“The approaches to the regulation of biological medicinal products in the Republic of Kazakhstan” Illustrates the current norms in place in Kazakhstan for the marketing authorization of pharmaceutical products and the dossier requirements for biotherapeutics & biosimilars

1. The approaches to the regulation of biological
medicinal products in the Republic of Kazakhstan
The National Center for Drug Expertise, Medical items and Equipment
Ministry of Public Health
Republic of Kazakhstan
Sh. Baidullayeva
Head of Department for Pharmacological Assessment
15-16 мая 2013, Москва
Биотерапевтические препараты. Современные вызовы и регуляторные практики. Подходы к
гармонизации.

2. 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
MinistryofPublicHealth
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

3. NCDE’s main units
Medicinal 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

4. http://www.dari.kz

5. 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)

6. Registration dossier assessment
Registration 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

7. Biosimilars
Up 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

8. 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)

9. 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

10. 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

11. 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:
Vaccines
Insulin
Monoclonal antibody
Erythropoietin
 Low-molecular-weight heparins
Interferon
Granulocyte-colony stimulating factor
Somatropin

12. 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

13. 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

14. 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

15. 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

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

17. 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

18. 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

19. Thank you for attention!
Thank you for attention!
Charyn Canyon