drug approval system of uzbekistan

Drug approval system of Uzbekistan

Ibragimova Mukhabbat Yahyaevna

Head of department

Center of pharmaceuticals and medical devices policy

General Administration for Quality Control of Pharmaceuticals and Medical Equipment of Ministry of Health of Uzbekistan

August 2017 – Seoul/Osong

General information about Uzbekistan

• Location: Central Asia. It borders with the Republic of Kazakhstan, Turkmenistan,

Kyrgyzstan, Tajikistan and Afghanistan. Located between the rivers Amu Darya and Syr

Darya

• State territory: 448 900 км2

• Administrative-territorial division: 12 regions, autonomous republic of

Karakalpakstan and the capital Tashkent. Tourist cities - Samarkand, Bukhara and Khiva.

• Population: More than 32,000,000 people. More than 100 nations and nationalities. 80%

of Uzbeks, other Tajiks, Turkmens, Kazakhs, Russians, Koreans ... 51% of population live

in cities and 49% in rural areas. More than 60% of population is young people. The most

densely populated country in Central Asia (65.8 people per 1км2).

• History: More than 3000 years of statehood, it is located at the crossroads of the Silk Road.

This year will be 26 years of independence.

2

3

Legislation: Laws

• "On pharmaceuticals and pharmaceutical activities" dated 04/01/2016.

• "On denunciation of Agreement on Providing Population with Medicines, Vaccines

and Other Immunobiological Preparations, Medical Devices and Medical Equipment

Produced in Territory of the Member States of Commonwealth of Independent States

dated December 18, 2007.

• "On protection of citizens health" dated August 29, 1996

• "On narcotic drugs and psychotropic substances" dated 19.08.1999

• "On Sanitary and Epidemiological Well-being of the Population" dated August 26,

2015

• "On compulsory treatment of patients with chronic alcoholism, drug addiction or

substance abuse" dated 09.12.1992

4

Legislation: Presidential Decrees and Orders

• "On measures to support domestic manufacturers of pharmaceuticals and

medical products" dated 14.07.2006.

• "On measures to further improve provision of population with medicines and

medical products" dated October 31, 2016.

• "On Program of Measures for Further Development of Republic's

Pharmaceutical Industry for 2016-2020" dated 16.09.2016.

• "On measures to create favorable conditions for accelerated development of

pharmaceutical industry of Republic" dated April 20, 2017

• "On measures to further improve sale of medicines and medical products,

licensing of pharmaceutical activities" dated February 14, 2017

5

Legislation: Decrees and orders of Cabinet of Ministers of Uzbekistan

• "On approval of regulations on procedure for registration of pharmaceuticals and

medical products and issuance of registration certificate" dated December 22, 2014.

• "On measures to further improve tender sales" dated 14.09.2015.

• "On measures to further improve licensing of pharmaceutical activities" dated

12.05.2017.

• "On regulation of import of ready-made medicines" dated 25.02.2011

6

Privileges for local manufacturer

• Presidential Decrees №2911 dated 20.04.2017 "ON MEASURES TO CREATE

FAVORABLE CONDITIONS FOR ACCELERATED DEVELOPMENT OF

PHARMACEUTICAL INDUSTRY OF UZBEKISTAN" dated April 20, 2017

Until 2021, manufacturers of pharmaceutical products are exempt from income tax and payment of

customs duties, excise and VAT as per approved list

• Decrees of Cabinet of Ministers №49 dated 25.02.2011"ON REGULATION OF IMPORT OF

READY-MADE MEDICINES"

20% of VAT is levied for importing 67 medicines produced by local producers

• Inter-ministerial Decree No.1952 dated 08.05.2009 "ON APPROVAL OF LIST OF

IMPORTED RAW MATERIALS FOR PRODUCTION OF PHARMACEUTICALS AND

MEDICAL DEVISES, WHICH ARE EXAMPT FROM PAYMENT OF VALUE ADDED

TAX"

20% VAT on pharmaceutical raw materials is not collected according AS PER approved list

7

Pharmaceuticals Registration statistics

At the moment, 8557 medical products have been registered in Uzbekistan in 172 pharmacotherapeutic groups. Products of 72 groups do not have any local production

Quantity Share

Medicines of foreign countries 4 409 52%

Medicines of CIS 1 782 21%

Local medicines 2 366 28%

Total 8 557 100%

8

TOP 20 pharmacotherapeutic groups for registration

№ Pharmacotherapeutic group Foreign countries CIS Local Total

1 Antibiotic 664 222 400 1286

2 Non-steroidal anti-inflammatory drug 232 70 96 398

3 Antihypertensiveagent 223 70 80 373

4 Vitaminsandminerals 126 75 131 332

5 Expectorant 88 46 101 235

6 Antiviralagent 124 61 32 217

7 Agent for correction of metabolic processes 100 61 53 214

8 Antifungalagent 101 48 64 213

9 Antiallergicagent 102 38 53 193

10 Antitumoragent 153 30 1 184

11 Analgesic-antipyretic 90 43 45 178

12 Anti-inflammatoryagent 53 18 107 178

13 Antiseptic 15 25 131 171

14 Antiulcer 122 15 29 166

15 Glucocorticosteroid 84 45 18 147

16 Nootrop 45 54 31 130

17 Remedy for symptoms of ARI 90 6 33 129

18 Agentstimulatinghematopoiesis 97 4 28 129

19 Salinesolution 10 22 90 122

20 Agentfor treatment of ENT diseases 67 41 14 122

Total for the top twenty 2586 994 1537 5117

Pharmacotherapeutic groups with 10 or more registered foreign drugs and no any local production.

№ Pharmacotherapeutic group

Number of local

medicines Number of foreign medicines

1 Insulin products 36

2

Agents predominantly used in ophthalmology

34

3

Hormone pituitary, hypothalamus and their analogue

27

4 Oralcontraceptive 25

5 Immunodepressant 20

6 Agent against motion sickness syndrome

18

7 AcneRemedy 16

8 Remedy mainly used in dentistry 16

9 Tranquilizer 16

10 Angioprotector 12

11 Antihypoxant, antioxidantagent 12

12 Regulator of calcium-phosphorus metabolism

11

13 Cardiacglycoside 11

14 Narcoticanalgesic

10

15 Opioidanalgesic

9

10

List of molecules and forms which are not produced in Uzbekistan (1)

Pharmacotherapeutic group INN Forms

Insulin products Insulin glulisine, Insulin human, Insulin pigs, Insulin

detemir, Insulin lispro, Insulin aspart

Solution

Suspension

Agent predominantly used in

ophthalmology

Aminobenzoic acid, Hydrocortisone,

Phenilephrine, Emoxipine, Tetryzoline,

Dexpanthenol, Carbomer, Dexamethasone, Fusidic

acid, Hypromellose, Tobramycin, Potassium iodide,

Phenylephrinihydrochloridum,

Methylethylpiridinol, Ranibizumab

Drops

Ointment

Lyophilizate

Solution

Gel

Hormone pituitary,

hypothalamus and their analogue

Octreotide, Chorionicgonadotropin,

Somatropin, Urofollitropin, Follitropin,

Menotropin, Demoxytocin, Terlipressin

Solution

suspension

Lyophilizate

Oral contraceptive Desogestrel, Levonorgestrel, Ethinylestradiol,

Ulipristal, Lynestrenol

Tablets

Dragee

11



Immunodepressant

Etanercept, Tofacitinib, Ciclosporin

Leflunomide, Mycophenolatemofetil

Tacrolimus, Infliximab, Everolimus

Basiliximab

Lyophilizate Tablets

Capsules

Solution

Agents against motion sickness syndrome Betahistine, Dimenhydrinate Tablets

AcneRemedy Azelaiс acid, Zinc hyaluronate, Isotretinoin

Azelaic acid, Isotretinoin, Tretinoin

Cream, Suspension

Gel, Capsules

Remedy mainly used in dentistry Metronidazole

Benzidamine

Gel, Solution, Spray

Tranquilizer Afobazolum, Diazepam, Phenazepam, Hydroxyzine,

Alprazolam, Tofisopam, Hydroxyzine, Mebicar,

Oxazepam, Etifoxine

Tablets, Solution,

Capsules

12



Angioprotector Quercetin,Alprostadil,Ginkgo biloba,

Aesculushippocastanum L.

Gel, Tablets,

Granules, Capsules,

Solution

Antihypoxant, antioxidantagent Epinephrine, Phenylephrine, Norepinephrine

Solution

Regulator of calcium-phosphorus

metabolism

Calcium carbonate, Lanthanum carbonate,

Cholecalciferol, Calcitrol, Calcitonin

Tablets, Suspension,

Capsules, Solution,

Granules, Spray

Cardiacglycoside Digoxin, Corglycone, Quabain, G-Strophanthine

Tablets, Solution

Narcoticanalgesic Tramadol, Fentanyl, Flupirtine

Solution, Tablets,

Capsules

Opioidanalgesic

Tramadol, Morphine, Trimeperidine, Fentanyl

Solution

Tablets

13

Drugs Provision on Essential Medicines

•There are 437 medicines in essential medicines list. 55% of them are produced in the country and 45% are

imported

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LAW №399 dated 04.01.2016 “ON MEDICINES AND PHARMACEUTICAL ACTIVITIES” (1)

Article 3. Basic concepts

• Following basic concepts are used in this Law:

• Pharmaceuticals - remedy obtained on the basis of medicinal substances and auxiliary

substances; medicinal substances; drugs permitted for use in medical practice for

prevention, diagnosis and treatment of diseases, as well as for changing status and

functions of human body;

• Medicinal substances - substances of natural or synthetic origin, possessing

pharmacological, immunological or metabolic activity or used for diagnostic purposes,

permitted for use in medical practice;

• Medicines - dosed, packaged medicines ready for use;

• Medicinal plant raw materials - plants or its parts containing biologically active

substances used for manufactureing medicinal products;

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Article 12. State registration of pharmaceuticals, medical devices and medical equipment

• Pharmaceuticals, medical devices and medical equipment are permitted for use in medical practice after

their state registration.

• Following is subject to state registration:

Pharmaceuticals;

New combinations of pharmaceuticals registered in Uzbekistan;

Pharmaceuticals previously registered in Uzbekistan, but produced in other forms, dosages or by other

manufacturer;

Medical devices;

Medical equipment.

• State registration of pharmaceuticals, medical devices and medical equipment is carried out by Ministry of

Health of Uzbekistan.

• Registered pharmaceuticals, medical devices and medical equipment are included in State Register of

Pharmaceuticals, Medical Devices and Medical Equipment Permitted for Use in Medical Practice.

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• State registration of pharmaceuticals with different medicinal substances under the same trade

name is not allowed.

• Valid registration certificate is issued for a period of five years on the basis of state registration of

pharmaceuticals, medical devices and medical equipment.

• Validity of registration certificate may be extended at request of registration certificate holder

attaching necessary documents. Application for prolonging registration certificate validity must

be submitted within three months before expiration of its validity.

• After expiry of registration certificate validity, pharmaceuticals, medical devices and medical

equipment are permitted for sale and use in medical practice, provided they are produced during

period of validity of expired registration certificate.

• Registration certificate holder is required to inform Ministry of Health of Uzbekistan about new

data regarding safety, quality and effectiveness of pharmaceuticals, medical device and medical

equipment.

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Article 13. Pharmacovigilance

• Pharmacovigilance is an activity aimed at identifying, evaluating and

preventing adverse unintentional and unfavorable reactions for body

observed in humans when using pharmaceuticals in accordance with

instructions for its use.

• Treatment and prophylactic institutions, pharmacies and organizations

that produce, sell and use pharmaceuticals must inform Ministry of

Health of Uzbekistan in writing about all cases of detection of adverse

reactions in use of pharmaceuticals

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DECREE OF CABINET OF MINISTERS OF UZBEKISTAN №. 352 dated 22.12.2014 “ON APPROVAL OF REGULATION REGARDING REGISTRATION OF PHARMACEUTICALS AND

MEDICAL DEVICES (MD) AND ISSUANCE OF REGISTRATION CERTIFICATE (RC)”

Structure

• I. General Provisions

• II. Permits and conditions

• III. Documents and samples

• IV. Regulations

• V. Changes and additions to RC

• VI. Re-registration and renewal of RC

• VII. Suspension and termination of RC

• VIII. Register of issued RC

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II. Permits and conditions

• Observance of legislative acts and normative documents;

• Providing comprehensive information on the reasons for making changes, their impact

on efficiency, safety and quality indicators;

• Mandatory regular notification to the General Administartionabout new data regarding

pharmaceuticals’ pharmacological efficacy and safety;

• Timely elimination of shortcomings indicated by experts

• Presenting samples of pharmaceuticals and medical devices and other materials in

prescribed time frame

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III. Documents and samples

• а) Applicationasper approvedform

• b)Copy of state registration certificate of business entity;

• c) Registration documents in duplicate;

• d)Samples of medecines (for three-time testing in three industrial series), standard

refference of substances, control materials of specific reagents and quality

certificates for them.

• Confidential information in documents should not be disclosed by the General

Administartion

21

IV. Regulations

• Registration fee for one pharmaceuticals is 6000 USD including VAT. For each additional dose of the same pharmaceuticals if submittet simultaneous with the same pharmaceuticals will cost 600 USD. This money will not be refunded.

• Approval and issuanceperiod of RC is a maximum of 180 working days from date of application receipt. This period does not include time spent by applicant to eliminate shortcomings (45 working days), to provide clinical trial programs and samples (45 working days), as well as duration of clinical trials.

• RC issuance fee –75 USD

• The General Administartion may conduct (independently or with involvement of third parties or independent experts) examination of registration documents, inspection checks, laboratory tests, pharmacological and toxicological studies, preclinical studies, bioequivalence testing.

22

Departments of the General Administartion involved in registration (1)

а) Registration department:

• Conducts primary examination of documents and materials;

• Makes correspondence with applicant;

• Concludes contract and issues invoice;

• Transfers documents for examination to State CenterLaboratory, PharmacologicalCommittee,

Pharmacopoeial Committee, Committee on New Medical Equipment and to Drug Control Committee;

b) State CenterLaboratory:

• Carries out examination of registration documents;

• Assesses regulatory documents, conducts tests to determine whether samples of medecine or medical

device meet requirements of regulatory documents;

• Transmits test reports, documents of medecine or medical device to Pharmacopoeia Committee,

Pharmacological Committee and Committee for New Medical Equipment;

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c) Pharmacopeia Committee:

• Conducts examination of registration documents, protocols of laboratory tests;

• Requires applicant to replace or include alternative methods, additional indicators and methods of analysis in regulatory documents, taking into account modern achievements of science and technology, as well as physical and chemical properties of active and auxiliary substances;

• Conducts re-examination of registration documents with involvement of independent experts;

• Sends samples and documents of medecine to State Center laboratory for additional tests in cases when it is impossible to reproduce methods of analysis, lack of its specificity, sensitivity and accuracy, as well as in case of amendments to regulatory documents that require testing of methods of analysis;

• Approves normative documents of pharmaceuticals and medical devices;

• Makes recommendations to Expert Council to register or refuse medicine;

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d) Pharmacological Committee:

• Conducts examination of administrative, pharmacological, toxicological and clinical parts of registration documents;


• Determines types of tests, approves relevant clinical bases for clinical trials, makes recommendations for clinical trial programdevelopment and approves them;

• Makes recommendations to Expert Council to register medecine with or without clinical trials or to refuseit;

• Approves instructions (leaflets) of medecines or changes to instaruction;

• Carries out pharmacological supervision;

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e) Committee on New Medical Equipment:

• Conducts examination of registration documents, protocols of laboratory analysis, clinical (medical) test materials;


• Based on specifics of medical devices, provides ts testing;

• Gives recommendations on development of clinical (medical) testing programs and coordinates clinical (medical) testing programs;

• Determines types of tests, approves relevant clinical bases for clinical (medical) testing;

• Controls clinical trials of medical devices;

• Approves instructions (manual) and labeling of medical devices or changes or additions to them;

• Prepares regulatory documents of medical devicesfor approval;

• Makes recommendations to Expert Council to register medical devices with or without clinical (medical) tests or to refuse registration for them;

26


f) The Drug Control Committee:

• Conducts examination of drug registration documents containing narcotic drugs, psychotropic

substances and precursors;

• When examining medicinal products containing narcotic drugs, psychotropic substances and

precursors, checks presence of these substances in state-controlled list of narcotic drugs,

psychotropic substances and precursors, checksif permission is obtained for their medical use,

whether it is prescription product and Makes proposals to Pharmacological and Pharmacopeia

Committees;

g) Pharmaceutical Inspection:

• Conducts inspection of production conditions and quality control;

• Issues certificate on availability of production and quality control conditions for appropriate type of

pharmaceuticals and medical devices;

• Inspection is carried out by decision of Expert Council, adopted on the basis of expert opinion of

Pharmacopoeia and Pharmacological Committees after examination of registration documents.

27

Expert Council

Expert Council on the basis of conclusions of Pharmacopoeia Committee,

Pharmacological Committee, Committee on New Medical Equipment,

and other departments of GeneralAdministration, within seven working

days, decides whether to give or refuse RC. Within a day General

Administration proves Expert Council decision.

28

The reason for refusal to issue RC may be the following: (1)

• Incomplete submission of documents, samples and other required materials;

Unconformity of applicant with permission requirements and conditions;

Inaccurate or distorted information in the documents;

Obtaining prooved negative conclusion on the basis of studies, inspections (surveys) or

other scientific and technical assessments, implementation of which is mandatory.

• Refusal to issue RC for other reasons, including for reasons of inexpediency, is not

allowed.

• A notice of denial of registration is issued in writing, indicating reasons for refusal,

specifying legislation and time limit (not less than 10 days) during which applicant,

after eliminated reasonsof denial, may submit documents for reconsideration. In this

case, the General Administration repeatedly reviews, within 10 days, relevant

documents certifying the elimination of reasons for refusal. Reconsidiration is free of

charge.

29

The reason for refusal to issue RC may be the following: (2)

• If elimination of reasons for refusal by applicant entails a change in the properties of pharmaceuticals and medical devices сoncerningto quality, efficiency and safety, application is deemed to be re-filed and reviewed by General Administration on general basis.

• When reconsidering documents, it is not allowed to General Administrationto bring reasons for refusal which were not previously stated in writing to applicant, except for bringing the reasons for refusal associated with documents certifying elimination of the previously mentioned reasons.

• The application for reconsidiration after expiry of time indicated in notice of refusal is considered to be submitted again and is considered by General Administrationon general basis

30

VI. Re-registration and renewal of RC

• In case of transformation of applicant’s business entity, change of its name or location,

without changing place of operation (postal address), the applicant or its legal successor

is obliged to submit to General Administrationapplication for re-registration of

RCattaching documents confirming specified information not later than seven working

days after above mentioned changes have happened.

• Application for extending the validity of RC with all necessary documents must be

submitted to General Administrationthree months before the expiration of RC validity.

• The cost of validity extension of RC for 5 years is 50% of registration fee.

• In case of loss or damage RC, a duplicate is issued at the request of applicant in 5 days.

• Cost for issuing RCduplicate is 50% of registration fee.

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VII. Suspension and termination of RC

• Single rude violation of permissive requirements and conditions, which gives grounds for RC termination are:

• Evasion of inspections of compliance with permissive requirements and conditions;

• Causing harm to life and health of citizens or creating real threat of causing such harm.

32

DOCUMENTS submitted for registration of medicinal products * (1)

Pharmaceuticals

Medicament substance

Medicinal

plant raw

materials

Homeopathi

c medicine МIBP

1 2 3 4 5 6 7

I. General Documentation

I Content

I A Administrative data

I A 1. Application according to approved form + + + + +

I A 2. Certificate of pharmaceutical product (CPP) issued in accordance with WHO recommendation

(notarized)

in case of absence: registration certificate in manufacturer country

+ - + + +

I A 3. GMP certificate (indicating date and results of last inspection) + + + + +

I A 4. Copy of license to carry out pharmaceutical activities

+ + + + +

I A 5. If several manufacturers participate in production process, documents of points IА2, IА3, IА4 are

submitted to all participants of production

+ + + + +

I A 6. License agreement (agreement) to manufacture (before the expiration of the patent for the original

drug)

+ - - + +

I A 7. Copy of patent (if any) + + + + +

I A 8. Document confirming quality of active substance (certificate of analysis from manufacturer,

certificate of conformity, protocol of analysis, analytical passport, entry control, etc.)

+ + + + +

I A 9. Document confirming quality of finished product of three industrial series (certificate of analysis,

protocol analysis, etc.)

+ + + + +

I A 10. Document on prion safety for substances of animal origin from manufacturer, certificate on absence

of spongiform encephalopathy of cattle (BSE/TSE)

+ + - + +

33


Pharmaceuticals

Medicamen

t substance

Medicinal

plant raw

materials

Homeopath

ic medicine МIBP

1 2 3 4 5 6 7

I. General Documentation

I A 11. Information on refusal to register, withdraw from market by competent authority or

applicant, on termination of validity of registration certificate or suspension by competent

authority (specifying reason in case of precedents)

+ + + + +

I B Brief description of the medicinal product (SmPC), labeling and instructions for use

I B 1. ** Brief description of the drug (SmPC) + - + + +

I B 2. Copy of instruction for use of medicinal product approved in country of manufacturer, draft

instruction for use in state and Russian languages

+ - + + +

I B 3. Models of packages and markings in color on paper and electronic media + + + + +

I C Detailed description of pharmacological surveillance and risk management system for

medical use of medicinal product proposed by applicant

+ - - + +

I D Document confirming availability of qualified person responsible for pharmacovigilance, for

collection and recording of adverse reactions detected in Uzbekistan

+ - + + +

I Е Reports of independent experts on chemical, pharmaceutical and biological documentation,

pharmaco-toxicological documentation, clinical documentation (information on main

properties of medecine)

+ - + + +

34


Pharmaceuticals

Medicam

ent

substanc

e

Medicina

l plant

raw

materials

Homeop

athic

medicine

МIBP

1 2 3 4 5 6 7

II. Chemical, pharmaceutical and biological documentation

II Content + + + + +

II A Composition

II A 1. Composition of pharmaceuticals + - + + +

II A 2. Packing (short description) + + + + +

II A 3. Pharmaceutical development (justification of composition, choice of

primary packaging, etc.)

+ - + + +

II B Method of manufacturing (scheme of technological process, draft of

technological regulations)

II B 1. Production formula + + + + +

II B 2. Manufacturing process + + + + +

II B 3. Control in production process (operational control) + + + + +

II B 4. Process validation + + + + +


Pharmaceuticals

Medicamen

t substance

Medicinal

plant raw

materials

Homeopathi

c medicine МIBP

1 2 3 4 5 6 7


II C Methods of control of raw materials * + + + + +

II C 1. Active substance *

II C 1.1. Normative documents (specifications and methods of quality control)* of active substances

+ + + + +

II C 1.2. Scientific data * + + + + +

II C 1.2.1. Nomenclature * + + + + +

II C 1.2.2. Description * + + + + +

II C 1.2.3. Production * + + + + +

II C 1.2.4. Quality control in production process (intermediate control) + + + + +

II C 1.2.5. Chemical development + + + + +

II C 1.2.6. Impurities * + + + + +

II C 1.2.7. Butch analysis* + + + + +

II C 1.2.8. Information on stability studies, reports and shelf life + + + + +

35


Pharmaceuticals

Medicame

nt substance

Medicinal

plant raw

materials

Homeopat

hic

medicine

МIBP

1 2 3 4 5 6 7


II C 2. Excipients

II C 2.1. Normative documents (specifications and established methods of quality control) of

auxiliary substances

+ - - + +

II С 2.2. Scientific data + - - + +

II С 2.3. Butch analysis*

II C 3. Packing material (inner / outer packaging) + + + + +

II C 3.1. Specifications and established methods for quality control of packaging materials and

quality certificates

+ + + + +

II C 3.2. Scientific data + + + + +

II D Methods for quality control of intermediate products + + + + +

II E Methods for quality control of final product

II E 1.

Specifications and methods of quality control with authentic translation into Russian + + + + +

II E 1.1. Regulatory document of pharmaceuticals + + + + +

II E 1.2. Standards information + + + + +

II E 1.3. Explanatory note to normative document + + + + +

II E 1.4.

When extending registration period, copy of approved normative document + + + + +

36


Pharmaceuticals

Medicame

nt substance

Medicinal

plant raw

materials

Homeopat

hic

medicine

МIBP

1 2 3 4 5 6 7


II E 2. Scientific data + + + + +

II E 2.1. Validation of analytical methods and comments, standards (working standards) + + + + +

II E 2.2. Butch analysis + + + + +

II F Stability

II F 1. Methods for stability studying + + + + +

II F 2. The results of stability test for at least 3 industrial or pilot (pilot) series (data and reports

of stress tests and long-term tests in real time)

+ + + + +

II G Information on dissolution profile (for solid dosage forms) + - - + +

II Н Data on bioavailability, bioequivalence (for generics), for parenteral forms of generics -

safety and efficacy data

+ - - + +

II K Control data on animals - - - - +

II L Data on likely environmental hazard for preparations containing genetically modified

organisms

+ + - - +

II M Periodicallyupdated Security Report + - + + +

II Q Additional information confirming quality + + + + +

37

Pharmaceuticals

Medicamen

t substance

Medicinal

plant raw

materials

Homeopath

ic medicine МIBP

III. Pharmacological and toxicological documentation

III Content + + + + +

III A

Toxicity with single administration and administration of repeated doses (acute, subacute,

chronic toxicity)

+ - - + +

III B Influence on reproductive function

Data on teratogenicity, gonadotoxicity and embryotoxicity

+ - - - +

III C * Data on mutagenicity + - - - +

III D * Data on carcinogenicity + - - - +

III Е Pharmacodynamics (specific action, general pharmacological properties (for medical

immunobiological preparations - reactogenicity, specific activity)

+ - - + +

III F Pharmacokinetics (absorption, distribution, metabolism, excretion) + - - - +

III G Data on bioequivalence (for generics), for MIBP - comparative characteristics + - - - +

III Н * Data on local irritant effects (for MIBP, including vaccines - immunogenicity) + - - - +

III K * Addiction to medecine and cumulative properties + - + - +

III L * Antigenicity + - - - +

III М Additional safety information + + + + +

IV. ** Clinical documentation

IV Content + + + + +

IV A Data on clinical pharmacology (pharmacodynamics, pharmacokinetics) (in vivo for

medical immunobiological preparations - data on epidemiological, clinical,

immunological efficacy)

+ - - + +

IV B Results of clinical trials, scientific publications, reports + - - + +

IV С Post-registration experience data (if any) + - - + +

IV D Additional information confirming effectiveness and safety, quality, clinical effectiveness

and safety and other additional information after registration

+ - - + + 38

Notes:

• *) The documents indicated in the list are required taking into account origin, properties, features of method of obtaining / producing medicinal products; If some parts of documentation are not included in registration dossier, reason should be indicated in appropriate place under appropriate title.

• **) If available.

• ***) For medicinal products of animal origin, following additional information should be provided in Section IIC1:

• Data on species, age, diet and geographic region of origin of animals from which raw materials are obtained;

• Data on nature (category) of tissue from which the raw material for production of medicinal product is derived, in terms of its danger with regard to content of prions;

• Technological scheme of processing raw materials with indication of extractants, temperature regime, etc..;

• Control methods of raw materials..

39

LIST of documents submitted for registration of medical device (1)

• 1. List of submitted documents.

• 2. Letter of attorney from manufacturer to person authorizing himto conduct the registration process.

• 3. General information about medical device.

• 4. Registration certificate of medical product (if medical device was previously registered).

• 5. Normative document that includes order and methods of testing medical device, standard for similar products.

• 6. For product of batch production, draft of organization’sstandard/ pharmacopeial article, technological regulations, technological instruction.

• 7. Passport for medical equipment, analytical passport for medical device.

• 8. Technical description of medical equipment.

40


• 9. Information on laboratory tests, technical tests, preclinical studies and clinical (medical) tests.

• 10. Test methods, programs and protocols (for sterile medical products - tests conducted in last year) on medical devices.

• 11. Information on compliance of medical device with international standards (if available).

• 12. Methods of verification of medical equipment (for measuring devices). • 13. Information on absence of infectious agents in "in vitro" - diagnostic tools

prepared from human blood. • 14. Information on stability in storage and transport of "in vitro" - diagnostic

tools. • 15. Illustrated promotional materials, brochures, catalogs, photo size not less

than 13 x 18 cm. • 16. Sample of medical device (in sufficient quantity for carrying out tests in

accordance with normative document).

10


• 17. Protocol of analyzes of presented series of medical products.

• 18. Colored graphic models of primary and secondary packaging.

• The above mentioned documents are submitted to General Administration in two copies.

• Copies of documents must be readable and certified with seal and signature of head of organization.

10

Thank you!

43