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General Principles of Medicines Regulation
Dr Lembit RägoCoordinator
Quality Assurance and Safety: Medicines (QSM)Medicines Policy and Standards (PSM)
WHO Headquarters, Geneva, [email protected]
Meeting on WHO Prequalification Programme on Priority Essential Medicines, WHO/EMRO
6-7 June 2007, Cairo, EGYPT
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Topics
Innovative and generic medicines Product information Structure of the dossier of medicinal products
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
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
SmellAppearance Taste
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Why medicines are special category of products?
Consumers, patients and health care workers have limited capacity to judge there
SAFETY QUALITY EFFICACY
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Are all medicines safe, effective and meet quality criteria?
No, they are not, and no they do not
Some are safe, but not effective or necessarily meet the quality criteria
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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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Quality - Safety
Some safety parameters are determined by quality
Some safety parameters are determined by the intrinsic properties of active pharmaceutical ingredient
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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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
What type of medicines we have?
Originator products
Multisource (generic) products
KEY – INTERCHANGEABILITY, more important THERAPEUTIC INTERCHNGEABILITY
ALL LITERATURE IS BASED ON ORGINATORS
No interchangeability – NEED FOR NEW SAFETY and EFFICACY DATA, NEW BOOKS HAVE TO BE WRITTEN
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
What type of regulations exist and how they differ?
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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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Generics and not generics
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 drug2. be identical in strength, dosage form, and route of
administration3. have the same use indications 4. meet the same batch requirements for identity ,
strength, purity and quality5. be manufactured under the same strict standards of
GMP required for innovator products.6. be bio-equivalent
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Generic drugs
In case of safety and efficacy the only way is to refer to originator product Thus the efficacy (indications, dosing) and safety information (side
effects, warnings etc.) can not be different But are they?
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Regulations: Global vs National
National regulations still differ a lot – especially for generics
What is ICH and what it is not?
Regional harmonization initiatives
Do global norms exist for generics?
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Who sets the standards?Is the WHO Involved?
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;
Example of WHO work from 1966
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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
Good Regulatory Practice : 9th ICDRA 29/4/1999
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Intrinsic safety issues (NOT quality related)
Not a single drug is completely safe! Predictable and preventable ADRs/ADEs New, unpredictable and unpreventable ADRs
New concepts - safety through whole life cycle of a drug 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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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Completely safe medicines are a myth: low dose aspirin case
Usefulness of low dose aspirin (75-325 mg) in secondary prevention of thrombotic cardiovascular or cerebrovascular disease proven
In many countries it is also approved for primary prevention of vascular events of coronary heart disease (US FDA has approved only secondary prevention).
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
If NO DISEASE low dose aspirin can increase a risk to die (from hemorrhagic stroke) …
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
How big is a problem?
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).
RATIONAL USE is a key to avoid ADRs that are predictable and avoidable
Important role of INFORMATION
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Specific reviews of medicinesSpecific reviews of medicines
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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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Two different regulatory approaches to medicines information: Australian example
Therapeutic Goods Regulations 1990 (compliant 1 October 2004) Schedules 12 and 13 for prescription and pharmacy only products Content based regulation whereby a list of required information is
prescribed Therapeutic Goods Roder 69A for non-prescription and
complementary products Performance based regulation whereby regulation identifies the
tasks that consumers ought to be able to carry out using the information
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
Conclusions on iformation
Medicine = tablet + information Good quality drug information including PILs is a shared
responsibility of industry and regulators 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
Not only accuracy of information but also its proper communication is important
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Department of Medicines Policy and Standards, Health Technology and Pharmaceuticals
…and realities
In many countries do not have enough resources to check information or approve SPCs and PIL
In some countries prescription only medicines do not have PIL (OTC medicines have) …but can be obtained without any prescription
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
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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