“The regulatory landscape for biotech products in Ukraine” Illustrates the current norms in place in Ukraine for the marketing authorization of pharmaceutical products and the dossier requirements for biotherapeutics & biosimilars

1. Ukrainian State Expert Center
Ministry of Health of Ukraine
The regulatory landscape for
biotech products in Ukraine
Yuriy Gamazin,
Moscow, May, 2013

2. OBJECTIVE:
 The Objective of the National Programme of Ukrainian legistation
harmonization with the European Union approved by Law of Ukraine
No.1629-IV of March 18, 2004 is to achieve compliance of the legal
system of Ukraine with acquis communautaire taking into account the
criteria set by the EU for the countries intended to join the EU.
 Thus, the objective of the MOH is to harmonise Ukrainian regulations
on quality, safety and efficacy of medicinal products with the
Directives of the European Parliament and the European Council
relating to registration and circulation of medicinal products.

3. Medicinal products are allowed for use in Ukraine after their
state registration, except as provided by this Law
Law of Ukraine «On Medicines», 1996
(Section ІІ, Article 9)
Medicinal product can not be placed on the market of a
Member State unless a marketing authorization has been
issued by the competent authorities of that Member State in
accordance with this Directive or an authorization has been
granted in accordance with Regulation (EEC) No 2309/93.
Directive 2001/83 of the European Parliament and the
EU Council of November 06, 2001
(Title ІІІ, Chapter 1, Article 6)
Prerequisites for the use of medicinal productsPrerequisites for the use of medicinal products

4. Essential regulations for medicinal product
circulation
 Law of Ukraine “On Medicines”;
 Resolution of the Cabinet of Ministers of Ukraine No 376 “On Approval of
the Procedure for State Registration (Re-registration) of Medicinal
Products and Fee for Their State Registration (Re-Registration)” of May
26, 2005 (as amended by Resolution of the CMU No 717 of June 27,
2012);
 Resolution of the Cabinet of Ministers of Ukraine No. 73 “On Approval of
the Regulation on the Control of Conformity of immunobiological
Products Used in Medical Practice with the Requirements of National
and International Standards” of January 15, 1996;
 Resolution of the CMU No 902 “On Approval of the Procedure for State
Quality Control of Medicinal Products Imported to Ukraine” of
September 14, 2005

5. Essential regulations for medicinal product
circulation
 Order of the MOH of Ukraine No 426 “On Approval of the Procedure
for Conducting Expert Evaluation of Materials Pertinent to Medicinal
Products which are Submitted for State Registration (Re-
Registration) and Expert Evaluation of Materials about Introduction of
Changes to the Registration Documents during the Validity Period of
Registration Certificate" of August 26, 2005, (as amended by Order of
the MOH of Ukraine No 3 of January 04, 2013;
 Procedure for State Quality Control of Medicinal Immunobiological
Rroducts that are Used, Manufactured or Proposed for Use in Medical
Practice in Ukraine approved by Order of the MOH No 486 of
December 06, 2001

6. REGISTRATION
OF MEDICINAL PRODUCTS

7. Resolution of the CMU No. 717 of June 27, 2012
 State registration of medicinal products and medicinal immunobiological products
under unified procedure with taking into account particularities (Ministry of the
Health of Ukraine shall conduct state registration and re-registration of medicinal
products under procedure set forth for medicinal products).
 The state registration of a medicinal immunobiological product is certified by a
registration certificate of the medicinal product (medicinal immunobiological
product), not by a certificate of the state registration of the medicinal
immunobiological product;
 The MOH can decide to completely or temporarily prohibit the use of a medicinal
product by terminating the registration certificate if the medicinal product was not
released into circulation in the territory of Ukraine within two years from the date
of the state registration (re-registration) unless it is due to particularities of
manufacture and/or use of such medicinal product.

8. Order of the MOH No. 3 of January 04, 2013
Objective: Conformity with the acts of higher legal force (Law of
Ukraine “On Medicines”, Resolution of the CMU No 376 of May 26,
2005); improvement of the registration procedure in general.
 Revision of definitions;
 The proposed Order of the MOH is the single document for medicines
and medical immunobiological products;
 Strengthening the role of the MOH as the regulatory authority that
conducts the state registration of medicinal products and designates
the registration procedure in accordance with the recoomendations of
the expert body (The State Expert Center);

9. Order of the MOH No 3 of January 04, 2013
 Revision of the Section relating to amending registration materials,
classification of the types of changes;
 Submission, in the course of expert evaluation of the medicinal
product registration materials, a copy of a document confirming the
compliance of manufacture with the requirements of Good
Manufacturing Practice (GMP) that are in force in Ukraine, issued by
the State Administration of Ukraine on Medicinal Products (for
domestic manufacturers, a copy of the valid drug manufacturing
license shall be provided);
 Bringing the requirements for medicinal product labeling in line with
Article 12 of the Law of Ukraine “On Medicines”;
 Regulation of terms of the registration procedure

10. Order of the MOH No. 3 of January 04, 2013
 Requirements as to orphan drugs and specifics of their registration
materials;
 Definition of criteria and procedure for conducting additional studies
of medicinal products relating to:
pharmaceutical development,
confirmation of medicinal product quality,
preclinical studies,
medicinal product efficacy and/or safety studies,
studies of bioequivalence and equivalence of generic medicinal
products

11. Order of the MOH No 3 of January 04, 2013
 Requirements as to equivalence (interchangeability) studies of generics,
in particular:
 when in vivo equivalence study is not required;
 when equivalence study is required;
 conditions for biowaiver procedure;
 general aspects of test for dissolution;
 requirements for bioequivalence studies for different pharmaceutical
forms;
 requirements for confirmation of bioequivalence of additional doses of
the medicinal product;
 report on bioequivalence studies

12. Order of the MOH No 3 of January 04, 2013
 Special requirements are provided for registration of original
medicinal products and medicinal products that underwent the WHO
pre-qualification procedure and are included in the WHO list of pre-
qualified medicinal products used in treatment of socially dangerous
diseases (tuberculosis, HIV / AIDS, viral hepatitis, and rare diseases):
 Modules 1 and 2 (and their translation into Ukrainian of Russian) in hard copy.
Modules 3, 4, and 5 may be submitted by the applicant in soft copy;
 Expert evaluation of registration materials takes precedence and is conducted
free of charge;
 Pre-registration quality control of such medicinal products may be performed
under «Lot Release» procedure;
 Expert evaluation of the registration materials shall take not more than 90
working days from the date of receipt of the registration dossier by the Center

13. Order of the MOH No 3 of January 04, 2013
Control under «Lot Release» procedure is performed in the following
cases:
 the medicinal product is of high cost (equivalent to 500 EUR or more)
and is imported to Ukraine in limited amounts;
 Sterility, Microbiological purity, or other parameters are evaluated
under this procedure if their testing requires large number of specimens
and the cost of one specimen is equivalent to 100 EUR or more;
 if none of the authorized laboratories has at disposal the equipment
required for performing control tests for certain quality parameters;
 the medicinal product is of limited use (orphan drug).

14. Biosimilars in Ukrainian legislation
Medicinal immunobiological products include allergens, antigens, vaccines
(anatoxins), cytokines, immunomodulators of bacterial origin, as well as
those that are based on organ and tissue preparations, products
obtained from human blood and plasma, immune sera, immunoglobulins
(including monoclonal antibodies) , probiotics, interferons, other medical
products intended for use in medical practice for treatment, specific
prevention and diagnosing the immune status (in vivo). They are
produced by cultivation of microorganism strains and eukaryotic cells,
extraction of substances from biological tissues, including tissues of
human, animals and plants (allergens), and methods of genetic
engineering, hybrid technologies, reproductions of alive agents in
embryos or animals.
(Resolution of the CMU No 73; Order of the MOH No. 426 (as amended by
Order No. 3)

15. Biosimilars in Ukrainian legislation
 Similar biological medicinal product (biosimilar) is a biological medicinal
product which efficacy, safety and quality are similar to those of
registered reference biological product which patent protection has
expired. Similarity of therapeutic efficacy, safety and quality of such
medicinal product to those of the reference medicine should be
confirmed with respective pre- and clinical studies.
(Order of the MOH No 426 (as amended by Order No 3)

16. Biosimilars in Ukrainian legislation
Special requirements to biosimilars are introduced :
In case of registration of similar biological products (biosimilars) that
cannot be considered generics due to the specificity of the manufacturing
process, raw materials used, characteristics of the molecular structure and
therapeutic effects, in addition to Modules 1, 2, and 3 additional data are to
be provided to support the appropriate level of safety (toxicological or other
preclinical studies) and efficacy (clinical trials) (Chapter 3, Section Х of this
Procedure)
(paragraph.6.6 of Section VI, Chapter 3 of Section Х, Order of the MOH No
426 (as amended by Order No 3))

17. Biosimilars in Ukrainian legislation
New chapter “Special requirements for the registration dossier materials of
similar biological medicinal products (biosimilars)” has been added
When applying for registration of a similar biological medicinal product after
the expiration of the patent protection of data relating to the original
biological product registered before, the following materials are to be
provided:
information submitted should not be limited to Modules 1, 2 and 3
(pharmaceutical, chemical and biological data), supplemented with
bioequivalence and bioavailability data. The type and amount of additional
data (i.e., toxicological and other preclinical and relevant clinical data) shall
be determined in each individulal case in accordance with the relevant
requirements and guidelines;

18. Biosimilars in Ukrainian legislation
New chapter “Special requirements for the registration dossier materials of
similar biological medicinal products (biosimilars)” has been added
due to the diversity of biological medicinal products it may be necessary to
provide information on the identification studies provided for in Modules 4
and 5 of the registration dossier, with due regard being had to the special
characteristics of each medicinal product.
If the original medicinal product registered has more than one therapeutic
indication, the efficacy and safety of a similar biological medicinal product
shall be confirmed or, if necessary, demonstrated individually for each of
the claimed indications.

19. STATE CONTROL OF MEDICINAL
PRODUCTS

20. Main Regulations
 Resolution of the Cabinet of Ministers of Ukraine No. 73 “On Approval of
the Regulation on the Control of Conformity of Immunobiological
Products Used in Medical Practice with the Requirements of National
and International Standards” of January 15, 1996;
 Resolution of the CMU No 902 “On Approval of the Procedure for State
Quality Control of Medicinal Products Imported to Ukraine” of
September 14, 2005;
 Procedure for State Quality Control of Medicinal Immunobiological
Rroducts that are Used, Manufactured or Proposed for Use in Medical
Practice in Ukraine approved by Order of the MOH No 486 of December
06, 2001

21. State Control Procedure
 State control is mandatory for all products both domestic and foreign
manufacture that are used, manufactured or proposed for use in medical
practice in the territory of Ukraine.
 Control is carried out by expert evaluation of the materials of the
(manufacturer's) quality control of the product batches (protocols of
batch quality control, analytical reports) and laboratory testing of the
product specimens in accordance with the specifications in the
prescribed form and with the established regularity of the state control.
 Conclusion on MIP quality conformance is a basis for further circulation
of the biolobical product, including its marketing.
Order of the MOH No 486

22. Form and Frequency of State Quality Control of MIPs
ConductedConducted based on:based on:
 whether the product is registered in Ukraine;whether the product is registered in Ukraine;
 use of the product in the state programs, includinguse of the product in the state programs, including the program ofthe program of
vaccination in Ukraine;vaccination in Ukraine;
 availability of a copy of an official document of compliance of theavailability of a copy of an official document of compliance of the
manufacture with GMP requirements issued by a competent authority ofmanufacture with GMP requirements issued by a competent authority of
Ukraine or Japan or a member country of Pharmaceutical InspectionUkraine or Japan or a member country of Pharmaceutical Inspection
Cooperation Scheme (PIC / S);Cooperation Scheme (PIC / S);
 Data of side and non-specific effects monitoringData of side and non-specific effects monitoring;;
 Data on stability of the qualityData on stability of the quality parametersparameters for the period of the productfor the period of the product
use in medical practice in Ukraine.use in medical practice in Ukraine.

23. Forms of State ControlForms of State Control
 Detailed quality control: control of all the batch qualityDetailed quality control: control of all the batch quality
parameters in accordance with the specifications and methodsparameters in accordance with the specifications and methods
of quality control;of quality control;
 SelectiveSelective quality control: control of selected quality parametersquality control: control of selected quality parameters
of the product batches.of the product batches.

24. Conclusion of MIConclusion of MIBBP quality conformance issued by theP quality conformance issued by the
Ministry of Health is a result of the state control ofMinistry of Health is a result of the state control of
the MIthe MIBBP batchP batch
Order of the MOH No 486 of December o6, 2001Order of the MOH No 486 of December o6, 2001
Resolution of the CMU No 73 of January 15, 1996Resolution of the CMU No 73 of January 15, 1996
Certificate of approval of a biological product issued by a
National authority on quality assurance for biological
products
WHO Technical Report Series, No.822, 1992 GuidelinesWHO Technical Report Series, No.822, 1992 Guidelines
forfor national authorities on quality assurance for biologicalnational authorities on quality assurance for biological
productsproducts
Procedure for state control of biological
products

25. Thank you
for attention!