[Federal Register Volume 61, Number 247 (Monday, December 23, 1996)]
[Notices]
[Pages 67562-67565]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-32424]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Memorandum of Understanding Between the Food and Drug 
Administration and the Republic of Belarus

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is providing notice of 
a memorandum of understanding (MOU) between FDA and the Republic of 
Belarus. The purpose of the MOU is to exchange information on drugs and 
biological products and to facilitate the development of the Belarus 
health care sector by establishing in Belarus a streamlined 
registration procedure for U.S. drugs and biological products.

DATES: The agreement became effective March 25, 1996.

FOR FURTHER INFORMATION CONTACT: Bradford W. Williams, Office of 
Compliance, Center for Drug Evaluation and Research (HFD-310), Food and 
Drug Administration, 7520 Standish Pl., Rockville, MD 20855, 301-594-
0165.

SUPPLEMENTARY INFORMATION: In accordance with 21 CFR 20.108(c), which 
states 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.

224-96-4004

Memorandum of Understanding Between the Food and Drug Administration of 
the Department of Health and Human Services of the United States of 
America and the Ministry of Health of the Republic of Belarus on 
Cooperation and Information Exchange for Facilitating the Introduction 
of Drugs and Biological Products into the Republic of Belarus

    The Food and Drug Administration (FDA), of the Department of 
Health and Human Services of the United States of America, on the 
one hand; and the Ministry of Health of the Republic of Belarus, on 
the other hand, hereinafter referred to as the parties,
    Guided by principles recorded in the Agreement between the 
Government of the United States of America and the Government of the 
Republic of Belarus on Science and Technology Cooperation, signed in 
Minsk on January 14, 1994, and
    Strengthening the bonds of friendship between the parties, Have 
reached an understanding on matters of cooperation:

I

The goals of the parties are:
     1. To exchange information on drugs and biological products and 
on requirements applicable to them (including standardization, 
registration, quality control, and side effects), and prompt 
exchange of information on the removal of drugs and biological 
products from the market or restrictions on their use.
     2. To facilitate the development of the Belarusian health care 
sector by establishing in Belarus a streamlined registration 
procedure for United States drugs and biological products that are 
manufactured and marketed in the United States under the 
jurisdiction of the FDA as provided in the Annexes to this 
Memorandum of Understanding. The Belarusian party should use the 
streamlined procedure for such products.
    The parties confirm that it would be mutually beneficial for the 
parties to work together to streamline the process for registering 
in Belarus drugs and biological products when these products are 
permitted by the FDA to be marketed in the United States. The effect 
of the parties joint endeavors under this Memorandum of 
Understanding should be to extend to Belarusian users access to the 
same United States drugs and biological products as are available to 
United States users of such products, which possess a high degree of 
safety, effectiveness, and quality .

II

    This Memorandum of Understanding covers drugs and biological 
products manufactured and marketed in the United States under the 
jurisdiction of the FDA including:
    1. Drugs: articles that meet the definition of a drug under the 
United States Federal

[[Page 67563]]

Food, Drug and Cosmetic Act. Drugs include both prescription drugs 
and non prescription drugs (Over-the-Counter, ``OTC'' products). 
This Memorandum of Understanding does not apply to homeopathic drugs 
or to vitamins, mineral or herbal products, or any other dietary 
supplements.
    2. Biological products: products that are regulated as 
biological products under the United States Public Health Service 
Act.

III

    1. The Belarusian party should identify the streamlined 
registration requirements for those drugs and biological products 
that are manufactured and marketed in the United States under the 
jurisdiction of the FDA.
    2. For drugs and biological products that are manufactured and 
marketed in the United States under the jurisdiction of the FDA, the 
Belarusian party intends to accept the FDA's decisions and 
regulations on premarket approval, licensing, monographs, and 
related documentation, as well as FDA's quality standards and 
enforcement of manufacturing controls and other requirements.
    3. In addition to any requirements for registration as drugs, 
any products that can be defined as a controlled substance or highly 
addictive must receive the additional approval of the appropriate 
Belarusian bodies under the laws and regulations of the Belarus. 
Products for which this approval will be necessary should be further 
explained in an exchange of letters between the participants.
    This Memorandum of Understanding should apply equally to 
pharmaceutical or biological products manufactured and marketed in 
the United States under the jurisdiction of the FDA which require 
prescription prior to sale and those which are sold directly ``Over-
the-Counter'' (OTC) without prescription. It is understood that 
marketing status in the Republic of Belarus will be in accordance 
with Belarusian laws and regulations, notwithstanding United States 
marketing status.
    4. This Memorandum of Understanding lists, in Annexes, the 
information which the United States firms should provide to the 
Belarusian party on drugs and biological products that are 
manufactured and marketed in the United States under the 
jurisdiction of the FDA, in order to obtain permission for them to 
be marketed in the Republic of Belarus. Upon submission of 
information as listed in the Annexes, the Belarusian party intends 
not to require, as a condition of registration or importation, the 
conduct of any additional clinical or analytical review or testing, 
or any other medical, scientific, quality, or other related 
requirements. Registration should take no more than 60 days after 
the submission to the appropriate Belarusian party of all of the 
information required in the Annexes and payment of any fee(s) 
required by Belarus.
    Upon submission of a request for registration of vaccines and 
sera, the Ministry of Health of the Republic of Belarus may require 
additional documentation which will meet the requirements of the 
Republic of Belarus. In cases when additional documentation is 
necessary, the Belarusian party should notify the firm seeking 
registration within the 60 day period.
    5. Upon request of the Belarusian party, the FDA should provide 
access to information on the compliance status of drugs and 
biological products and manufacturers that are eligible for 
Belarusian registration under this Memorandum, to the extent the 
information is permitted by United States laws. The FDA should also 
respond to inquiries from the Belarusian party about information 
submitted in accordance with the Annexes with respect to such 
matters as the marketing status of any drug or biological product. 
The parties intend to share information about all drugs and 
biological products that present a significant risk to users.
    6. Upon request of the FDA, the Belarusian party will consider 
confidential any information provided to it by the FDA if it is not 
public information. Similarly, at the request of the Belarusian 
party, the FDA will respect the confidentiality of information 
provided by the Belarusian party to the FDA, to the extent permitted 
by law.
    7. Under this Memorandum of Understanding, subject to 
availability of resources, the parties plan to share knowledge and 
provide assistance and information to one another when necessary.
    8. The FDA should provide the Belarusian party with up-to-date 
copies of laws, regulations, provisions, and procedures used to 
ensure the level of quality of drugs and biological products, 
necessary for public health. The Belarusian party should provide the 
FDA with up-to-date copies of the laws, regulations, provisions, and 
procedures for registration of a given product imported into the 
Republic of Belarus from other countries and, in particular, from 
the United States. The Annexes to this Memorandum of Understanding 
should contain the sole procedure and list of requirements 
applicable to those products manufactured and marketed in the United 
States under the jurisdiction of the FDA.
    9. The parties should consult periodically, subject to the 
availability of funds, in order to promote cooperation and to 
facilitate implementation of this Memorandum of Understanding. As 
the need arises, the parties should develop and agree on a specific 
plan of cooperation.
    10. Subject to the availability of funds, the parties may 
establish a coordinating committee and one or more technical 
committees, including representatives of each party with knowledge 
in regulation of drugs and biological products, in order to 
facilitate implementation of this Memorandum of Understanding.

IV

    The following offices are designated as liaison offices for the 
parties:
A. For the FDA:
    Director
    (currently Bradford W. Williams)
    Division of Drug Labeling and Nonprescription Drug Compliance
    Office of Compliance
    Center for Drug Evaluation and Research
    Food and Drug Administration
    7520 Standish Place
    Rockville, Maryland 20855
    USA
B. For the Ministry of Health:
    Director of the Administration
    of Pharmacy, Medical Equipment, and Regulations
    Ministry of Health
    39 Myasnikov Street
    220097 Minsk
    Republic of Belarus
    Activities under this Memorandum of Understanding will begin on 
the last date of signature by all parties and will last for a period 
of three years. Activities under this Memorandum of Understanding 
may be extended or amended by mutual written consent. They may be 
terminated by any party by a sixty day advance written notice to the 
other parties done at Minsk, Belarus, in duplicate, in the English 
and Russian languages, this 27th day of March, 1996.

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

Mary Pendergast
Deputy Commissioner/
Senior Advisor to the Commissioner

For the Ministry of Health of the Republic of Belarus:

Inessa M. Drobishevkaia
Minister

Annex I

Application Procedures and Information Which the United States Firm 
Must Provide to Belarusian Authorities for Registration and/or Re-
registration in the Republic of Belarus of Drugs and Biological 
Products Manufactured and Marketed in the United States Under the 
Jurisdiction of the Food and Drug Administration (FDA)

    1. The manufacturing firm or their authorized representative 
shall submit one (1) English language and three (3) Russian language 
copies of an application which includes the following information 
to:
          Chief of the Pharmacy Department,
          Department for Pharmacy, Medical
          Equipment and Regulations
          Ministry of Health
          39 Myasnikov Street
          220097 Minsk
          Republic of Belarus
    2. Information on the manufacturing firm and/or their authorized 
representative including:
    a. Name of registering firm

[[Page 67564]]

    b. Name of manufacturing firm, if applicable (if representing 
another firm, a notarized letter authorizing the registering firm to 
register the products in Belarus)
    c. Address, telephone and facsimile numbers of registering and/
or manufacturing firm
    d. Name, title and signature of the authorized responsible 
representative(s)
    e. Certification that the drugs or biological products are 
manufactured in the United States.
    3. The FDA Letter of Approval, or, For products subject to an 
FDA Over-the-Counter (OTC) monograph, copies of the relevant 
sections of the Final Monograph or Tentative Final Monograph with a 
certification by the manufacturing firm and/or its authorized 
representative that the product conforms in all respects to the 
Final Monograph or Tentative Final Monograph.
    4. The FDA approved product package insert (information and 
instruction sheet), labels and labeling. The information provided 
must include the following:
    a. Name: trade, generic, and chemical
    b. Description: chemical and pharmacological group
    c. Clinical pharmacology/mechanism of action
    d. Indications and instructions for usage
    e. Contraindications
    f. Observations
    g. Precautionary measures
    h. Adverse reactions and toxicity data
    i. Information on overdose
    j. Dosage and methods of administration
    k. How medical product is supplied, including dosages and 
product strength
    l. Information on storage conditions and expiration.
    m. Other information contained in the insert.
    5. For the registration of prescription drugs (New Molecular 
Entities) manufactured in the United States and covered by an 
approved New Drug Application:
    a. 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:
    i. Pharmacological report (specifications) supporting all 
indications for usage as stated in the instructions, including 
summary of the pivotal clinical trials(s)
    ii. Toxicology report (acute, subacute, subchronic, and chronic 
toxicology)
    iii. Specific activity report related to the following: side 
effects, birth defects, allergies, skin irritations
    b. 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.
    c. A short summary of information about side effects of the 
pharmaceutical and any adverse experiences with the pharmaceutical 
learned since FDA approval.
    6. For the registration of generic drug products manufactured in 
the United States under the jurisdiction of the FDA:
    a. A summary bioequivalence study and results.
    7. Requirements for the registration of pharmaceutical 
substances manufactured and marketed in the United States:
    a. Certificate of Analysis for the substance from the 
manufacturing company (original copy or notarized copy).
    b. Information on the product(s) which will be manufactured in 
the Belarus using the substance.
    8. Methods of analysis and release specifications. Guidelines on 
documentation required are contained in Annex II.
    9. The manufacturing firm and/or its authorized responsible 
representative shall sign and submit a statement that the firm meets 
the current Good Manufacturing Practice (GMP) requirements.
    10. The manufacturing firm and/or its authorized representative 
shall provide a copy of the most recent FD-483, FDA Notice of 
Inspection Observations, that is relevant to the drug or biological 
product for which registration is sought.
    11. The manufacturing firm and/or its authorized responsible 
representative shall sign and submit a statement that all 
information submitted is truthful, accurate, and complete.
    12. In case of any change of information provided in the 
original application, including any FDA-approved changes in the 
package insert, labels or labeling, the manufacturing firm and/or 
its authorized representative shall provide notification of these 
changes within 30 days.
    13. The manufacturing firm and/or its authorized representative 
shall provide samples of the product in the packaged form in which 
the product is offered for registration.
    14. For re-registration of pharmaceutical or biological 
preparations manufactured and marketed in the United States:
    a. Copy of the original registration certificate issued by the 
Ministry of Public Health
    b. Complete information on changes in the composition or 
manufacturing process since the original registration
    c. Summary of information concerning side effects, adverse 
effects and complaints received by the firm during the previous 5 
years.

Annex II

Addendum 1

    Supplemental Guidelines for Submission of Methods of Analysis 
and Release Specifications in Applications for Synthetic Chemical 
Compounds (substances) for Registration in the Republic of Belarus
     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 Guidelines for the Submission of Methods for 
Analysis and Release Specifications in Applications for Liquid 
Injection Dosage Form Products for Registration in the Republic of 
Belarus
     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 Republic of Belarus
     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 (include 
weight tested)
    15. Heavy metals

[[Page 67565]]

    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 Guidelines for the Submission of Methods for 
Analysis and Release Specifications in Applications for Liquid 
Ophthalmic Dosage Form Products for Registration in the Republic of 
Belarus
     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 Guidelines 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 Republic of Belarus
     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 Guidelines for the Submission of Methods for 
Analysis and Release Specifications in Applications for Aerosol 
Dosage Forms for Registration in the Republic of Belarus
     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)

Annex II

Addendum 7

    Supplemental Guidelines for the Submission of Methods for 
Analysis and Release Specifications in Applications for Tablets and 
Dragee Dosage Form Products for Registration in the Republic of 
Belarus
     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 no. 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 Guidelines for the Submission of Methods for 
Analysis and Release Specifications in Applications for Solid Oral 
Capsule Dosage Form Products for Registration in the Republic of 
Belarus
     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/or
    5. Dissolution test, or release rate test
    6. Uniformity of dosage units test/content uniformity
    7. Solubility test
    8. Assay
    9. Microbiology purity test
    10. Impurity(ies) test(s) (Chromatographic Profile)

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    Requirements 6 and 7 apply to capsules in which proportion of 
active ingredient per one capsule amounts to 50 mg. or less.

Annex II

Addendum 9

    Supplemental Guidelines for the Submission of Methods for 
Analysis and Release Specifications in Applications for Suppository 
Products for Registration in the Republic of Belarus
     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 Guidelines for the Submission of Methods for 
Analysis and Release Specifications in Applications for Topical 
Solid Products for External Use for Registration in the Republic of 
Belarus
     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 Guidelines for the Submission of Methods for 
Analysis and Release Specifications in Applications for Tincture and 
Extract products for Registration in the Republic of Belarus
     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 Memorandum 
of Understanding.
[FR Doc. 96-32424 Filed 12-20-96; 8:45 am]
BILLING CODE 4160-01-F