Transcript MEDICINES CONTROL COUNCIL

MCC presentation to Portfolio
Committee on Health
-Dr T M Mathivha
Vice-Chair MCC
Friday 16 August 2002
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
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”
MEDICINES CONTROL COUNCIL
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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
MEDICINES CONTROL COUNCIL
EXPERTISE
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
COMMITTEES OF COUNCIL
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Clinical Committee
Pharmaceutical and Analytical Committee
Clinical Trials Committee
Biologicals Committee
Veterinary Committee
Scheduling Committee
Complementary Medicines Committee
African Traditional Medicines Committee
Pharmacovigilance Committee
Veterinary Clinical Committee
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
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
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 1960’s
 Over 200 Council meetings have been held since
its inception and approximately 20 000
medicines, including antiretroviral, have been
approved to date
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.
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)
DRUG SAFETY
Continuous and routine reviews of status of all
registered medicines
Basis – national and international reporting of
adverse drug reactions (ADR’s)
Legal requirement – reports of ADR’s 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
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
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.
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)
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
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MCA OF UK
FDA OF USA
TPP OF CANADA
TGA OF AUSTRALIA
EMEA OF EU
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
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.
 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
 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
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- discuss NVP and SAINT Study
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- 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
 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
 2002 January: MCC discuss SAINT study report
 2002 March- letter from manufacturer - problems in Uganda
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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.
 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.