WHO Essential Drugs Strategy - PowerPoint PPT Presentation

1 / 56
About This Presentation
Title:

WHO Essential Drugs Strategy

Description:

Title: WHO Essential Drugs Strategy Author: WHO Drug Action Programme Last modified by: ragol Created Date: 3/12/1997 10:59:12 AM Document presentation format – PowerPoint PPT presentation

Number of Views:311
Avg rating:3.0/5.0
Slides: 57
Provided by: WHODrugAc46
Category:

less

Transcript and Presenter's Notes

Title: WHO Essential Drugs Strategy


1
Global Review of Medicines Regulation Current
Highlights and Future Trends
National Regulatory Conference 2005 Kuala
Lumpur, Malaysia 6 September 2005
Dr Lembit Rägo Coordinator, Quality Assurance
and Safety Medicines Medicines Policy and
Standards World Health Organization E-mail
ragol_at_who.int
2
Content
  • Introductory remarks
  • Global regulatory environment
  • Harmonization
  • New challenges and trends
  • Role of WHO
  • Challenges remaining

3
Medicines regulation What is it all about?
Taste
Smell
Appearance
Usual perceptions may not help in making
judgements about medicines
4
Why Stringent Standards for Medicines?
  • Medicines are different from other goods as
    patients (consumers) and even health care
    professionals are not able to judge their
    "quality" or "fitness for use"
  • " drugs are a public good and not simply just
    another commodity first for their high social
    value, and then because consumers and prescribers
    are unable to assess their quality, safety and
    efficacy" (Dr Gro Harlem Brundtland, former
    Director General of the World Health
    Organization)
  • This is the reason why medicines belong to one of
    the most regulated group of products

5
What Standards for Medicines?
  • Medicines must meet quality, safety and efficacy
    criteria.
  • These three sets of requirements are
    complementary to each other and each product has
    to be of good quality, safe and efficacious.
  • It is possible that a product is of good quality,
    but may not necessarily be effective or safe
  • It is possible that a product is effective, but
    may not necessarily be of good quality or safe
  • It is possible that a product is safe but may not
    be of good quality or effective

6
What type of medicines we have? 1. Innovator
products
  • For these products one has to prove their safety,
    efficacy and quality. Basis for these criteria is
    created by respective scientific disciplines.
    Implementation is executed through respective
    laws and regulations.
  • Proving safety and efficacy is the key for these
    products. It is based on the results of
    pre-clinical (i.e. animal toxicology) and
    clinical (clinical studies carried out in healthy
    volunteers and patients) research
  • Innovator (or originator) products
  • New innovative products that nobody yet has
    marketed, usually based on the new active
    ingredient (chemical compound which is
    responsible for its effects in human subjects)
  • The manufacturer has also to prove that its
    processes to produce the product and methods
    invented to control its quality are meeting
    established quality requirements.

7
Who sets the scene for regulating innovator
products?
8
International Conference on Harmonisation of
Technical Requirements for Registration of
Pharmaceuticals for Human Use Six Co-sponsors -
members of Steering Committee European
Commission EC European Federation of
Pharmaceutical Industry Associations EFPIA J
apanese Ministry of Health and Welfare MHW Japa
nese Pharmaceutical Manufacturers
Association JPMA US Food and Drug
Administration FDA Pharmaceutical Manufacturers
Association PhRMA
9
ICH Steering Committee Observers
  • World Health Organization (WHO)
  • Canada - Health Protection Branch
  • European Free Trade Area (EFTA)

10
ICH SC latest press release 2005
11
ICH Global Cooperation Group (GCG)
12
ICH Global Cooperation Group (GCG) - challenges
  • Very different by composition (countries with
    very different level of socioeconomic
    development) and objectives regional
    harmonization initiatives
  • Often in some countries indirectly involved ABC
    not yet fixed whereas other countries may have
    much higher levels of development
  • Relatively low level of resource investments
    available in harmonization as compared to ICH
  • Some may more have interest in regulating generic
    medicines well first (but this is not exactly ICH
    objective)

13
How can non-ICH countries benefit from ICH
products? Challenges for policy makers
  • Priority setting (ABC first) may be long way to
    go
  • Real control of market, functional DRA and
    inspectorate
  • Basic quality assurance measures like GMP, etc.
  • If market 90 generics, regulate well generics
    first
  • Implementation of ICH products vs recognition of
    registrations based on ICH guidelines?
  • Availability of resources
  • What is the cost of implementation of ICH
    guidelines and training?
  • What is the minimum number of regulators needed
    to assess a new drug according to ICH guidelines
  • Step-by-step approach

14
Where are we going with innovation?
  • Do we need new medicines?
  • Which type of new medicines we need?
  • What needs to be done to get new medicines out?
  • Is increase of spending on RD the only solution?
  • What about new medicines for public health needs?
  • What can regulators do?

15
New initiatives to streamline drug approval
process
16
Research spending
17
and product submissions to FDA
18
Increase in certain segments of development costs
19
Project Failure is Highest in Phase II
Mean Probability Of Success Of Completing Stage
PoS
CMR data based on cohort approach looking at
fate of NCEs entering phase 1996-1998, with
progression decision made by 2001
adapted from Ashton GA, Joshua PJ. Industry
success rates 2002. CMR International Ltd
20
Three dimensions of Critical Path
21
Poorly developed areas Paediatric medicines
  • Paediatric indications based on evidence only
    approximately 50 of use has backing by clinical
    research
  • Incentives for paediatric research created in
    several countries (exclusivity rights increased
    etc.)
  • US
  • EU
  • Not much specific regulatory guidance
  • Lack of paediatric formulations needed ARVs

22
Recent safety concerns and withdrawals COX2
inhibitors in focus
  • Are regulatory models used to assess safety
    appropriate?
  • Independence of pharmacovigilance from
    authorization staff
  • US Congress interested and investigates issues
  • Can safety be predicted in a better manner?
  • Are new regulatory guidance documents needed?

23
Pharmacogenetics (PGx) significant potential to
address some of the challenges
  • Pharmaceutical companies and regulators are
    actively exploring PGx applications. Draft
    guidance issued by some regulators, discussions
    in ICH environment
  • CIOMS report Impact of Pharmacogenetics on Drug
    Discovery and Development,
  • key development drivers and hurdles relevant to
    the
  • implementation of PGx in drug development
  • the potential role PGx may play in the drug
  • development process

24
New regulatory pathways to assure quality, safety
and efficacy of medicines for public health needs
in developing world
  • WHO Prequalification Program
  • US FDA tentative approval process for ARVs
  • EU Article 58 process

25
WHO Prequalification
  • The UN prequalification program is an action plan
    for expanding access to medicines for the hardest
    hit by
  • HIV/AIDS
  • Tuberculosis
  • Malaria
  • by ensuring quality, efficacy and safety of
    medicines procured using international funds

26
Why the prequalification is needed?
  • Problems
  • Millions of people living with HIV/AIDS,
    tuberculosis and malaria, have no or limited
    access to treatment
  • Substandard products widely available and in
    circulation
  • Weak/absent QA systems of medicines supply chain
  • Lot of money invested in procurement ?no
    harmonized quality assurance system available for
    procurement organizations/initiatives
  • Risks
  • Sourcing of poor quality products or even
    counterfeit medicines? risk to patients,
    treatment failure, resistance

27
Prequalification basic principles
  • Rigour regulatory approach to ensure quality,
    safety and efficacy
  • Voluntary for participating manufacturers
  • Legitimate - General procedure and standards
    approved through WHO Expert Committee system
    involving all WHO Member States and WHO Governing
    bodies
  • Widely discussed
  • FIP Congress, Nice 2002
  • Supported by ICDRA in 2002 and 2004, representing
    more than 100 national drug regulatory
    authorities
  • Transparent (all information available on the web
    site http//www.who.int/medicines/)
  • Open to both innovators and multisource/generic
    manufacturers
  • No cost for applicants (manufacturers) during
    pilot phase

28
Prequalification misunderstandings and critics
  • Too high standards increasing prices
  • Too high and unnecessary standards for
    developing countries
  • Too bureaucratic and slow, not proactive and
    not able to provide products
  • Too low standards
  • . " This leaves the impression with readers that
    the ARVs approved by WHO are in fact generic
    products that are interchangeable with their
    innovator cousins. From available documents,
    however, we conclude that they are copy products
    with unknown quality, safety and efficacy
    profiles".

29
How prequalification is organized
  • Role of WHO Managing and organizing the project
    on behalf of the United Nations.
  • provide technical and scientific support and
    guarantee that international norms and standards
    are applied all through the process including
    assessment, inspection (GMP, GCP, GLP) and
    quality control
  • Partners
  • UNICEF, UN Population Fund (UNFPA), UNAIDS and
    with the support of the World Bank
  • Anti-malarial and anti-TB products Roll Back
    Malaria and Stop TB (Global Drug Facility)
  • Actors Mainly assessors and inspectors of
    National DRAs as well as National Quality Control
    Laboratories of PIC/S and ICH member countries

30
Assessment procedure
  • I. Assessment of products dossiers i.e. quality
    specifications, pharmaceutical development,
    bioequivalence etc.
  • teams of professionals from national drug
    regulatory authorities (DRA) Brazil, Canada,
    Denmark, Estonia, Finland, France, Germany,
    Hungary, Indonesia, Malaysia, Philippines, Spain,
    South-Africa, Sweden, Switzerland, Tanzania, UK,
    Zimbabwe ...
  • II. Inspections
  • Manufacturing site (final product, packaging)
  • Active pharmaceutical ingredient (API)
  • Research laboratory or Contract Research
    Organization (CRO)
  • Teamwork of inspectors
  • WHO representative (qualified GMP inspector)
  • Inspector from well-established inspectorate
    (Pharmaceutical Inspection Convention Scheme
    countries) Australia, Canada, UK, France, Italy,
    Switzerland,
  • Quality control analysis - upon need but not
    always necessarily before prequalification and
    supply, increasingly as part of follow-up

31
Current status 2005
  • Started with HIV/AIDS products in 2001 malaria
    and TB products joined later
  • Prequalified products Submitted
  • 95 HIV related medicines - 289
  • 8 anti-tuberculosis medicines - 153
  • 2 anti-malarial medicines - 46
  • 105 488
  • Ongoing assessments and follow-up
  • Products
  • Manufacturing sites
  • CROs

32
Ongoing monitoring and requalification
  • Samples taken after supply
  • Routine inspections and additional inspections
  • Changes and variations controlled
  • Products and manufacturers
  • Requalification (re-assessment) every 3 years
  • World Health Assembly resolution WHA57.14 of May
    2004
  • Public reports
  • WHO Public Assessment Report (WHOPAR)
  • WHO Public Inspection Report (WHOPIR)

33
Prequalification
  • Good news
  • Relatively large number of products and suppliers
    indicated
  • Many potential suppliers appreciating feedback
    and willing to improve
  • Unique knowledge obtained about generic products
  • De-listed products coming back to the
    prequalified products list
  • Bad news
  • Only limited number of products have met the
    required standards
  • A number of de-listings from the prequalified
    products list in 2004
  • Takes time to get into compliance
  • Data to be generated, tests carried out
  • GMP upgrade needed
  • Bad quality generics may undermine the public
    confidence in generics
  • Quality assurance has its price!

34
Lessons to be learned
  • Quality can not be assessed, tested or inspected
    into the product, BUT
  • It has to be built into it!

35
http//mednet3.who.int/prequal/
36
(No Transcript)
37
US FDA tentative approvals
  • Exactly the same standards for assessment as for
    US internal market
  • The same inspection standards
  • The same post approval surveillance
  • When IP rights allow (patents and other
    exclusivity rights) can enter US market
  • Limited to ARVs as linked to specific program
    does not cover other product groups

38
Article 58 LEGAL BASIS AND SCOPE
  • Article 58 of Regulation (EC) No 726/20041 (the
    Regulation) establishes a mechanism whereby the
    European Medicines Agency (EMEA) may give a
    scientific opinion, in the context of cooperation
    with the World Health Organization (WHO), for the
    evaluation of certain medicinal products for
    human use intended exclusively for markets
    outside the Community.
  • The Committee for Medicinal Products for Human
    Use may, after consulting the World Health
    Organization, draw up a scientific opinion in
    accordance with Articles 6 to 9.

39
(No Transcript)
40
Article 58 Why?
  • Under new EU legislation the EU Commission will
    no longer license medicinal products unless they
    are to be placed on the market in the EU.
  • Applicants were not able to get marketing
    authorization in the EU for products that had no
    market
  • WHO CPPs not issued under such circumstances no
    basis for acceptance by other DRAs
  • Commission did not intend to kill incentives from
    companies to address public health issues outside
    the EU

41
How Article 58 will work?
  • Strong cooperation with the WHO
  • WHO gate keeper (determines if product is of high
    public health value)
  • WHO can send observers to CHMP
  • WHO can provide experts to EMEA
  • Procedure resembles centralized procedure same
    standards
  • Outcome not MA but "scientific opinion for WHO"
  • WHO type CPP will be issued
  • EPAR like document will be made public

42
Specific non-EU medical needs
  • Medicines for non-EU use only due to
  • - Specific epidemiological situation
  • - Specific socio-economical conditions
  • - Specific logistical conditions
  • Vaccine examples
  • - Pneumococcal vaccines with adapted
  • composition
  • - Multidoses containing thiomersal etc.

43
(No Transcript)
44
What type of medicines we have? 2. Generic
products
  • The term generic product has somewhat different
    meanings in different jurisdictions. Therefore,
    term multisource pharmaceutical product is
    preferred by WHO.
  • Where the term generic product is used, it means
    a pharmaceutical product, usually intended to be
    interchangeable with the innovator product, which
    is usually manufactured without a license from
    the innovator company and marketed after expiry
    of the patent or other (e.g. data) exclusivity
    rights.
  • Multisource pharmaceutical (generic) products are
    pharmaceutically equivalent products that may or
    may not be therapeutically equivalent.
    Multisource pharmaceutical products that are
    therapeutically equivalent are interchangeable

45
What standards are need for generic medicines?
  • For generic medicines the manufacturer has to
    prove that the product meets all quality
    requirements
  • In case of safety and efficacy it refers to the
    originator's research
  • To prove the therapeutic interchangeability it
    has, as a rule, to carry out bioequivalence
    studies (small scale clinical trials in healthy
    volunteers to examine if the test drug has
    essentially the same blood concentration pattern
    of active ingredient as the originator.
  • It is assumed that if the blood concentrations
    are essentially the same the safety and efficacy
    profile is also the same.

46
Standards for generic drugs first priority
  • WHO continues to issue Global standards for
    generic medicines and regulatory topics for
    public health importance

47
39th WHO Expert Committee on Specifications for
Pharmaceutical Preparations, 25-29 October 2004
(I)
  • Draft Guidelines
  • FDC -WHO-QAS04_108 (Fixed Dose Combination
    guidelines)
  • GMP_Herbal_RevJuly-04_QAS050
  • Interchangeability-WHO-QAS_093Rev3_23Sept04
    (bioequivalence)
  • QAS_055_Rev1_validation (supplementary to GMP)
  • QAS_066_Rev3_sampling (to replace 1990 guideline)
  • QAS_068_GDP see next slide for details
  • QAS047_Rev1_Water (GMP)
  • Guidelines on MP HVAC (Rev 4) (GMP Heating,
    ventilation and air conditioning for non-sterile
    dosage forms)
  • http//www.who.int/medicines/organization/qsm/expe
    rt_committee/expertcomm.shtml

48
(No Transcript)
49
What is WHO doing in order to reduce quality and
regulatory gaps?
  • Assessing regulatory capacity upon request
  • Supporting capacity building and training of
    regulators
  • Issuing norms and standards and guidance
    materials
  • Preparing training tools, organizing training
    seminars and workshops on variety of topics as
    requested by countries - GMP, MA of Generic
    Drugs, GCP, GLP, Pharmacovigilance etc.
  • Facilitating information exchange
  • Supporting regional harmonization initiatives
  • Favoring networking and cooperation
  • Providing technical assistance upon request

Ultimate goal improve access to quality drugs
for all citizens
50
International Conference of Drug Regulatory
Authorities
  • Biennial unique forum of regulators
  • Brings together more than 100 countries

51
Information exchange.WHO Drug Informationhttp//
www.who.int/druginformation/
52
Unfinished agendas 1. In many countries ABC
recommendations of this document to implement
effective drug regulation of medicines are still
not implemented
S
53
2.Unregulated online shopping threat for public
health
54
3. Counterfeit medicines Global threat to public
health
55
3. Counterfeit medicines no country is immune
Figure 1. The Number of Investigations of
possible counterfeit drugs by the FDA has been
rising (Figure Margaret Shear, Public Library of
Science, cited form Cockburn R, Newton PN,
Agyarko EK, Akunyili D, White NJ (2005) PLoS Med
2(4) e100.
56
As health professionals, in public and private
sector, as an international community ...we have
a lot left to do all of us, together, things
that do matter, in right time and in right order
www.who.int/medicines
Write a Comment
User Comments (0)
About PowerShow.com