Transcript registration of medicines

REGISTRATION OF MEDICINES &
PROGRESS WITH RESTRUCTURING THE
MCC
1
OUTLINE
 Obligations & Functions
 Elements of effective regulation
 Requirements new medicines and generic
medicines
 Management of Clinical Trials
 Post registration amendments
 Pharmacovigilance & Post Marketing Surveillance
 Restructuring of the MCC
2
OBLIGATIONS
 Public safety & protection through ensuring efficacy,
safety & quality of medicines throughout their lifecycle
 Risk assessment – minimization of harm and
maximization of benefit
 Timely access to medicines & timely action on safety &
quality
 Transparency & accountability
 Responsiveness
 Capacity to regulate
3
ELEMENTS OF EFFECTIVE REGULATION
(WHO)
• Decisions should be based on scientific evidence
and facts
• Practicable enforcement capacity
• Accountability and public interest/public good
• Safeguard against conflict of interest
• Limit discretionary powers
• Good regulatory practices and standards
• Independence from public, commercial and
political pressure
4
FUNCTIONS
 Registration of medicines based on quality
efficacy and safety
 Management of post- marketing amendments
 Approval and monitoring of clinical trials
 Monitoring of safety
 Response to signals
 Licensing manufacturers, wholesalers and
distributors
 Provision of information
5
Medicines Control Council
& Expert Committees
Medicines Control Council
Chair Person
Medicines Control Council
Registrar of Medicines
Vice Chair Person
Pharmaceutical and
Analytical Committee
Biological Medicines
Committee
Names and Scheduling
Committee
Complementary Medicines
Committee
Clinical Trials Committee
Clinical Committee
African Traditional Medicines
Pharmacovigilance
Committee
Veterinary Clinical Committee
Bio-Therapeutic Committee
Legal Committee
6
REGISTRATION REQUIREMENTS OF
NEW CHEMICAL ENTITIES
 Development of a drug starts with the identification of potential




7
drug candidates (early research)
Preclinical Development - to determine the safety profile in
in vitro and in vivo animal studies
Toxicity studies include organs targeted by the drug
Any long term carcinogenic effects, toxic effects on mammalian
reproduction
Choice of animal species based on which one will give the best
correlation to human trials
REGISTRATION REQUIREMENTS OF
NEW ENTITIES cont.
Clinical trials
Phase I
 A sample size of 20 - 80 participants (usually healthy
individuals) to determine metabolic and pharmacological
actions and the maximally tolerated dose
 Factors to be identified: Bioavailability, dose proportionality,
metabolism, pharmacodynamics, pharmacokinetics
 Data focus: Vital signs, plasma and serum levels, adverse
events
 Duration: up to 1 month
8
REGISTRATION REQUIREMENTS OF
NEW CHEMICAL ENTITIES cont.
Phase II
 A sample size of 200 – 300 participants to evaluate effectiveness,
determine the short term side effects, identify common risks for a
specific population and disease
 Factors to be identified: Bioavailability, drug-disease interactions,
efficacy at different doses, pharmacodynamics, pharmacokinetics,
patient safety
 Data focus: Dose response & tolerance, adverse events, efficacy
 Design: Placebo controlled or active controlled comparisons
 Population: Individuals with target disease
 Well defined entry criteria & duration of several months
9
REGISTRATION REQUIREMENTS OF
NEW CHEMICAL ENTITIES cont.
Phase III
 To obtain additional information about the effectiveness of clinical
outcomes and evaluate overall risk-benefit ratio in a
demographically diverse sample
 Data focus: Laboratory data, efficacy, adverse events
 Factors to be identified: Drug - disease interactions, drug-drug
interactions, dosage intervals, risk benefit information, efficacy
and safety for sub-groups
 Design: Randomised, controlled, 2-3 treatment arms, broader
eligibility criteria
 Population: Individuals with target disease and hundreds to
thousands of participants
 Duration: Several years
10
REGISTRATION REQUIREMENTS OF
NEW CHEMICAL ENTITIES cont.
Phase IV (post-registration)
 Aim: to monitor ongoing safety in a large population
 Factors to be identified: Epidemiological data, efficacy and
safety within large diverse populations, pharmacoeconomics
 Data focus: Efficacy, pharmacoeconomics, epidemiology,
adverse events
 Design: Uncontrolled, observational
 Population: Individuals with target disease, new age groups,
genders etc.
 Risk management plans
11
GENERIC EVALUATION cont.
 Knowledge of composition of formulation
 Confirmation of chemical equivalence with innovator
drug
 Stability of formulation
 Proportional similarity of different strengths with
innovator comparator
 Derived from appropriately designed bioequivalence
protocols
12
QUALITY
 Quality – applies to all evaluations
 Active pharmaceutical ingredient , excipients,
impurities
 Manufacturing method
 Good Manufacturing Practice standards
 Specifications for the final product
 Container suitability
 Stability for shelf life determination
13
QUALITY PILLARS
Pre-registration
Pharmaceutical
assessment
GMP inspections
Validation
Qualification
Stability data
GCP inspections
14
Manufacturing Post Registration
Licence
GMP inspection
Responsible Pharmacist
GMP compliant
Natural Person
GMP certificates
CPP certificates
Recalls (Class, Type)
Advertising
QC testing
MANAGEMENT OF CLINICAL TRIALS
 No clinical trial may commence before approval by
both MCC and local Ethics Committee
 Local Ethics Committees registered with The
NATIONAL HEALTH RESEARCH COUNCIL
 Universal principles of autonomy, beneficence and
justice must be respected
 MCC has authority to terminate a clinical trial for
reasons of SAFETY or where there is evidence of GCP
violations
15
KEY ASPECTS FOR CLINICAL TRIAL
APPROVAL
In the approval of Clinical Trials the MCC considers the
following aspects:
a. Scientific rationale
b. Safety and
c. Contribution to new scientific knowledge
 Is it ethical, relevant and can patient safety be assured?
 When the trial is undertaken in South Africa the
subjects should benefit from the results of the research
KEY ASPECTS FOR CLINICAL TRIALS
cont.
SCIENTIFIC RATIONALE
 Does the trial contribute to new scientific knowledge?
 Is it plausible and scientifically appropriate?
 Is the study design optimal?
 Should the trial be conducted in the RSA?
 Is there adequate pre-clinical evidence of safety and
efficacy?
KEY ASPECTS FOR CLINICAL TRIALS
cont.
SAFETY
 Balance of risks versus benefits
 Is there adequate data from pre-clinical studies ?
 Are the animal models used appropriate?
 Is there adequate monitoring in place?
 Pharmacovigilance and GCP inspection reports
 Is safety stipulated as an objective?
POST MARKETING PHASE
 Safety monitoring
 Market surveillance
 Laboratory testing
 Good Manufacturing Practice compliance
 Good Clinical Practice compliance
 Variations and approval thereof e.g.
 Additional or new indications
 Change in source or method of synthesis of Active Pharmaceutical
Ingredient, excipients, packaging etc.
 Change of packer, laboratory release, packaging, address,
manufacturing site etc.
19
Applicants
Applicants
Dossier
Dossier
Regulatory Processes
Pre-marketing
Pre-marketingphase
phase
Post
PostMarketing
Marketingphase
phase
Market distribution
Licensing/Registration= evaluation process
Safety
Safety
monitoring
monitoring
Product
Product
Evaluation
Evaluation
Laboratory
Laboratory
testing
testing
Dossier
Dossier
Quality
Quality
Safety
Safety
Efficacy
Efficacy
Market
Market
surveillance
surveillance
Licensing
Licensing
facility
facility
GMP
GMP
compliance
compliance
Inspections
Inspections
Variations
Variations
Clinical
Clinicaltrials
trials
Approval
Approval
Ethics,
Ethics,GLP;GMP,GCP)
GLP;GMP,GCP)
Marketing
MarketingAuthorization
Authorization
Health Technology
and Pharmaceuticals
Technical Cooperation for Essential
Drugs and Traditional Medicine
PROGRESS
• Registration, rejections withdrawals
21
YEAR
TOTAL
08/09
541
09/10
748
10/11
970
11/12 Up to October
411
PROGRESS CLINICAL TRIALS
YEAR
2009
2010
2011
RECEIVED
212
202
254
APPROVED
205
181
154
WITHDRAWN
6
8
2
REJECTED
1
7
3
PENDING
0
6
93
NOTIFICATION
22
2
RESTRUCTURING OF THE MCC
 Three sets of regulations have been published for public comment
 Complementary and Alternative Medicines
 Medical Devices and In Vitro diagnostics
 Food
 Legislation however must be amended to:
 Separate medicines from the definition of health products to
avoid blurring the classification of medicines with the
classification of devices
 Enable the regulation of food and cosmetics
 Strengthen governance issues in the statute
 Strengthen some elements medical device regulation in the
statute
23