MCC presentation to Portfolio Committee on Health

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MCC presentation to Portfolio Committee on Health

• -Dr T M Mathivha
• Vice-Chair MCC
• Friday 16 August 2002

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MEDICINES CONTROL COUNCIL

• Medicines and Related Substances Control Act,
  (Act 101 of 1965)
• Sect 2(1) Establishment, Powers and Functions of
  MCC
• Sect 2(2) Council may advise the Minister or
  furnish a report to the Minister on any matter
  referred to the Council by the Minister for
  consideration and arising from the application of
  this Act
• Sect 3(2) Appointment of Council members by the
  Minister
• Sect 9 Council appoints executive committee and
  other committee members

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MEDICINES CONTROL COUNCIL

• Responsibility for approving medicines for
  use in South Africa and the control thereof
• Sect 1(3) In determining whether or not the
  registration or availability of a medicine is in
  the public interest, regard shall be had only to
  the safety, quality and therapeutic efficacy
  thereof in relation to its effect on the health
  of man or any animal, as the case may be

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MEDICINES CONTROL COUNCIL

• 24 Council members with well defined
  expertise and skills
• 10 Technical Expert Committees
• 146 members in total
• Academic, research and professional backgrounds
• Various institutions throughout the country
• Range of skills and expertise to the regulatory
  process

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MEDICINES CONTROL COUNCILEXPERTISE

• Experts in the fields of clinical immunology,
  clinical pharmacology, virology, toxicology,
  epidemiology, biochemistry, biostatistics,
  pharmaceutics, pharmaceutical and analytical
  chemistry, as well as experts in all specialties
  of clinical medicine, dentistry, pharmaceutical
  and veterinary sciences and complementary health

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COMMITTEES OF COUNCIL

1. Clinical Committee
2. Pharmaceutical and Analytical Committee
3. Clinical Trials Committee
4. Biologicals Committee
5. Veterinary Committee
6. Scheduling Committee
7. Complementary Medicines Committee
8. African Traditional Medicines Committee
9. Pharmacovigilance Committee
10. Veterinary Clinical Committee

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Registrar of Medicines

• Sect 12(1) Registrar of Medicines appointed by
  the Minister after consultation with Council
• Statutory functions imposed under the Act
• Secretariat to Council
• Issues certificates of registration for medicines
  approved by Council

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Administration and Technical Support to MCC

• Provided by the Office of the Registrar of
  Medicines
• A staff complement of 102 with pharmaceutical,
  clinical, scientific and administrative knowledge
  and experience.
• Central activities in Pretoria
• Two safety monitoring units at MEDUNSA and UCT

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History of Medicine Regulation in South Africa

• South Africa was among the first countries in the
  world to introduce specific legislation to
  regulate medicines
• Began more than 30 years ago with the Thalidomide
  disaster in the early 1960s
• Over 200 Council meetings have been held since
  its inception and approximately 20 000 medicines,
  including antiretroviral, have been approved to
  date

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History of Medicine Regulation in South Africa

• Evaluation, approval and registration of medicine
  for sale in South Africa occurs through expert
  opinion and peer-review processes of the
  technical committees of Council
• 17 antiretroviral agents have been approved by
  the MCC through these technical processes
• Recognition of the regulatory decisions of
  established regulatory agencies of other
  countries, namely, USA, UK, Australia, European
  Union.

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MEDICINES CONTROL COUNCIL International
Co-operation

• Since 1979, member of Pharmaceutical Evaluation
  Review group an international forum for
  established regulatory agencies
• Also served as chair to this body
• Membership and involvement enables exchange of
  evaluation reports on safety and efficacy of
  medicines with various regulatory agencies
  including the the Medicines Control Agency (UK),
  the Therapeutic Goods Administration (Australia)
  Sweden
• Regulatory exchanges are also regularly
  undertaken with the US Food and Drug
  Administration (FDA)

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DRUG SAFETY

• Continuous and routine reviews of status of all
  registered medicines
• Basis national and international reporting of
  adverse drug reactions (ADRs)
• Legal requirement reports of ADRs of any
  medicine approved by Council submitted timeously
  to MCC
• If cause for alarm -registration of the medicine
  reviewed and if necessary de-registered and
  withdrawn from the market

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PHARMACOVIGILANCE UNIT - ANTIRETROVIRAL AGENTS

• A new Pharmacovigilance Unit established at the
  Medical University of South Africa (MEDUNSA).
• Primary function - to monitor adverse events
  related to antiretroviral therapy in South Africa
• Works in collaboration with the existing MCC
  Pharmacovigilance Unit based at the University of
  Cape Town

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PHARMACOVIGILANCE UNIT - ANTIRETROVIRAL AGENTS
(2)

• Already embarked on a survey of the pilot sites
  where nevirapine is being used to reduce mother
  to child transmission of HIV.
• Other programmes - focus attention on safety
  monitoring during the conduct of clinical trials
  with antiretroviral agents.

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Drug Registration Process

• PRE CLINICAL STUDIES
• Elucidate hazards estimate risks
• CLINICAL
• Data from Clinical Trials
• Pivotal study (unequivocal evidence, clinical
  expert report, appropriate diagnostic outcome
  criteria, general applicability)

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REGISTRATION STATUS IN OTHER COUNTRIES

• Detail approvals with indications, deferment,
  withdrawal,rejection with reasons
• Year of approval and conditions, formulations,
  indications, dosages, copy of PI registration
  certificate or particulars
• KEY COUNTRIES
• MCA OF UK
• FDA OF USA
• TPP OF CANADA
• TGA OF AUSTRALIA
• EMEA OF EU

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Drug Registration Quality

• Manufacturing Procedures
• Site master file
• Inspection flow diagram
• GMP WHO type certificate
• In process controls
• STABILITY PROGRAM
• temperature, humidity
• time points of determination
• FINAL PRODUCT SPECIFICATIONS
• Identification(salts, isomers)
• Assays
• Dissolution profile

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NEVIRAPINE (NVP)RECORD OF EVENTS AND REGULATORY
DECISIONS

• 1996 Submission of application to register
  nevirapine (NVP) - use with other antiretroviral
  agents for the treatment of chronic HIV infection
  was first filed with the MCC.
• 1998 February Indication approved, product
  registered. Subsequently several changes made to
  package insert of product to address new
  information on its safety and efficacy, in line
  with international regulatory decisions.

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• 1999 August WHO Technical Meeting on nevirapine
• 1999 November Application received to fast track
  the approval of nevirapine as a single agent
  (monotherapy) for the reduction of HIV
  transmission from mother to child(MTCT), based on
  a single study conducted in Uganda (HIVNET012).
• 2000 January Clinical Committee of the MCC
  presented its recommendations for Fast Track
  Approval to Council.
• 2000 March Report of Resistance concerns by the
  World Health Organisation on the HIVNET012 study.
• 2000 April At this stage, Council deferred its
  decision due to limited evidence of safety and
  efficacy, concerns of resistance and since an
  ongoing study (SAINT study) with NVP for this
  indication was being conducted in South Africa
• 2000 April Decision on the applicants request
  for the inclusion of the claim for the prevention
  of MTCT be deferred until further clarification
  on reported Resistance and results of the Saint
  Study at end on July 2000 is available

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• 2000 July Post AIDS 2000 Conference, special
  committee of council established to assess the
  pronouncement at conference and data submitted,
  and published data on, safety, efficacy,
  resistance, breastfeeding.
• 2000 August Council requested meeting with
  researchers and the manufacturer of nevirapine
• - discuss NVP and SAINT Study
• - request full data and report from SAINT study
• 2000 September further meetings of the technical
  committees of council on NVP for MTCT. Resolved
  that Council is treating the matter with the
  urgency it affords by requesting the Clinical
  committee to hold an extra-ordinary meeting and
  Council to have a two day meeting in October in
  order for Council to apply their minds and to
  debate the issue properly
• 2000 October Council decision - refer matter to
  clinical committee for decision on safety

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• 2000 November First Council resolution on NVP
  for MTCT(see handout-A)
• 2000 December Executive Committee of Council
  meeting
• 2001 February Further resolutions on NVP(see
  handout-B)
• 2001 March- final resolution of MCC with
  conditions(see handout-C)
• 2001 April final package insert and clarity on
  lack of efficacy
• APPROVAL FOR THE INDICATION FOR MTCT
• 2001July Due date for submission of SAINT report
  by manufacturer
• 2001 October Reminder to manufacturer to submit
  SAINT study report and 6 monthly safety report
• 2001 November SAINT study report submitted to
  council by manufacturer
• 2001 December Review of report by clinical trial
  committee

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• 2002 January MCC discuss SAINT study report
• 2002 March- letter from manufacturer - problems
  in Uganda
• EXCO had a special meeting, letter to Minister
  and copy to DG informing him in terms of Section
  2 of the Act
• 2002April letters to manufacturer, FDA, NIH on
  HIVNET 012
• 2002 April response from FDA and manufacturer
• 2002 April 26 Special meeting of Council to
  Discuss Nevirapine
• 2002 May further response to manufacturer, FDA
  and NIH,
• 2002 May 10 MCC meeting Further discussion on the
  reports
• 2002 June Correspondence from manufacturer, NIH
  and MCC response to NIH.

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• June 7 Exco Meeting Further discussion and
  review of the data and information supplied and
  decision to invite the applicant to next Council
  meeting in July 2002
• 2002 July Meeting with US official (Health
  attaché of the US embassy) in MCC offices .
  Discussion on the conditions in which we can
  obtain the data from NIH.To sign confidentiality
  but can only view the data at the US embassy and
  not obtain a hard copy! Also informed that a
• re-monitoring of the HIVNET012 site at a
  significant cost and the results will be
  available in September 2002
• 2002 July Meeting with manufacturer at July
  Council meeting.