Draft 07 Circular Guiding Drug Bioequivalence 7/11/2016
| MINISTRY OF HEALTH
|THE SOCIALIST REPUBLIC OF VIETNAM Independence – Freedom – Happiness|
|Hanoi, [date] 2016|
Guiding drug bioequivalence
Pursuant to Pharma Law No. 105/2016/QH13 dated 6th April 2016;
Pursuant to Decree 63/2012/NĐ-CP dated 31st August 2012 by the Government stipulating for functions, missions, and authority and organizational structure of Ministry of Health;
Pursuant to Decree…. on implementation of Pharma Law 105/2016/QH13;
At the request of the Director General of Administration for Science, Technology and Training;
The Minister of Health hereby promulgates this Circular providing for conditions, authority, and procedures to register for drug bioequivalence research activities in Vietnam.
Article 1. Scope
This Circular provides for conditions, authority, dossier and procedures to register for research activity of drug bioequivalence by facilities conducting drug bioequivalence research in Vietnam.
Article 2. Definitions
A facility that conducts drug’s bioequivalence (“Research Facility”) is an organization with adequate conditions that has been approved by competent authorities to conduct research to assess drug equivalence on human beings as the subject of research in Vietnam.
Bioavailability is a feature the presents the speed and magnitude of absorption of a pharmaceutical substance or a group of substances that have effects on general circulation and are available at the site of intervention, or presents the magnitude and speed of a pharmaceutical substance or a group of substances with effects that are released from a dosage form and become available in general circulation.
Bioequivalence: two drugs are considered bioequivalent if they are drugs with equivalent dosage or if they are dosage alternatives, and have equivalent bioavailability when used at the same dose in the same trial conditions, leading to the fact that their therapeutic effectiveness is basically considered equivalent.
Article 3. General principles in conducting research on drug bioequivalence
1. Any research activity to assess drug bioequivalence must be conducted in conditions compliant with good clinical practice and good laboratory practice principles, and can only be conducted once the research protocol has been approved by competent authorities.
2. Any facility that conducts research activity to assess drug bioequivalence must be qualified for good clinical practice and good laboratory practice, and must be allowed by competent authorities to conduct biomedical research on human beings.
3. Any drug for which research is conducted must be manufactured, managed, and stored in line with good manufacture practice (GMP) and good storage practice (GSP) guidelines, and can only be used for approved research.
4. Any research facility is responsible to manage all research activity to assess drug bioequivalence that it conducts.
OPERATION CONDITIONS FOR RESEARCH FACILITIES
Article 4. General conditions for any facility that registers any research activity to assess drug bioequivalence in Vietnam
1. Such facility must have a mandate of scientific research and must be organized as an independent center or a partnership between a facility that conducts clinical research and a facility that conducts analysis to determine drugs’ concentration in biological fluids.
2. Any facility that conducts clinical trial in assessing drug bioequivalence must have a mandate of medical examination and treatment and must meet criteria for clinical trial service providers set in Annex 1 hereof.
3. Any facility that conducts biological fluid analysis must be compliant with good laboratory practice criteria, with sample scope certified to meet the conditions to conduct tests to determine drug samples in biological fluid.
4. Such facility must have an ethics committee in biomedical research at grass-root levels (IRBs), which operates under the provisions of Decision No. 111/QĐ-BYT dated 11th January 2012 by Minister of Health.
5. In case a research facility is organized following a partnership model, the facility must enter a research contract with a facility that conducts clinical research that meets all requirements specified under Article 7 hereof.
Article 5. Manpower conditions for research facilities
1. A research facility must have staff dedicated to the following positions: technical lead(s), researcher(s), and quality assurance controller(s).
2. A quality assurance controller must work independently and must not take other positions simultaneously, and shall report directly to the head of the research facility.
3. A filing system of CVs and training profiles of all staff members working for a research facility must be established and maintained.
4. Lead researchers and researchers must have educational background of bachelor degree or higher with appropriate technical expertise and capability to conduct approved research.
6. Implementers of clinical research must have practicing certificate for medical examination and treatment and training certificate on GCP accredited by Ministry of Health.
7. Researchers conducting biological fluid analysis must have relevant analytical expertise and training in GLP, and shall be responsible for the accuracy and reliability of analytical data during trial research.
Article 6. Infrastructural conditions for research facilities
Research facilities must arrange for the following technical areas and equipment to conduct research:
1. A clinical research site must at least have the following rooms and areas:
a) Room for registration and screening of volunteers;
b) Room for relaxation and entertainment for volunteers and supporting area.
c) Room for dosage division and drug use indication and sample collection;
d) Room for sample processing and storage;
e) Area for storage and re-packaging of drugs and for distribution of drugs and materials.
f) Room for standard food preparation.
g) Dining room for volunteers.
h) Area for storage and management of files and documents.
2. A site to conduct biological fluid analysis must meet the requirement of “Good laboratory practice” specified under Decision 03/QĐHN-BYT dated 04/10/2013 by Minister of Health.
3. Equipment conditions of research facilities”
a) Equipment for clinical research must meet the requirements set for drug clinical trial service providers specified under Annex 1 hereof.
b) Equipment for analytical phase must meet the requirements of GLP specified under Decision 03/QĐHN-BYT dated 04/10/2013 by Minister of Health.
c) Computers and software to store and keep research data confidential.
Article 7. Requirements for research partnership contracts
Research partnership contracts entered between biological fluid research facilities and medical examination and treatment facilities to conduct clinical research must comply with applicable legal provisions and must reflect explicitly the following:
1. The final and ultimate responsibilities of the parties in ensuring maximum safety for research subjects and when an adverse event happens to research participants.
2. Responsibilities of the clinical research facility in ensuring safety and handling adverse events against research participants during clinical research stages.
3. Location(s) where clinical research shall be conducted, with specified addresses.
4. Contracts must be valid for at least two (02) years from submission of research activity registration dossiers by research facilities.
REGISTRATION AUTHORITY, DOSSIERS, AND PROCEDURES FOR RESEARCH FACILITIES
Article 8. Authority to receive registration for research activity to assess drug bioequivalence
Before conducting any research activity to assess drug bioequivalence, a research facility is responsible to fulfill registration or notification by forms specified under Article 10 hereof to Administration of Science, Technology and Training under Ministry of Health.
Article 9. Types of registration and notification of research activities to assess drug bioequivalence in Vietnam.
1. Registration for research activity to assess drug bioequivalence.
2. Notification of changes/additions to legal representatives, technical leads, names and address or administrative contact details of research facilities.
Article 10. Registration dossiers
Any research facility who registers for research activity to assess drug bioequivalence shall submit a set of dossiers including:
1. Application form for research activity to assess drug bioequivalence using Form 01 attached herewith.
2. A copy of one of the following: Establishment decision, Practice License, Investment License, Certificate of business registration or equivalent.
3. A copy of practice license of the medical examination and treatment facility.
4. A copy of practice license of the biological fluid facility.
5. A copy of GLP certificate of the biological fluid facility.
6. A copy of certificate for Clinical Trial Service Provider Qualification for the clinical research facility issued by a competent authority.
7. A copy of decision to establish ethics committee in biomedical research at grass-root level (IRB) for the research facility.
8. A partnership contract with the medical examination and treatment facility to conduct clinical research (in case of partnership arrangement).
9. Manpower profile of the research facility:
a) Manpower list using Form 02 attached herewith.
b) A copy of university degree or above in the health sector and other relevant certificates/diplomas of personnel involved in conducting clinical research and biological fluid analysis
c) A copy of medical examination and treatment practice licenses of personnel conducting clinical research.
d) A copy of GCP certificates or accreditations for personnel conducting clinical research issued by Ministry of Health or Ministry of Health’s accredited organizations as stipulated under Article 11 of Circular 03/TT-BYT dated 02/02/2012 by Minister of Health.
11. Infrastructure profile of the research facility: List of infrastructure/facilities available using Form 03 attached herewith.
12. Equipment profile of the research facility: List of equipment of the research facility using Form 04 attached herewith.
Article 11. Notification of changes/ additions to legal representatives, technical leads, names and address or administrative contact details of research facilities
Research facilities shall send notification documents including:
1. Notification of changes/ additions using Form 05 attached herewith, together with documents to prove such changes.
2. A certified copy of degrees and certificates relating to professional areas of expertise of the legal representatives or technical leads in case of change of legal representatives and technical leads.
Article 12. General conditions regarding language, format and legal validity of dossiers
1. Language used in dossiers: Registration dossiers by research facilities shall be in Vietnamese. Any foreign technical documents must be translated into Vietnamese.
2. Format of dossiers: Registration dossiers for research activity to assess drug bioavailability and bioequivalence must be prepared in A4 paper size and firmly bound, with a table of content and document arrangement in order of such table of content, with clear and numbered separation and indication between sections for easy reference.
3. Legal validity of dossiers: Application form and content of registration dossiers must be signed and stamped by legal representatives of the research facilities as legally stipulated. Legal documents of foreign origins must be certified by competent authorities for signature and consular legalization as legally stipulated.
Article 13. Procedures to register for research activity to assess drug bioequivalence.
1. Procedures to register for research activity to assess drug bioequivalence:
a) Research facilities shall send 01 original set of registration directly to Ministry of Health.
b) MoH’s Administration for Science, Technology and Training is the focal point to receive registration dossiers from research facilities, with receipts using Form 06 attached herewith and shall provide guidance on any additions required for incomplete registration dossiers.
c) Within 30 working days after receiving complete registration dossiers, Administration of Science, Technology and Training shall consider and issue a document to accept research activity to assess drug bioequivalence using Form 07 attached herewith. In case a registration dossier is refused, the Administration for Science, Technology and Training must notify in writing using Form 08 attached herewith, specifying reasons for such refusal.
2. Sequences for registration for changes/ additions:
a) Research facilities send 01 set of notification documents directly to Ministry of Health within 07 working days when there is a change/ addition and shall be responsible for such information.
b) Administration of Science, Technology and Training shall serve as the focal point to receive notification dossiers from research facilities.
Article 14. Organization and activities of appraisal team appraising registration dossiers for research activity to assess drug bioequivalence in Vietnam
Article 15. Reviewing research facilities’ operation
1. Ministry of Health shall organize periodic or reviews of activities of research facilities that conduct assessment of drug bioequivalence in Vietnam.
2. Sequence for reviewing:
a) Ministry of Health shall send notification 10 working days in advance before conduct any on-site review of any facility that has registered for research activity to assess drug bioequivalence in Vietnam, using Form 10 attached herewith.
b) Facilities that have registered for research activity to assess drug bioequivalence in Vietnam are responsible to prepare for human resources and working topics per Ministry of Health’s notification.
c) Within 20 working days after conducting a review, Ministry of Health shall send review results in writing to the facility in question that has registered for research activity to assess drug bioequivalence in Vietnam.
3. Research facilities are responsible to abide by review conclusion by Ministry of Health.
Article 16. Validity
This Circular is valid from [date….] 2017.
Article 17. Transition
Organizations that have been conducting research activities to assess bioequivalence before the Circular takes effect must complete registration procedures as specified by this Circular by [date…] 2017.
Article 18. Responsibility for execution
1. Ministry of Health assigns Administration of Science, Technology and Training to serve as the focal point and coordinate with relevant departments to execute this Circular.
2. Heads of relevant agencies, organizations and units are responsible to communicate the Circular to stakeholders so that they become aware and execute.
During execution, should there be any bottlenecks, agencies/organization/individuals are requested to report in a timely manner to Administration of Science, Technology and Training for consideration and resolution./.
Sent to: – Prime Minister (for reporting);
– Deputy Prime Ministers (for reporting); – Ministries, ministry-level agencies, and agencies under direct management of the Government;
– People’s Committees in provinces and city under direct management of the central government;
– Agency of Examination of Legal Normative Documents (Ministry of Justice);
– Minister, Vice Ministers;
– Departments, Administrations, General Directorate, Ministry Inspectors, and Ministry Office;
– Units directly under MoH;
– MoH’s gazettes and web page; – Archived: VT, PC, K2ĐT (5 copies).
Draft 07 Circular Guiding Drug Bioequivalence