Transcript Department of Medicines Policy and Standards, Health Technology

General Principles of Medicines
Regulation
Meeting on WHO Prequalification Programme on Priority
Essential Medicines, WHO/EMRO
6-7 June 2007, Cairo, EGYPT
Dr Lembit Rägo
Coordinator
Quality Assurance and Safety: Medicines (QSM)
Medicines Policy and Standards (PSM)
WHO Headquarters, Geneva, Switzerland
[email protected]
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Topics
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Innovative and generic medicines
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Product information
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Structure of the dossier of medicinal products
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Usual perceptions may not help to make judgments
about medicines …and even pharmacists and medical
doctors may not be in capacity of taking decisions
without specific training
Appearance
Smell
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Taste
Why medicines are special category of
products?
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Consumers, patients and health care workers have limited
capacity to judge there
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SAFETY
QUALITY
EFFICACY
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Are all medicines safe, effective and meet
quality criteria?
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No, they are not, and no they do not
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Some are safe, but not effective or necessarily meet the
quality criteria
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Some may be effective, meet quality criteria but are not
safe
Some meet quality criteria but are not necessarily safe or
have any efficacy
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Quality - Safety
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Some safety parameters are determined by quality
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Some safety parameters are determined by the intrinsic
properties of active pharmaceutical ingredient
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However, in fact QUALITY in general perception (and
often in policy documents) is incorporating also
expectations for efficacy and safety without necessarily
saying so
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What type of medicines we have?
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Originator products
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Multisource (generic) products
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KEY – INTERCHANGEABILITY, more important
THERAPEUTIC INTERCHNGEABILITY
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ALL LITERATURE IS BASED ON ORGINATORS
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No interchangeability – NEED FOR NEW SAFETY and
EFFICACY DATA, NEW BOOKS HAVE TO BE
WRITTEN
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What type of regulations exist and how they
differ?
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For innovator products proof of QUALITY, SAFETY and
EFFICACY is needed
For multisource products QUALITY, safety and efficacy
data is referred to the originator, providing only evidence
about interchangeability (bioequivalence, clinical testing,
in certain cases dissolution data)
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Generics and not generics
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FDA requirements for generic drugs
(www.fda.gov/cder/ogd)
Generic drugs must:
1. contain the same active ingredients as the innovator
drugs as the innovator drug
2. be identical in strength, dosage form, and route of
administration
3. have the same use indications
4. meet the same batch requirements for identity ,
strength, purity and quality
5. be manufactured under the same strict standards of
GMP required for innovator products.
6. be bio-equivalent
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Generic drugs
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In case of safety and efficacy the only way is to refer to
originator product
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Thus the efficacy (indications, dosing) and safety information (side
effects, warnings etc.) can not be different
But are they?
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Regulations: Global vs National
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National regulations still differ a lot – especially for
generics
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What is ICH and what it is not?
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Regional harmonization initiatives
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Do global norms exist for generics?
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Who sets the standards?
Is the WHO Involved?
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WHO has the unique mandate to set
standards
WHO Constitution (Chapter II, Article
2), inter alia, states (6):
 In order to achieve its objective, the
functions of the organization shall be:
… to develop, establish and promote
international standards with respect to
food, biological, pharmaceutical and
similar products;
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Example of WHO
work from 1966
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Good Regulatory Practice : 9th ICDRA
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29/4/1999
Mission and objectives clearly stated
Possibility to assess attainment of objectives
Procedures and outcomes transparent to applicants, health
professionals, and public
Arguments used to reach decision accessible to the public
Reasonable duration of assessment without compromising
quality, safety & efficacy
Expedite review for orphan and outstanding public-health-value
drugs
Accountability to government, those regulated, and the public
Personnel adequately trained, highly qualified, of high integrity
Human resource development programme
Mechanisms for appeal and for citizens' complaints
Access to appropriate knowledge and technology
Citizens are provided with accurate and appropriate drug
information
Mechanisms to ensure quality of operating procedures
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Intrinsic safety issues (NOT quality
related)
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Not a single drug is completely safe!
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Predictable and preventable ADRs/ADEs
New, unpredictable and unpreventable ADRs
New concepts - safety through whole life cycle of a drug
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Preclinical testing
First in man trials
Clinical trials to prove efficacy (pre-marketing)
Post-marketing activities for gathering new data (Phase IV trials,
prosepective pharmacovigilance planning, targeted monitoring etc)
ADR reports and data analysis
Constant improving of INFORMATION on medicine and
communication
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Completely safe medicines are a myth:
low dose aspirin case
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Usefulness of low dose aspirin (75-325 mg) in secondary
prevention of thrombotic cardiovascular or cerebrovascular
disease proven
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In many countries it is also approved for primary prevention of
vascular events of coronary heart disease (US FDA has approved
only secondary prevention).
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Usefulness and efficacy is ALWAYS balanced against the risk – the
higher the risks the higher risks in terms of safety we may wish to
take
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If NO DISEASE low dose aspirin can increase a risk to die (from
hemorrhagic stroke) …
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How big is a problem?
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A recent US study estimated that 106 000 patients die and 2.2
million are injured each year by adverse reactions to prescribed
drugs (Lazarou et al, 1998).
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RATIONAL USE is a key to avoid ADRs that are predictable and
avoidable
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Important role of INFORMATION
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Specific reviews of medicines
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Review of Kava
Pharmacovigilance for
antiretrovirals
Amodiaquine + artemisinin
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Correct information and its proper
communication can reduce (preventable) ADRs

27th Annual Meeting of Representatives of the National Centres
participating in the WHO Programme for International Drug
Monitoring
Dublin, Ireland, 4 - 6 October 2004
 The summary of product characteristics (SPC) could be an
effective tool in preventing ADRs. Accurate and recent information
should be provided in the SPCs. The SPC should be appropriately
worded and presented to help health professionals get the
summary quickly and with the least effort. Doctors should be
advised to read all package inserts and labels.
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Two different regulatory approaches to
medicines information: Australian example
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Therapeutic Goods Regulations 1990 (compliant 1 October
2004) Schedules 12 and 13 for prescription and pharmacy
only products
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Content based regulation whereby a list of required information is
prescribed
Therapeutic Goods Roder 69A for non-prescription and
complementary products
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Performance based regulation whereby regulation identifies the
tasks that consumers ought to be able to carry out using the
information
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Conclusions on iformation
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Medicine = tablet + information
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Good quality drug information including PILs is a shared
responsibility of industry and regulators
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Regulators with limited resources could do more for public
health by trusting scientific assessments by well
resourced DRAs and concentrating more on ensuring the
accuracy of drug information in national settings
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Not only accuracy of information but also its proper
communication is important
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…and realities
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In many countries do not have enough resources to check
information or approve SPCs and PIL
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In some countries prescription only medicines do not have
PIL (OTC medicines have) …but can be obtained without
any prescription
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Most of the World population has only one prescription for
all medicines – banknote. Can this give them also the
information they need and understand?
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Realities…
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Structure of the dossier
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Would it be harmonised a lot of resources would be
saved
 Industries would have one dossier structure for different
submissions
 Regulators could communicate better
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