[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
