Transcript EMP Technical Briefing Seminar ECBS: Vaccines and Biotherapeutic products Dr Ivana Knezevic TSN/EMP/HIS WHO, Geneva, 31st October 2013

EMP Technical Briefing Seminar
ECBS: Vaccines and
Biotherapeutic products
Dr Ivana Knezevic TSN/EMP/HIS
WHO, Geneva, 31st October 2013
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
2|
Ivana Knezevic |
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.
3|
Ivana Knezevic |
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.
4|
Ivana Knezevic |
–
–
WHO norms and standards for biologicals
Global written standards
Global measurement
standards
Scientific evidence
1) Standardization of assays
2) Further development
and refinement of QC tests
3) Scientific basis for setting
specifications
Reference preparations for
vaccines and biotherapeutics
Measurement
standards:
essential elements for development, licensing
and lot release
5|
Ivana Knezevic |
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
Ivana Knezevic
Timeline for WHO Written Standards
2013
rDNA
Typhoid
NC of adjuvanted
IPV
Post-app. Changes
RRA for AAs
GMP
HPV
RRA of BTP
CTC
Informal consultation
ECBS submission
Implementation workshop
2014
2015
Timeline for Written Standards
Projects 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)
Ivana Knezevic
Development of measurement standards
for biotherapeutics, 2008 - 2013
1. Insulin-like growth factor (2nd IS)
1. Chorionic gonadotrophin (5th IS)
2. Parathyroid hormone, 1-84 (1st IS)
2008
2009
2010
1.
2.
3.
4.
Thyroid stimulating antibody (2nd IS)
Follicle stimulating hormone (2nd IS)
Sex hormone binding globulin (2nd IS)
G-CSF (2nd IS)
2011
1. Dihydrostreptomycin (3rd IS)
2. TGF beta-3 (1st IS)
1.
2.
3.
4.
5.
9|
2012
1. TNF alpha (3rd IS)
2. Peg G-CSF (1st IS)
Urinary follicle stimulating hormone and urinary luteinizing hormone (5th IS)
Erythropoetin, recombinant for bioassay (3rd IS)
High molecular weight urokinase (2nd IS)
IL 29 (1st RR)
IL 2 (2nd IS)
Ivana Knezevic |
2013
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
Ivana Knezevic
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
Ivana Knezevic
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
Ivana Knezevic
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
Ivana Knezevic
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 intercountry 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
Ivana Knezevic
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
Ivana Knezevic
Key strategic drivers
Global public health
 Universal health
coverage
 Regulatory
convergence
 Regulatory science
21 |
Ivana Knezevic |
WHO context
 WHO reform
 EMP reorganization
 ICDRA 2014
Further information and contact
Biological standardization website:
www.who.int/biologicals
Immunization website: www.who.int/immunization
Contact details:
Dr David Wood (email: [email protected])
Dr Ivana Knezevic (email: [email protected])
Ivana Knezevic