[Federal Register Volume 61, Number 245 (Thursday, December 19, 1996)]
[Notices]
[Pages 67036-67041]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-32188]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Memorandum of Understanding Revised Annex Between the Food and 
Drug Administration and the Russian Federation

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is providing notice of 
a Revised Annex to a Memorandum of Understanding Between the FDA and 
the Russian Federation. The purpose of the Revised Annex is to reaffirm 
their cooperation under the principles of cooperation established in 
the MOU initially

[[Page 67037]]

effective February 15, 1994, and to clarify and expand the procedures 
for registration under this MOU. The purpose of the initial MOU is to 
exchange information on drugs and biological products and to facilitate 
the development of the Russian health care sector by establishing in 
Russia a streamlined registration procedure for U.S. drugs and 
biological products.

DATES: The agreement became effective January 30, 1996.

FOR FURTHER INFORMATION CONTACT: Philip M. Budashewitz, Office of 
Health Affairs (HFY-50), Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857, 301-827-4480.

SUPPLEMENTARY INFORMATION: In accordance with 21 CFR 20.108(c), which 
state that all written agreements and memoranda of understanding 
between FDA and others shall be published in the Federal Register, the 
agency is publishing notice of this memorandum of understanding.

    Dated: December 11, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.

Statement on the Revised Annex to the Memorandum of Understanding 
Between the Food and Drug Administration Department of Health and Human 
Services and the Ministry of Health and Medical Industry of the Russian 
Federation and the State Committee for Sanitary and Epidemiological 
Surveillance of the Russian Federation Concerning Cooperation and 
Information Exchange on Drugs and Biological Products Facilitating 
Importation

    In order to reaffirm their cooperation under the principles of 
cooperation established in the Memorandum of Understanding (MOU) 
between the parties initially effective on February 15, 1994, and to 
clarify and expand the procedures for registration under this MOU, 
the following revisions are agreed to and become effective upon 
signature by representatives of the parties.
    The following revised Annex I is incorporated into the 
Memorandum of Understanding and replaces the original Annex I. This 
revised Annex I is the authoritative description of the procedures 
and requirements for the registration in the Russian Federation of 
products and substances manufactured in the United States under the 
jurisdiction of the U.S. Food and Drug Administration.
    The additional Annex II constitutes guidelines from the 
Pharmacopeial Committee of the Ministry of Health and Medical 
Industries relating the types of information expected to be 
submitted by firms in the Methods of Analysis and Specifications 
section of the Application described in Addendum 2 of Annex I.
    These Annexes will be made available to firms covered by this 
Memorandum for their guidance from the Ministry of Health and 
Medical Industries of the Russian Federation, the U.S. Food and Drug 
Administration, and the U.S. and Foreign Commercial Service, Moscow.

Points of Contact for Annexes I and II

    In order to facilitate the registration of pharmaceuticals and 
substances, the following additional contacts under the Memorandum 
of Understanding are adopted and appended to those specified in the 
original documents effective in February, 1994.
For the Food and Drug Administration
    Director
    Division of Drug Labeling and Nonprescription Drug Compliance
    Center for Drug Evaluation and Research (HFD-310)
    (Currently Bradford W. Williams)
    Food and Drug Administration
    7520 Standish Place
    Rockville, MD 20855
    U.S.A.
    Telephone: 301-594-0063
    Fax: 301-594-0165
For the Ministry of Health and Medical Industry
    Chief of Inspection
    State Control Inspection of Pharmaceuticals and Medical 
Technology
    (Currently Ramil U. Khabriev)
    Ministry of Health and Medical Industry of the Russian 
Federation
    Rakhmanovsky per. 3
    101431 Moscow
    Russian Federation
    Telephone: 7095-927-2875
    Fax: 7095-925-0128
    Done at Washington, D.C. on the 30th of January, 1996

For the Department of Health and Human Services of the United States of 
America:

Donna E. Shalala

For the Food and Drug Administration of the United States of America:

Mary Pendergast

For the Ministry of Health and Medical Industry of the Russian 
Federation:

Alexander Tsaregorodtsev

For the State Committee for Sanitary and Epidemiological Surveillance 
of the Russian Federation:

Gennady Onischenko

Revised Annex I

Instructions and Requirements for Registration in the Russian 
Federation of Pharmaceuticals and Substances Produced in the United 
States under the Jurisdiction of the U.S. Food and Drug 
Administration

    The following instructions establish the system and organization 
for registration in the Russian Federation of pharmaceuticals and 
substances (active substances) produced in the United States of 
America under the jurisdiction of the U.S. Food and Drug 
Administration (hereinafter referred to as the ``FDA'') in 
accordance with the Memorandum of Understanding between the parties.

Registration

    These instructions are mandatory for manufacturers and/or their 
authorized representatives seeking registration or re-registration 
of pharmaceuticals and substances produced in the U.S. under the 
jurisdiction of the FDA.
    All pharmaceuticals and substances registered in the Russian 
Federation must be registered in the name of their manufacturer and/
or in the name of their authorized representative. In addition, the 
pharmaceutical or substance must be registered and listed with the 
FDA by the manufacturer.
    The registration will be conducted in accordance with the form 
specified in addenda 1 and 2.

1. General Regulations

        According to the existing laws of the Russian Federation, 
all pharmaceuticals (substances) may only be purchased for medical 
purposes after they have been registered in accordance with the 
established system of the Ministry of Health and Medical Industries 
of the Russian Federation.

2. Procedure for the Evaluation of Applications for Registration of 
Pharmaceuticals and Substances Produced in the U.S. under the 
Jurisdiction of the U.S. Food and Drug Administration.

    2.1 A manufacturer (applicant), hereinafter referred to as 
``Company'', that wishes to register a pharmaceutical (substance) in 
the Russian Federation must submit one (1) copy of a package in 
English and three (3) copies of the same package in the Russian 
language consisting of the following: a letter of intent (see 
Addendum 1), an application (see Addendum 2), and the appropriate 
documentation (specified in Addendum 1) for the pharmaceutical (or 
substance) to the Chief of Inspection, State Control Inspection of 
Medicaments and Medical Technology, hereinafter referred to as 
``Inspection on State Control.''
    2.2 Inspection on State Control will then forward the documents 
to:
    - the Bureau of Registration of Pharmaceuticals, Medical 
Technology, and Medical Substances, hereinafter referred to as 
``Bureau of Registration'' one copy of the complete application in 
Russian and the English copy (file);
    - the State Pharmacological Committee, hereinafter referred to 
as ``Pharmacological Committee'': one complete copy of the 
application in Russian and one sample of the pharmaceutical;
    - the State Pharmacopeial Committee, hereinafter referred to as 
the ``Pharmacopeial Committee'': one complete copy of the 
application in Russian and one sample of the pharmaceutical.
    2.3 The Pharmacological Committee will make a preliminary 
evaluation of the application and will meet within thirty (30) days 
of its receipt of the documents.
    2.4 The Pharmacological Committee or its Presidium will meet on 
the application

[[Page 67038]]

and the minutes of the meeting of the Pharmacological Committee or 
its Presidium will be signed by the Chairman of the Committee and 
the Academic Secretary; the decision will be confirmed by the Head 
of the Inspection on State Control. Copies of the minutes will be 
signed by the Chairman of the Pharmacological Committee or the 
Academic Secretary and forwarded to the Inspection on State Control, 
the Company and the Pharmacopoeial Committee within five (5) days of 
the confirmation of the minutes. The Pharmacological Committee and 
the Inspection for State Control will complete the step described in 
2.3 and 2.4 within thirty five (35) days from the submission of the 
application to the Inspection on State Control by the Company.
    2.5 The Pharmacopoeial Committee will complete its evaluation of 
the application for the pharmaceutical (or substance) within thirty 
(30) days of its receipt of the documents.
    2.6 Recommendations for registration will be made by the 
Presidium of the Pharmacopoeial Committee and a Declaration of the 
decision will be issued.
    2.7 This Declaration will be signed by the Chairman of the 
Pharmacopoeial Committee and the Academic Secretary; the decision 
will be confirmed by the Head of the Inspection on State Control 
within five (5) days after the meeting of the Pharmacopoeial 
Committee. The Pharmacopoeial Committee and the Inspection for State 
Control will complete the step described in 2.6 and 2.7 within 
thirty five (35) days from the submission of the application to the 
Inspection on State Control by the Company.
    2.8 The Inspection on State Control cannot guarantee timeless in 
regard to the evaluation of documents, if the documents are not 
complete or in accordance with the appropriate list.
    2.9 The Inspection on State Control has the right to suspend 
consideration of the application for registration of the 
pharmaceutical (substance) if the Company does not answer questions 
of the Pharmacological Committee or the Pharmacopeial Committee due 
to an incomplete application within ninety (90) days. In this case, 
the documentation provided by the Company and any registration 
fee(s) will not be returned to the Company. The Company will be 
notified of this suspension in writing within ten (10) days of the 
decision.
    2.10 All decision to be made by the Pharmacological Committee, 
Pharmacopeia Committee, and the Inspection on State Control will be 
in accordance with the terms of the Memorandum of Understanding 
between the parties.

3. Procedure for the Registration of Pharmaceuticals and Substances 
produced in the United States under the Jurisdiction of the U.S. 
Food and Drug Administration.

    3.1 The Bureau of Registration will, on the basis of the 
authorization of the Inspection on State Control, within five (5) 
days, issue an official Certificate of Registration (see Addendum 7) 
for manufacturers or Certificate of Registration and forward it to 
the Head of the Inspection on State Control for signature.
    3.2 The Bureau of Registration will send the issued Certificate 
of Registration to the Company and simultaneously will send copies 
to the Inspection on State Control, the Pharmacological Committee, 
and the Pharmacopeial Committee. The Bureau of Registration will 
send the Certificate of Registration to the Company within ninety 
(90) days of the submission of the application to the Inspection on 
State Control by the Company.
    3.3 The Certificate of Registration is valid for five (5) years 
with the option for re-registration (as provided in section 5 below) 
when the term has expired.
    3.4 The Pharmacopoeial Committee shall distribute the normative 
documents to the State Scientific Research Institute within ten (10) 
days after registration and to all other organizations who implement 
quality control of medical preparations and substances within sixty 
(60) days after registration.

4. The System of Changing and Supplementing the Application

    4.1 In order to change or supplement an application, the Company 
must send a supplemental application (see Addenda 7 and 9) 
describing the change being made and confirming the necessity to 
change or supplement the documentation. These supplemental 
applications should be provided as follows: three (3) copies in 
Russian and one (1) copy in English.
    4.2 The Inspection on State Control will then forward the 
documents to:
    - the Bureau of Registration - one (1) Russian language Copy and 
one (1) English language copy
    - the Pharmacological Committee - one (1) Russian language copy
    - the Pharmacopoeial Committee - one (1) Russian language copy
    4.3 The Pharmacological and Pharmacopoeial Committees will 
within sixty (60) days, according to the established system of the 
meetings of their Presidiums, decide on the expediency of the 
changes and supplements and will in turn inform the Inspection on 
State Control of their decisions any changes or supplements which 
have been approved by the FDA will be accepted according to the 
terms of the MOU.
    4.4 The Inspection on State Control will inform the Company and 
the Bureau of Registration of the accepted decision in writing with 
in ninety (90) day of the submission of the application of the 
application to the Inspection on State Control by the Company.

5. The System of Re-Registering Pharmaceuticals (Substances).

    5.1 The re-registration of pharmaceuticals (substances) is 
undertaken when the validity of the registration has expired after 
five (5) years. For re-registration of the pharmaceutical, the 
Company should submit a written letter of intent (see Addendum 1) 
and documentation in accordance with Addendum 8 or 9.
    5.2 Re-registration is undertaken according to sections 4.2, 4.3 
and 4.4 of the present instructions.
    5.3 A document confirming the re-registration (Addendum 11) is 
sent to the Company within ninety (90) days of the submission of the 
re-registration application to the Inspection on State Control by 
the Company.

Revised Annex I

Addendum I

Letter of Intent/Application for Pharmaceutical (Substances) under 
the Jurisdiction of the FDA

    Chief of Inspection,
    State Control Inspection of Pharmaceuticals and Medical 
Technology
    Ministry of Health and Medical Industry of the Russian 
Federation
    3, Rakhmanovsky per.
    Moscow, 101431, Russian Federation
    With the present letter, the company ____________________ 
informs of its intent to register/re-register in the Russian 
Federation a pharmaceutical (or substance), produced by the company 
______________________________. The given pharmaceutical (or 
substance) is ____________________ (include form). The above 
pharmaceutical (or substance) is produced in the United States of 
America and is subject to the jurisdiction of the U.S. Food and Drug 
Administration, is freely marketed in the United States, and is 
manufactured in accordance with all U.S. Current Good Manufacturing 
Practice regulations. All information provided in this application 
is truthful, accurate and complete to the best of our knowledge.
    This letter contains the following attachments:
    1.1 The Application (Addendum 2) for the registration/re-
registration of the pharmaceutical (or substance)-three (3) copies 
in Russian and one (1) copy in English;
    1.2 One copy in English of the letter of approval from the Food 
and Drug Administration and a Russian translation (3 copies); OR
    For products subject to an FDA Over-the-Counter (OTC) monograph, 
one (1) copy in English and three (3) copies of a Russian 
translation of the relevant sections of the Final Monograph or 
Tentative Final Monograph with a Certification by the firm (in 
Russian) that the product conforms in all respects to the Final 
Monograph or Tentative Final Monograph.

[[Page 67039]]

    1.3 For each type of pharmaceutical, additional information as 
provided in the Addenda specified:
    - For drug products subject to a U.S. New Drug Application 
approved by FDA: Addendum 3.
    - For Prescription Generic Drug Products approved by the FDA: 
Addendum 4
    - For Substances: Addendum 5
    - To supplement to report changes: Addendum 7
    - To re-register when no changes have occurred: Addendum 8
    - To re-register when changes have occurred: Addendum 9
    1.4 Samples of the pharmaceutical in the proposed packaging 
form: five (5) samples for pharmaceuticals, two (2) for substances.
    Signature
    Corporate Seal
    (This letter should accompany each pharmaceutical or substance 
with the signature of the authorized official of the Company).

Revised Annex I

Addendum 2

Application

Application for the Registration of Pharmaceutical Products and 
Substances under the Jurisdiction of the FDA

    1. Manufacturing Company and address of the manufacturing 
facility
    2. Holder of the patent(s), if any exist, Expiration Date of the 
patent(s)
    3. Name of the pharmaceutical preparation
    4. International non-proprietary name (INN)
    5. Main synonyms of the preparation
    6. Composition of the preparation
    7. Therapeutic class
    8. Medical form
    9. Dosage of the preparation (quantitative)
    10. Route of administration (oral, injectable, etc.)
    11. Authorized indications and instructions for use
    12. Shelf life (expiration dating) and storage requirements
    13. Description of standard package form, including copies of 
all labels and labeling
    14. For a substance, the product(s) in which it is to be used
    15. Methods of analysis and release specifications: Guidelines 
on documentation are contained in Annex II.
    16. Most recent FDA-483 Notice of Investigational Observations.
    17. The name, address, telephone number, facsimile number, and 
the internet e-mail address (if any) of firm's authorized 
representative(s) AND IN THE CASE OF A DISTRIBUTOR REPRESENTING A 
MANUFACTURER:
    18. Notarized Letter from Manufacturing Company under corporate 
seal authorizing distribution company to distribute and register 
products (substances) in the Russian Federation.
    19. Complete labels and labeling for distributor shall be 
submitted if different than that of the manufacturer. In all cases, 
Distributor's labels and labeling must bear names and addresses of 
both manufacturing and distributing firms in the form ``Distributed 
by ______'', ``Manufactured by ______________''
    Signature
    Corporate Seal
    NOTE: For substances, items 8, 9, 10 and 12 do not apply.

Revised Annex I

Addendum 3

Documents Necessary for the Registration of New Pharmaceuticals 
under the Jurisdiction of the U.S. Food and Drug Administration

    1. A Summary (expert report) of results of pre-clinical and 
clinical studies of the pharmaceutical. This report must include a 
collection of general information concerning the pharmaceutical made 
up of short summaries of each of the following points:
    A. Pharmacological report (specifications) supporting all 
indications for usage as stated in the instructions, including 
summary of the pivotal clinical trial(s)
    B. Toxicology report (acute, subacute, subchronic, and chronic 
toxicology)
    C. Specific activity report related to the following: side 
effects, birth defects, allergies, skin irritations
    2. In a short summary of information on use of the 
pharmaceutical in clinical conditions and after FDA approval. A copy 
of any scientific publications concerning the pharmaceutical should 
be submitted.
    3. A short summary of information about side effects of the 
pharmaceutical and any adverse experiences with the pharmaceutical 
learned since FDA approval.

Revised Annex I

Addendum 4

Documentation Necessary for the Registration of Generic 
Pharmaceuticals under the Jurisdiction of the U.S. Food and Drug 
Administration

    1. A summary of bioequivalence study and results.

Revised Annex I

Addendum 5

Documentation Necessary for the Registration of Substances under 
the Jurisdiction of the U.S. Food and Drug Administration

    1. Certificate of Analysis for the substance from the 
manufacturing company (original copy or notarized copy).

Revised Annex I

Addendum 6

Sample Registration Certificate for Pharmaceuticals (Substances) 
under the Jurisdiction of the FDA

Ministry of Health Care and Medical Industries of the Russian 
Federation

Registration Certificate

No. ______________________________
This certificate has been issued to ______________________ (company-
producer, country) and testifies that in accordance to the 
regulations for registration of pharmaceuticals in the Russian 
Federation ____________________ (name of pharmaceutical (substance)) 
in the medical form ____________________ has been registered in the 
Russian Federation.
This certificate is valid for five (5) years and does not serve as 
an obligation to purchase the above mentioned pharmaceutical.
____________________
Date of Registration
Head of the Inspection on State Control or Pharmaceuticals and Medical 
Equipment
Bureau of Registration of Pharmaceuticals, Medical Equipment, and 
Products with Medicinal Value

Revised Annex I

Addendum 7

Supplemental Application to Report Changes for Pharmaceuticals 
(Substances) under the Jurisdiction of the FDA

    A special supplemental application is necessary to report any 
changes to the original registration application within 30 days of 
occurrence of the changes.
    1. Letter from Manufacturer (``Company''), under corporate seal, 
submitting information on any changes in the information submitted 
at the last registration, including any changes in FDA approved 
labels or labeling.

Revised Annex I

Addendum 8

Application for Re-registration (Renewal) of Pharmaceuticals 
(Substances) Subject to the Jurisdiction of the U.S. Food and Drug 
Administration when No Changes Have Been Made Since the Original 
Registration.

    1. Letter of Intent to Re-register - see Addendum 1.
    2. Letter from Manufacturer (``Company'') certifying that no 
changes in ingredients, labeling or Good Manufacturing Practice 
status have occurred since the time of the last registration.
    Signature
    Corporate Seal

Revised Annex I

Addendum 9

Application for Re-registration (Renewal) of Pharmaceuticals 
(Substances) Subject to the Jurisdiction of the U.S. Food and Drug 
Administration to Report Concomitant Changes

    1. Company-applicant
    2. Name of the pharmaceutical preparation
    3. Main synonyms of the preparation
    4. Composition of the preparation
    5. If changes have occurred in the ingredients or manufacturing 
procedure since the time of the original registration, indicate 
changes
    6. Medical forms
    7. Dosage of the preparations
    8. Administration (oral, injectable, etc.)
    9. Main indications for administration

[[Page 67040]]

    10. Shelf Life (expiration dating) and storage requirements
    11. Description of standard package form and copies of all 
labeling
    Signature
    Corporate Seal

Revised Annex I

Addendum 10

Sample Re-registration Certificate for Pharmaceutical (Substances) 
under the Jurisdiction of the FDA

Confirmation of the Re-registration of a Pharmaceutical(Substance)

The Inspection on State Control of Pharmaceuticals and Medical 
Equipment confirms that: ____________________ (name of 
pharmaceutical(substance)) has been registered as of __________ 
(date of registration) as number __________ (reg.number) and retains 
its registration number until the next routine re-registration.
In the event that the company-producer changes the composition of 
the pharmaceutical, the indications and warnings for usage or the 
methods of control and technological production, the company-
producer is obliged to inform the Inspection on State Control of 
Pharmaceuticals and Medical Equipment of such changes.
No. ________________ (registration number)
______________ (date of registration)
Head of the Inspection on State Control of Pharmaceuticals and Medical 
Equipment
Bureau of Registration of Pharmaceuticals, Medical Equipment, and 
Products with Medicinal Value

Annex II

Addendum 1

Supplemental Requirements when Appropriate for Submission of 
Methods of Analysis and Release Specifications in Applications for 
Synthetic Chemical Compounds (substances) for Registration in the 
Russian Federation

    Where appropriate for the substance submitted:
    1. Description of material (appearance)
    2. Identification test(s)
    3. Solubility
    4. Flash point/evaporation point
    5. Melting point and Boiling point
    6. Specific gravity/density
    7. Specific rotation
    8. Absorbance test (Specific Absorbance)
    9. Refractive index
    10. Clarity and color of solution
    11. Impurity(ies) test(s) (Chromatographic Profile)
    12. pH test
    13. Chlorides test
    14. Sulphates test
    15. Loss on drying
    16. Water contents assessed by Carl Fisher titration (include 
weight tested)
    17. Residual solvents test
    18. Heavy metals test
    19. Assay
    20. Microbiological tests
    21. Residue on Ignition

Annex II

Addendum 2

Supplemental Requirements when Appropriate for the Submission of 
Methods for Analysis and Release Specifications in Applications for 
Liquid Injection Dosage Form Products for Registration in the 
Russian Federation

    Where appropriate for the product submitted:
    1. Description (appearance)
    2. Identification test
    3. Transmittance/Absorbance test
    4. Particle size (in cases of suspension, emulsion)
    5. Solution pH
    6. Specific rotation
    7. Specific gravity/density
    8. Impurity(ies) test(s) (Chromatographic Profile)
    9. Net contents test/Deliverable Volume
    10. Pyrogen test(L.A.L. test)
    11. Sterility testing
    12. Completeness of solution and particulate test
    13. Clarity and color of solution
    14. Assay

Annex II

Addendum 3

Guidelines on Information Appropriate for Submission of Methods for 
Analysis and Release Specifications in Applications for Solid 
Dosage Forms for Preparation of Injections and Antibiotics for 
Registration in the Russian Federation

    Where appropriate for the product submitted:
    1. Description (appearance)
    2. Solubility
    3. Net contents test
    4. Identification test
    5. Melting range
    6. Specific rotation
    7. Specific absorbance
    8. Completeness of solution and particulate test
    9. Impurity(ies) test(s) (Chromatographic Profile)
    10. pH test
    11. Chlorides test
    12. Sulphates test
    13. Loss on drying
    14. Water test determined using Carl Fisher titration
    15. Heavy metals
    16. Pyrogenicity tests (chemical test)
    17. Test for sterility
    18. Assay
    19. Uniformity of Dosage Units
    20. Clarity and color of solution

Annex II

Addendum 4

Supplemental Requirements when Appropriate for the Submission of 
Methods for Analysis and Release Specifications in Applications for 
Liquid Ophthalmic Dosage Form Products for Registration in the 
Russian Federation

    Where appropriate for the product submitted:
    1. Description (appearance, color, clarity, particulate matter)
    2. Identification test
    3. Impurity(ies) test(s) (Chromatographic Profile)
    4. Transmittance/Absorbance test
    5. Viscosity (for solutions containing methyl cellulose or 
similar substances)
    6. pH test
    7. Determination of fill volume (method and allowable 
deviations)
    8. Sterility test
    9. Assay
    10. Particulates count- clear liquids
    11. Particle size- suspensions

Annex II

Addendum 5

Supplemental Requirements when Appropriate for the Submission of 
Methods for Analysis and Release Specifications in Applications for 
Liquid Dosage Forms for Internal and External Use Products for 
Registration in the Russian Federation

    Where appropriate for the product submitted:
    1. Description (appearance, color)
    2. Identification test
    3. pH test
    4. Specific gravity/density
    5. Viscosity
    6. Particle size test (in cases of suspension, emulsion)
    7. Net contents test
    8. Assay
    9. Microbiological purity test(s)
    10. Impurity(ies) test(s) (Chromatographic Profile)

Annex II

Addendum 6

Supplemental Requirements when Appropriate for the Submission of 
Methods for Analysis and Release Specifications in Applications for 
Aerosol Dosage Forms for Registration in the Russian Federation

    Where appropriate for the product submitted:
    1. Description
    2. Container integrity test
    3. Pressure test
    4. Assay
    5. Uniformity of delivered dose
    6. Net contents test and number of doses in container (for dosed 
aerosols)
    7. Percent total volume delivered
    8. Aerosol particle size test
    9. Identification test
    10. Water content test (method and allowable limits)
    11. Impurity(ies) test(s) (Chromatographic Profile)
    12. Microbiology purity (description of test or reference to 
Pharmacopeia)

[[Page 67041]]

Annex II

Addendum 7

Supplemental Requirements when Appropriate for the Submission of 
Methods for Analysis and Release Specifications in Applications for 
Tablets and Dragee Dosage Form Products for Registration in the 
Russian Federation

    Where appropriate for the product submitted:
    1. Description (appearance, color of tablets, appearance in 
fracture, size of tablets, diameter and height, strength)
    2. Average mass of tablets, method, allowable deviations
    3. Identification test
    4. Impurity(ies) test(s) (Chromatographic Profile)
    5. Insoluble Ash test (HCl)
    6. Disintegration test (method)
        AND/OR
    7. Dissolution test
          OR
      Release rate test
    8. Uniformity of Dosage Units test/Content uniformity test
    9. Assay
    10. Microbiology purity test(s)

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    ``Requirement #8 shall apply for tablets in which proportion of 
active ingredient in one tablet amounts to 50 mg or less.

Annex II

Addendum 8

Supplemental Requirements when Appropriate for the Submission of 
Methods for Analysis and Release Specifications in Applications for 
Solid Oral Capsule Dosage Form Products for Registration in the 
Russian Federation

    Where appropriate for the product submitted:
    1. Description of capsule and its contents (appearance, form, 
color)
    2. Identification test
    3. Average weight of capsule contents/weight variation test 
(method and allowable deviations)
    4. Disintegration test (method and norms)
        AND/OR
      Dissolution test
          OR
      Rate of Release test
    5. Uniformity of Dosage Units test/Content uniformity
    6. Solubility test
    7. Assay
    8. Microbiology purity test
    9. Impurity(ies) test(s) (Chromatographic Profile)

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    Requirements 5 and 6 apply to capsules in which proportion of 
active ingredient per one capsule amounts to 50 mg. or less.

Annex II

Addendum 9

Supplemental Requirements when Appropriate for the Submission of 
Methods for Analysis and Release Specifications in Applications for 
Suppository Products for Registration in the Russian Federation

    Where appropriate for the product submitted:
    1. Description (appearance, color, form, diameter, homogeneity)
    2. Average weight of dosage unit test
    3. Identification test
    4. Melting point or measuring full deformation time (lipophilic 
bases)
    5. Dissolution time (hydrophilic bases)
    6. Test for Uniformity of Dosage Units (Content Uniformity)
    7. Assay
    8. Microbiology purity test(s)
    9. Impurity(ies) test(s) (Chromatographic Profile)

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    Requirement 5 shall be observed for suppositories where 
proportion of active ingredient in one suppository amounts to 50 mg. 
or less.

Annex II

Addendum 10

Supplemental Requirements when Appropriate for the Submission of 
Methods for Analysis and Release Specifications in Applications for 
Topical Solid Products for External Use for Registration in the 
Russian Federation

    Where appropriate for the product submitted:
    1. Description (appearance, color)
    2. Identification test
    3. Net Contents test
    4. pH of aqueous extraction solution
    5. Uniformity of Dosage Unit test
    6. Particle size test (Size determination of drug particles)
    7. Sterility test(for eye ointments)
    8. Assay
    9. Microbiological purity tests
    10. Impurity(ies) test(s) (Chromatographic Profile)

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    Requirement 6 shall apply in accordance with the type of 
ointment.

Annex II

Addendum 11

Supplemental Requirements when Appropriate for the Submission of 
Methods for Analysis and Release Specifications in Applications for 
Tincture and Extract products for Registration in the Russian 
Federation

    Where appropriate for the product submitted:
    1. Alcohol test
    2. Description (appearance, color)
    3. Identification test
    4. Heavy metals
    5. Specific gravity/density.
    6. Residue on drying
    7. Net contents test
    8. Assay
    9. Moisture content test

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    NOTE: This Applies only to tincture and extract regulated as 
drug products.
    Medicinal Plants and Teas are not covered under this MOU.
[FR Doc. 96-32188 Filed 12-18-96; 8:45 am]
BILLING CODE 4160-01-F