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ECBS: Vaccines and Biotherapeutic products
Dr Ivana Knezevic TSN/EMP/HIS
WHO, Geneva, 31st October 2013
EMP Technical Briefing Seminar
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Outline
WHO International Standards - written (eg, Guidelines, Recommendations)- measurement (Int. Standards and Reference Preparations)
ECBS 2013 – main outcomes Biotherapeutic Products (BTP) Similar Biotherapeutic Products (Biosimilars) Collaborating Centers Strategic issues
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World Health Organization (WHO) WHO is a specialised agency of the UN serving as the directing
and coordinating authority for international health matters and public health on behalf of its 194 Member States.
Principle objective - the attainment by all people of the highest possible level of health.
WHO is responsible for providing leadership on global health matters, shaping the health research agenda, setting norms and standards, articulating evidence-based policy options, providing technical support to countries and monitoring and assessing health trends.
Setting norms and standards and promoting their implementation is affirmed as a core function of WHO for the period 2008-2013.
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WHO Biological Standardization WHO has played a key role for over 60 years in establishing the WHO
Biological Reference Materials necessary to standardize biological materials as well as developing WHO guidelines and recommendations to assure the quality, safety, and efficacy of biological products.
These norms and standards, based on scientific consensus achieved through international consultations, assist WHO Member States in ensuring the quality and safety of biological medicines and related in vitro biological diagnostic tests worldwide.
The Organization accomplishes this biological standardization work through– its biological programme coordinated by a Secretariat at WHO HQ;– the WHO Expert Committee on Biological Standardization (ECBS)
selected from an Expert Advisory Panel on Biological Standardization; and
– WHO Collaborating Centres for Biological Standardization.
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WHO norms and standards for biologicals
Global written standards
Global measurement standards
Scientific evidence
Measurementstandards: essential elements for development, licensing and lot release
1) Standardization of assays2) Further development and refinement of QC tests3) Scientific basis for settingspecifications
Reference preparations for vaccines and biotherapeuticswww.who.int/
biologicals
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Guidelines/ recommendations under development/ revision
ECBS 2013 – main outcomes– Biotherapeutic Products made by rDNA technology - ADOPTED– Typhoid conjugate - ADOPTED– Nonclinical evaluation of adjuvanted vaccines - ADOPTED
Plan for ECBS 2014– IPV– Regulatory evaluation of post-approval changes – Regulatory Risk Assessment in the case of Adventitious Agents in already
licensed vaccines – "Scientific Considerations" rather than Guidelines Plan for ECBS 2015
– GMP for biologicals– HPV– Regulatory Risk Assessment of Biotherapeutic Products– Regulatory expectations for Controlled Temperature Chain
2013 2014 2015
rDNATyphoidNC of adjuvantedIPVPost-app. ChangesRRA for AAsGMPHPVRRA of BTPCTC
Informal consultation
ECBS submission
Implementation workshop
Timeline for WHO Written Standards
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Timeline for Written StandardsProjects with unclear timeline
• Meningitis B• Flu vaccines for regulators in non-producing
countries• Vector based vaccines• Update of guidelines on clinical evaluation of
vaccines• Product Specific Guidelines on Similar
Biotherapeutic Products (SBP)
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20132008 2009 2010 2011
Development of measurement standards for biotherapeutics, 2008
- 2013
2012
1 .Urinary follicle stimulating hormone and urinary luteinizing hormone (5th IS)
2 .Erythropoetin, recombinant for bioassay (3rd IS)3 .High molecular weight urokinase (2nd IS)
4 .IL 29 (1st RR)5 .IL 2 (2nd IS)
1 .Thyroid stimulating antibody (2nd IS)2 .Follicle stimulating hormone (2nd IS)
3 .Sex hormone binding globulin (2nd IS)4 .G-CSF (2nd IS)1 .Chorionic gonadotrophin (5th IS)
2 .Parathyroid hormone, 1-84 (1st IS)
1 .Insulin-like growth factor (2nd IS)
1 .Dihydrostreptomycin (3rd IS)
2 .TGF beta-3 (1st IS)
1. TNF alpha (3rd IS)
2. Peg G-CSF (1st IS)
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Biotherapeutic Products (BTP) including Similar Biotherapeutic
Products (SBP) WHO survey on regulation of BTP and SBP: to understand situation in various
regions/countries:– Diversity of national regulatory requirements in the region– Obstacles in developing and regulating BTP – Required clinical data for already licensed products– Definitions used for "originator" product and "copy product" in the case of SBP
Following networks have been involved:– PANDRH, AVAREF– APEC, ASEAN– Russian speaking countries
A possibility for survey for Industry Common objectives of all networks: 1) expertise and capacity building 2)
regulatory convergence and 3) efficient sharing of information and knowledge Expertise/ experience for evaluation of BTP is essential - need for technical
assistance
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Similar Biotherapeutic Products (SBP) 3rd implementation workshop on SBP: 14-16 May 2014 in Korea:
– Focus on clinical evaluation of SBP– Special considerations for evaluation of mabs– Case studies on selected topics
Regulators from APEC and ASEAN expressed interest for joint workshop on BTP and SBP
Follow up actions with PAHO in addressing the need for assistance to PANDRH
Regulatory risk assessment of products licensed without clinical data: case studies from countries (eg, Thailand, Brazil) and maybe Guidelines
Main theme of pre-ICDRA meeting in 2014: Biosimilars
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Implementation of standards - concept Following adoption of WHO Guidelines or Recommendations, a need for facilitating
implementation of guiding principles into regulatory and manufacturing practice is addressed: – Usually, the issues that are complex and/ or difficult for regulators to implement, are
identified during the consultation process – Drafting Group is presenting a proposal for facilitating implementation to the ECBS or
the Committee identifies a need for helping regulators General Topics
– Stability Evaluation of Vaccines, Vaccine Lot Release, Evaluation of Cell Substrates– Evaluation of Biotherapeutic Products, including SBP
Specific issues related to Vaccines or Biotherapeutic Products– Selected vaccines with complex issues such as:
• potency testing of rota vaccine, HPV• evaluation of combined vaccines based on DTP, typhoid conjugate, IPV• BTP: mabs, EPO, • SBP: Reference Product, comparability studies, quality parameters, extrapolation
of indication
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Implementation of standards - tools Implementation workshops:
– Lectures on selected topics– Case studies– Work in groups of 6-8 participants where regulators and manufacturers
discuss application of guiding principles to specific examples – Facilitators help clarifying the points needed for discussion and each
group comes up with a conclusion and key arguments that support their opinion
– In some cases, there is no consensus but options for proceeding further– Good learning opportunity but limited to certain number of workshop
participants (eg. 30-40 participants) Publications – meeting reports, case studies from implementation
workshops– Special issue in Biologicals – Vaccine Stability and Similar
Biotherapeutic Products E-learning tools, Webinars
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Collaborating Centers
Recent designations:– NIFDC – Jan 2013– PEI – Aug 2013
Recent re-designation:– NIBSC – July 2013
Current status: 8 CCs for standardization and evaluation of vaccines Additional expertise and broader experience available in CCs which has
increased capacity for responding to expectations of the users of standards
Concept of global CC with technical support to various regional and inter-country networks of regulators
Information on WHO web site for biologicals – revision of the page for CCs to provide regular update on the activities of CCs
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Strategic issues– Regulatory Science as a basis for Regulation of Biologicals– Role of WHO standards in facilitating regulatory convergence
• Provision of the most needed standards on time• Right balance between general principles and examples – unique role of
WHO• Science based regulation, consensus on critical aspects
– Making standards available is important but not enough. In addition:
• Regular communication with the users of WHO standards• Input from regulators, manufacturers and academia in developing and
implementing WHO standards• Involvement of WHO Collaborating Centers• Collaboration with other standard setting bodies
- Evolving concept• Great expectations in terms of broadening the scope to include cell therapy,
gene therapy but limited resources
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Key strategic drivers
WHO contextWHO reformEMP reorganizationICDRA 2014
Global public health Universal health
coverageRegulatory
convergenceRegulatory science
Ivana Knezevic
Further information and contact
Biological standardization website:
www.who.int/biologicals
Immunization website: www.who.int/immunization
Contact details:
Dr David Wood (email: woodd@who.int)
Dr Ivana Knezevic (email: knezevici@who.int)