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

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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)