who norms and standards · his/emp | who norms and standards –promoting quality and innovation...
TRANSCRIPT
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHO NORMS AND STANDARDS – PROMOTING Quality & innovation for health products
Technologies Standards and Norms Team
Essential Medicines and Health Products Department
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHO’S NORMATIVE WORK ON DIAGNOSTICS, MEDICINES AND VACCINES
Dr David Wood
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
IT'S THE CORE OF WHO'S CORE BUSINESS
The Constitution requires WHO “to develop, establish and promote international standards with respect to biological and pharmaceutical
products”.
This has been done for more than 60 years now
The norms and standards are established by Expert Committees
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHAT IS A WHO EXPERT COMMITTEE?
o Official Advisory Body to Director-General of WHO
o Established by World Health Assembly or Executive Board
– WHO Expert Committee on Specifications for Pharmaceutical PreparationsSecretary: Dr Sabine Kopp
– WHO Expert Group on International Non-proprietary Names
Secretary: Dr Raffaella Balocco
– WHO Expert Committee on Biological Standardization
Secretary: Dr David Wood
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
LINK WITH WHO GOVERNING BODIESWHO Expert Committee reports are presented to the Executive Board
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHO GLOBAL STANDARDS AND NORMS – ROBUST, DURABLE and RESPONSIVE TO PUBLIC
HEALTH NEEDS
Global written standards Global measurement standardsTools for product development,
licensing and lot release
INNsA single name for a
substance for use globally
Tools for appropriate regulation
of quality, safety and efficacy
sofosbuvirnow in Essential
Medicines List to
treat
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
REFERENCE REAGENTSWHO MEASUREMENT STANDARDS
Dr Micha Nübling
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
ZIKA VIRUS
WHO | “Public Health Emergency of International Concern” (01.02.16)
o Call for Zika virus research and development
o , Vaccines, TherapeuticsDiagnostics
Zika virus outbreak
o in parts of the Americas
o since end 2014
o 0.5 - 1.5 mio infected
o potential association withmicrocephaly in newborns
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
Diagnostics development and evaluation need reference materials
o design of Zika in vitro diagnostics (IVDs)
o calibration, validation
o comparison of different IVDs
WHO Teleconference (01.02.16)
o coordinate global harmonisation efforts for Zika IVDs
o availability of materials
o assignment of tasks to WHO Collaborating Centers
ZIKA VIRUS
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHO COLLABORATING CENTERSblood products, in vitro diagnostics
NIBSC, UKNIBSC, UK
FDA CBER, USFDA CBER, US
PEI, DEPEI, DE
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
ZIKA VIRUSInternational Reference Reagents in preparation
NIBSC
Antibody and antigen assays
o convalescent sera
o virus-like particles
PEI
Nucleic Acid Amplification Technology (NAT) assays
o cell culture virus (inactivated), in plasma/urine
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHO GLOBAL MEASUREMENT STANDARDS for blood products and IVDs
Lifecycle of a standardization project
o Evaluation of the need for a global standard
• input from stakeholders
o Endorsement of the project by ECBS
o Performance of the project
• by a WHO Collaborating Center
o Establishment of global standard by ECBS, unitage
o Provision of measurement standards by WHO CC
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHO GLOBAL MEASUREMENT STANDARDS for blood products and IVDs
Example
Measurement Standards for Ebola diagnostics
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
0
100
200
300
400
500
600
700
800
900
1000No interpretation Indeterminate Negative Confirmed
EBOLA VIRUS IVDs
Intended Use
o Diagnosis of infection
o Surveillance
Ebola IVDs
o NAT assays
o antigen assays
o antibody tests
WHO weekly reports: Sample Count (Guinea)
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHO MEASUREMENT STANDARDSfor blood products and IVDs
Ebola NAT standard
o Recombinant virus particles
• parts of the Ebola RNA packaged in HIV-1 structural proteins
• 2 different preparations: cover whole Ebola genome
• introduction of stop codons
• non-infectious
o Collaborative study
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
HARMONISATION OF EBOLA NATSby WHO International Reference Reagent
BEFORE AFTER
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
HARMONISATION OF ANTIEDV ASSAYS
Ebola Antibody standard
o Convalescent plasma from survivor
o Collaborative Study reactive in assays of different design
ELISAs
• Glycoprotein
• Nucleoprotein
• whole virus
Neutralisation assays
• Wt virus (BSL4)
• Pseudotype
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHO MEASUREMENT STANDARDSfor blood products and IVDs
ECBS 2015
o Ebola NAT and Antibody standards established as measurement standards
o In total 12 measurement standards established
o 16 new projects on measurement standards endorsed
WHO Measurement Standards
o worldwide recognized tools in biological standardization
o among WHO priority tasks in PHEICs (Zika, Ebola)
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
THE LAST MILE FOR VACCINE DELIVERY – A NEW
STANDARD TO VALIDATE STABILITY
Dr Ivana Knezevic
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHAT IS THE PROBLEM ?
o Almost all vaccines used in immunization programs today are
licensed for storage and distribution within a supply chain of
2°C to 8°C
Problem reported by IVB/ EPI:
� Extremely difficult in countries with limited cold chain and ice pack
� Increasing cost and/or logistical constraints of vaccine delivery
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHERE VACCINE STABILITY MIGHT BE AFFECTED?
VACCINE
STORAGE AT MANUFACTURER’S SITE
EXCURSIONS
RECONSTITUTION
STORAGE AT CLINIC
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHY DO WE NEED A NEW STANDARD?
o Many vaccines are stable beyond 2 – 8°C for some time but they cannot be used as such without a proper licensing
o Label changes to support decision making for use of a vaccine following exposure:
• to specific temperature
• for a short period of time
� New standard is needed to guide regulators and manufacturers to assure vaccine stability throughout the life cycle of the product including the last mile towards each child or adult
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHEN AND HOW IS A NEW STANDARD DEVELOPED?
o 2010 – 2015: novel approaches for assessing stability of vaccines intended
for use in extended controlled temperature chain (ECTC) led to many
technical questions
o Consultation process with regulators, industry and other experts:
• different opinions and views - great enthusiasm or resistance
• from initial misunderstandings, consensus developed with stakeholders
on definitions, guiding principles, and technical requirements
• http://www.who.int/biologicals/areas/vaccines/controlledtemperaturechain/en/
o WHO Collaborating Centers and many experts from various areas of
vaccine development, regulation and immunization
o Collaboration between IVB/EPI and EMP/TSN/NSB
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
NEW GUIDANCE FOR REGULATORS AND INDUSTRY BUT ALSO FOR IMMUNIZATION STAFF
o Guidelines on stability evaluation of
vaccines for use under extended
controlled temperature conditions
(ECTC) – adopted by the ECBS in
2015
o Vaccine management and logistics
o Film in 3 episodes on Youtube
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
THE LAST MILE FOR VACCINE DELIVERY – EXAMPLES
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
THE LAST MILE FOR VACCINE DELIVERY – EXAMPLE 2
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHAT ARE THE ADVANTAGES OF EXTENDED CONTROLLED TEMPERATURE CONDITIONS?
o ECTC typically involves a single excursion of the vaccine into
ambient temperatures not exceeding +40°C and for duration of
a specific number of days, just prior to administration
o Lower cost
o Better immunization coverage
o Reaching those who cannot be reached due to the limitations of
the cold chain in remote areas
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
FROM STANDARDS TO VACCINES
Mikael, age 11, in Banikoara
Mikael was the first person
ever vaccinated with
MenAfriVac in a CTC.
When he grows up, he wants
to be a doctor.
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
POOR QUALITY MEDICINES FOR PATIENTS – NO WAY!!
Dr Sabine Kopp
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
QUALITY ASSURANCE A KEY ELEMENT
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
SOME REALLY "GOOD" EXAMPLES
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
PATIENTS MAY HAVE CHALLENGES IN MAKING JUDGEMENTS ABOUT MEDICINES' QUALITY
APPEARANCE SMELL TASTE
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
TOOLS FOR DEVELOPMENT, MANUFACTURE, DISTRIBUTION, REGULATORY REQUIREMENTS,
QUALITY CONTROL
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
EXAMPLE OF CONTAMINATED ACTIVE INGREDIENT
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
IN THE NEWS: DATA INTEGRITY
FDA Warns … Drugmaker Over Major Data Integrity Violations at Three Plants (Posted 09 February 2016)
“The US Food and Drug Administration (FDA) on Tuesday released a warning letter …
after inspections at three … manufacturing facilities revealed data integrity violations …
deleting, overwriting, changing integration parameters, and altering computer date and
time settings were done for raw materials, in-process testing and finished active
pharmaceutical ingredients…”
WHO's response: Good data and
record management practices
o New tool for inspectors, first international
guidance
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
SAFE QUALITY MEDICINES
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
THE INVISIBLE WORLD OF INN - HOW A LITTLE KNOWN WHO PROGRAMME HAS CHANGED THE WORLD OF
MEDICINES
Dr Raffaella Balocco
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHAT'S IN A NAME?
Letters?
Images?
Safety
Quality
Information
RegulationRational use
Procurement
Efficacy
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
Ebola
Hepatitis C
Monoclonal Antibodies
galidesivir
sofosbuvir
(now in EML)
trastuzumab emtansine
FDA ado-trastuzumab
INNs
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
INNs
o Unique name
o Distinctive in sound and spelling
o Not liable to confusion with other names in common use
o Formally placed by WHO in the public domain
o Can be used without any restriction to identify pharmaceutical
substances
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
INN A GLOBAL NAME?
epoetin alfa (2x)
epoetin zetaepoetin kappa
(generic recombination)
epoetin alfa biosimilar 1
epoetin lambda
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
BIOLOGICALS ARE MORE COMPLEX
o The complexity of substances
o The number-induced difficulty
o The emerging of new types of substances (new policies?)
Interferon betaInterferon betaInterferon betaInterferon beta AspirinAspirinAspirinAspirin
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
HISTORY OF THE BIOLOGICAL QUALIFIER (BQ)
Some NRA’s requested a global means to trace and track back
biologicals
The BQ Proposal developed in consultation with experts and
NRAs and published in Jul 2014
Extensive feedback-meetings-web consultative process etc from
all sectors guiding modification of the Proposal
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
RESPONSE FROM WHOM?
Academic Government Manufact'rs Industry
Clinical org Comms org Funding org Patient org
Pharm'st org Personal
1 - strongly disagree
2 - disagree
3 - partially agree
4 - agree
5 - strongly agree
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
SUMMARY OF CURRENT PROPOSAL
BQ for ALL biological medicines to identify drug substances made by 1 process under 1 quality system
BQ assigned to a BQ Applicant who permits MAHs to use it for products containing the drug substance
Used to minimise mis-prescription and/or dispensing, pharmacovigilance & global transfer of prescriptions etc.
BQ is assigned by an automated online system
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
CONCLUSION
Majority of stakeholders support BQ, but there is some opposition.
BQ Proposal modified in response to objections & suggestions receiving further positive and negative feedback.
Final BQ Proposal recommended by the INN Expert Group
(October 2015)
INN will carry out impact assessment study and, if/when appropriate implement BQ
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
INN IS SIMPLE
“Simplicity is the ultimate sophistication”
Leonardo Da Vinci
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
A historical conclusion
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
The first international biological reference
preparation, 1925
Hazel Davies (Australia), diagnosed with
type I diabetes in 1921, photographed 2
years before she celebrated her 100th
birthday
HIS/EMP | WHO norms and standards – promoting quality and
innovation for health products
WHO's normative work on
biologicals, diagnostics, medicines
and vaccines has been part
of our core business
since the very start….
WHO Technical
Report Series
Number 1
We intend to continue the
good work
of our predecessors….
WHO Technical
Report Series
Numbers 1000, 100x, 10xx?