[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