration of Nevirapine based on the data from HIVNET 012 and decided to conditionally register Nevirapine, for the prevention of intrapartum transmission of the HIV-1 from mother-to-child.  The conditional registration was done to facilitate the acquisition of long-term safety data and investigate the impact of resistant isolates on the overall efficacy of the intervention.  To achieve this and to reflect accurately the scientific information regarding HIV transmission it was also stated by the MCC that breastfeeding should be a contraindication.  A reference to the programmatic context in which Nevirapine should be prescribed for the registered indication was also indicated as a requirement by MCC.

8.	The need to conditionally register Nevirapine was informed by the following:

8.1	registration data was obtained from only one clinical trial conducted in Uganda;

8.2	the need for more information regarding safety, efficacy and resistance; and

8.3	the possible impact of ecological differences on the overall public health impact of the intervention on HIV transmission vertically.

9.	Although normally, data from multi-centre clinical trials are utilised in registration of new products, the MCC considered that, in the public interest, data from a single clinical site could be utilised in registering Nevirapine for the indication applied for.  However, as this was with insufficient information, it was deemed appropriate to request the applicants to submit data that would further support the available information on Nevirapine.

10.	The reason for the non-utilisation of the SAINT study, which was a prospective randomised open-label clinical trial to determine the efficacy of Nevirapine compared with ZDV + 3TC in decreasing peripartum transmission of HIV, for the registration of Nevirapine, has been addressed in Dr J Levin’s (Levin) affidavit.  Levin who apart from serving on the panel is also a member of the MCC’s Clinical Trials Committee.  Briefly, the panel evaluated the data submitted by the SAINT study and found that inadequate design impeded the validation of the efficacy of Nevirapine for the stated indication.  To adequately meet the MCC’s requirements, the following stipulations were made:

10.1	The MCC recommended the appropriate documentation and reporting of any adverse event, particularly serious adverse events and the reporting of any evidence of lack of efficacy from the cohorts of individuals utilising Nevirapine for the indications registered.

10.2	A number of studies have indicated the potential for breastfeeding practices to reverse initial gains of antiretroviral interventions preventing mother-to-child transmission of HIV.  In the light of this, the MCC considered the special precaution of indicating that breastfeeding might alter the efficacy and effectiveness of Nevirapine for the indication registered.  It was thus decided that the package insert should reflect this knowledge and thus prospective mothers who are about to receive the intervention would be made aware of the impact of infant feeding practices on the efficacy of Nevirapine.

10.3	A 6-monthly report was requested from the applicants as a condition for registration.

11.	The applicants allege that the MCC registration of Nevirapine for use to reduce the risk of MTCT of HIV is an indication that Nevirapine has authoritatively been found suitable for this purpose and that it is safe and is qualitatively and therapeutically efficacious.  This is an oversimplification of the process of registration.  The MCC considers the registration of an intervention for a mentioned indication on grounds of quality, safety, efficacy and in the public interest.  Whilst the process of registration rigorously investigates the claims of an applicant for registration of a new chemical entity in respect of quality, safety and efficacy, the public health is also considered.  This would mean that if the MCC is reasonably satisfied with the current safety and efficacy data of a product and the potential public health impact is considered to be great, provisional or conditional registration may be granted, with the requirement for further supporting data to monitor safety, quality and efficacy.  Thus, the magnitude and public health impact of HIV is a good example of the need to facilitate an intervention in the public sector with potential to decrease the disease burden.  This approach is consistent with the accelerated process of approval of antiretroviral drugs, which is usually accompanied by conditions including post-registration monitoring and reporting to the MCC adverse drug reactions.  This approach has also been utilised by other regulatory authorities both in the United States of America and the European Union.  This would imply that the registration process does not confer permanent safety and effectiveness on a product to the extent that it can be used by a healthcare provider without encountering any problems.  In the European Union, the European Medicinal Evaluation Agency’s (EMEA) approach is to utilise softer clinical endpoints with respect to quality and quantity of evidence, that is minimal evidence.  The proviso for registration in such instances would be for stringent conditions to govern the post marketing confirmatory data to be supplied by the applicant.  The applicants for the registration of Nevirapine were thus charged with the responsibility of providing data on resistance to Nevirapine and to report on the findings of the ongoing SAINT trial.  Thus, the registration of Nevirapine for the indications applied for was granted more in response to the public health imperative of providing an intervention to decrease vertical transmission of HIV.  However, taking cognisance of the need to optimise efficacy, safety and quality of Nevirapine, the MCC instructed the applicants to provide such data on an ongoing basis, thus ensuring that these attributes are not compromised by the registration process adopted.  To assume that the process adopted gives blanket approval with regard to quality, safety and efficacy as suggested by the applicants would be incorrect and misleading with regard to drug regulatory approvals.

12.	I annex hereto copies of the resolutions of the MCC for 24th November 2000, marked “PO2”, 15th February 2001, marked “PO3” and 30th-31st March 2001, marked “PO4”.