4. prof. shinar baidullaeva - national center for medicines, medical devices and medical equipment...

The approaches to the regulation of biological medicinal products in the Republic of Kazakhstan

The National Center for Drug Expertise, Medical items and EquipmentMinistry of Public HealthRepublic of Kazakhstan

Sh. BaidullayevaHead of Department for Pharmacological Assessment

15-16 мая 2013, МоскваБиотерапевтические препараты. Современные вызовы и регуляторные практики. Подходы к

гармонизации.

Pharmaceutical marketing authorization pathway in Kazakhstan

MPhACC’s** as a regulatory body Kazakhstan Ministry of Public health

MPhACC’s** as a regulatory body Kazakhstan Ministry of Public health

The National Center for Drug Expertise, Medical items and Equipment’s on expert body in medicinal products regulation

Registration dossier

Ministry of Public H

ealth

Registration dossier

assessment

Marketing authorization’s based on positive

conclusions of the NCDE*

*NCDE - The National center for drug expertise, medical items and equipment

**MPhACC - the Medical and Pharmaceutical activity control Committee

NCDE’s main unitsMedicinal product Medical devices

Primary expertise department Primary expertise department

Department for Pharmaceutical Assessment

Department for Medical devices Assessment

Department for Pharmacological Assessment

Labs

Physical Chemistry Lab

Microbiologically Lab

Republican immunobiological lab

Pharmacological Lab/BA&BE Lab

Animal house

Group on non-clinical&clinical studies

Department for quality&safety assessment (certification)

11 regional branches

http://www.dari.kz

Pharmaceutical marketing authorization rules have been defined by:

the Kazakhstan Health Code (18.09.2009)

the MoH Orders under №735 (18.11.2009) and 736 (18.11.2009)

Registration dossier assessmentRegistration dossier assessment by NCDE consists of 4 consecutive

stages:1) primary expertise – the main aim’s to check the registration dossier completeness for meeting current requirements, adequacy of the finished product and reference standards samples for a three-time analysis

2) analytical tests at the test lab –the aim’s to perform tests for checking the quality of FPS to be in conformity with an Analytical normative document developed in accordance with Finished product specification and Kazakhstan Pharmacopeia, EPh, USP, BP

3) pharmaceutical assessment – it’s an expertise of pharmaceutical part of the dossier, namely development pharmaceutical form, manufacturing, impurities assessment, data stability, etc.

4) pharmacological assessment – it’s an expertise conducted for pharmacological part of the dossier, namely non-clinical studies&clinical trials data, pharmacovigilance , Risk management plan

BiosimilarsUp to September, 2009, there hadn’t been any requirement for marketing authorization of biosimilars in Kazakhstan

In the Kazakhstan Health Code the first definition of “biosimilars” was accepted only in September, 2009

Definitions “Biological medicinal product” and “Biosimilars”

Biological medicinal products are the products containing biological proteins (hormones, cytokines, blood clotting factors, including low molecular weight heparin, insulin, monoclonal antibodies, enzymes, colony stimulating factors, products that have been developed on the basis of tissue cells obtained by genetic engineering and hybridoma technology)

Biosimilars is a reproduced biological medicinal product that is claimed to be similar in quality, safety and efficacy to innovative reference biological medicinal product with a similar international non-proprietary name that has been registered before

The Kazakhstan Health Code of Republic (18.09.2009)

Dossier Requirements

For marketing authorization of the original medicinal product, including immunotherapeutic and radiopharmaceutical products, an applicant for registration provides the whole list for the required registration dossier

MoH Order under №735 dated 18/11/2009,paragraph 15

Dossier Requirements for biosimilar It is necessary to provide the following data for biosimilar marketing authorization:

- active substance and finished product of biosimilar quality data compared with the original biological product

-reports on comparative preclinical studies of biosimilar and original biological product

-reports on biosimilar safety, efficacy and immunogenicity through comparative clinical trials versus original biological product

- Pharmacovigilance Master File marketing authorization holder and Risk management plan for the proposed product

MoH Order under №735 dated 18/11/2009,paragraph 23

Kazakhstan record book makes 7131 medicinal products by 10th May 2013, with it all 296 is biological medicinal products

Registered under the following biological product groups:VaccinesInsulinMonoclonal antibodyErythropoietin Low-molecular-weight heparinsInterferonGranulocyte-colony stimulating factorSomatropin

The following product brackets have been applied for registration as biosimilrs from 2010 to 2012

Active substance name Number application Decision

Peg interferon (India) 1 Refused

Erythropoietin (Korea) 1 Refused

Low-molecular-weight heparin (India)

2 Refused

Somatropin (Russia) 1 Refused

Interferon beta (Ukraine) 1 Refused

Refusal for registration

- No proof for quality, purity and potency similarity with the reference biological product

- The lack of comparative non-clinical studies&clinical trials

- Multi-reference for different stages of product development (quality tests, preclinical and clinical studies)

- The lack of Risk management plan

The following product brackets have been applied for registration as biosimilrs in 2013

Active substance name Number application

Decision

Low-molecular-weight heparin (India) 1 Under review

The monoclonal antibody - Infliximab (Korea)

1 Under review

The monoclonal antibody Rituximab (India)

1 Under review

Reference Biological medicinal product

The original biological product is the reference product

In case of non-availability of the original biological product in Kazakhstan, there is an option to regard the authorized products in the ICH-countries

National Center for Drug Expertise makes use of European Medicines Agency guidelines over biosimilar registration dossier

assessment

The reproduced Insulin products Marketing authorization was granted before September, 2009, for some insulin products (India, Ukraine, Poland)

However they are not considered as biosimilars and are not use in clinical practice

Amendments to authorization requirements

Reproduced biological medicinal products registered earlier than 2009, upon maturity deadline will be submitted for registration, however not for re-registration , in accordance with biosimilars requirements

Draft Amendment to MoH Order №735

Thank you for attention!

Thank you for attention!

Charyn Canyon