Standard on Bioequivalence Study Management

Ministry of Food and Drug Safety Notice No. 2017-30

Partially amended and Enforced on April 28, 2017

CHAPTER 1. GENERAL PROVISIONS

Article 1 (Purpose) The purpose of this Notice is to obtain accurate and reliable data and results by establishing
the criteria for the approval procedure of bioequivalence study, the operation and management of
bioequivalence study institutes and the proper performance of bioequivalence studies according to Article
34 and 34-2 of the Pharmaceutical Affairs Act, Articles 25, 31, and 35 of the Regulation on Safety of
Medicinal Products, etc. and Article 57 of Act on the Control of Narcotics, etc.

Article 2 (Definition) The definition of the terms used in this Notice shall be as follows:
1. The term “Study institute” means the medical or analysis institutes designated by the Minister of Ministry
of Food and Drug Safety (MFDS) which conducts bioequivalence study (“hereinafter referred to as
bioequivalence study”) according to Article 35 of the Regulation on Safety of Medicinal Products, etc.
2. The term “Sponsor” means an individual, company, study institute, or organization responsible for the
planning, management, and financing of a bioequivalence study. <Revision of the previous sentence>
3. The term “Principal investigator” means a person who takes the responsibility for bioequivalence study
in a study institute. <Revision of the previous sentence>
4. The term “Subinvestigator” means a person who is in charge of the works related to bioequivalence study
or who determines necessary matters under the authority and supervision of the principal investigator.
5. Deleted
6. The term "Operating officer" means a person who is entrusted with some of the duties of the head of a
study institute according to Article 5 in an analysis institute (hereinafter referred to as "analysis institute")
among analysis institutes according to Article 35 (2) subparagraphs 1 and 3 of the Regulation on Safety
of Medicinal Products, etc.
7. Deleted
8. The term "Standard operating procedure (SOP)" means a document elaborating the relevant procedures
and performance methods for the purpose of consistent performance of a particular task in a standardized
manner.
9. The term "Reliability assurance work" means the audit of the study and facilities and other tasks
conducted by a person designated by the head of the study institute or the operating officer to verify the
reliability of test results in the analysis institute.
10. The term "Inspection" refers to the act of the Minister of MFDS to officially investigate all facilities,
documents, records, etc. in the field of study institute, sponsor or contract research organization, etc. in
 order to verify that bioequivalence studies have been conducted in accordance with the relevant
regulations.
11. The term “Study data" means all the documents, data, original records or the official copies of the
originals which record selection of subjects, blood and urine collection, evaluation of analysis method,
sample analysis, calculation, statistical process, and other actions, etc., as the data needed to reproduce
and to evaluate bioequivalence study, and they may include pictures, micro-films, microfiche copies,
magnetic tapes, computer-readable media, data recorded in automatic scanning device and other data
storage media.

CHAPTER 2. SPONSOR, ANALYSIS INSTITUTE, ETC.

Article 3 (Sponsor) (1) Deleted
(2) The sponsor shall enter into a contract with the head of the analysis institute in a document concerning the
study plan and responsibilities and rights in accordance with Article 25 of the Regulation on Safety of Medicinal
Products, etc.
(3) Deleted
(4) The sponsor shall inspect whether the progress of the bioequivalence study of the analysis institute has been
conducted in accordance with the SOP and the relevant regulations, and he/she shall document the results.
(5) Deleted

Article 4. Deleted

Article 5 (Responsibilities of Head of Analysis Institute) (1) Deleted

(2) Deleted
(3) Deleted
(4) The head of the analysis institute shall verify that a proper and technically sound SOP is prepared and
complied, approve the enactment, revision, modification, and abolition of all SOPs, and maintain the SOP files.
(5) The head of the analysis institute shall designate a person in charge of reliability assurance and verify that
reliability assurance work is carried out according to this Notice.
(6) The head of the analysis institute shall have the necessary laboratories, facilities and experts to conduct the
relevant bioequivalence study, and shall be prepared to conduct the relevant bioequivalence study properly,
including taking necessary measures in case of emergency.
(7) The head of the analysis institute shall actively cooperate when requested by the sponsor or the Minister of
MFDS to browse the SOP directly.
(8) The head of the analysis institute shall have the relevant principal investigator actively cooperated when
he/she is notified of the inspection pursuant to Article 15.
(9) Deleted
(10) The head of the analysis institute shall designate a person in charge of storage of records and data transferred
from the principal investigator and preserve them in accordance with Article 31 Subparagraph 10 of the
Regulation on Safety of Medicinal Products, etc. However, if there are other regulations concerning the storage
of records and data, the regulations shall be complied with.
(11) The head of the analysis institute shall provide education and training so that each subinvestigator can
clearly understand the duties which he/she is required to perform and comply with ethics and compliance and
shall maintain the relevant records.
(12) The head of the analysis institute may require the operating officer to perform the duties of paragraphs 4,
5, 7 and 8.

Article 6 Deleted

Article 7 Deleted

Article 8 Deletion

Article 9 (Person in Charge of Reliability assurance) (1) A person in charge of reliability assurance shall
maintain all the copies of study protocols and SOPs approved by the relevant analysis institute.
(2) A person in charge of reliability assurance shall verify that matters necessary compliance for Article 34 and
34-2 of the Pharmaceutical Affairs Act, Articles 25, 31 and 35 of the Regulation on Safety of Medicinal
Products, etc., and this Notice are included in the protocols and SOP, etc. and document this.
(3) A person in charge of reliability assurance shall conduct an examination to ensure that all tests are carried
out in accordance with this Notice, and on the basis of the result of the examination, he/she shall determine and
record whether subinvestigators comply with the protocol and SOP.
(4) A person in charge of reliability assurance shall inspect the results report to ensure that the methods,
procedures and observation results are accurately and completely described and that the reported results reflect
the study data accurately and completely.
(5) A person in charge of reliability assurance shall swiftly report the examination results to the head of the
analysis institute or the operating officer and the principal investigator in writing.
(6) A person in charge of reliability assurance shall prepare and write his/her signature on a reliability assurance
certificate. The reliability assurance certificate shall include the date of the examination performance, the details
of the examination, the date reported to the head of the analysis institute and the principal investigator and
should be attached to the results report.
(7) A person in charge of reliability assurance cannot participate in a study which he/she should certify.

Article 10 (Standard Operating Procedure) (1) Standard operating procedure shall be prepared including the
following matters in the analysis institute's works:
1. Deleted;
 2. Deleted;
3. Deleted;
4. Deleted;
5. Receipt, identification, handling and storage of sample for analysis;
6. Sample processing and analysis;
7. Device usage and management;
8. Repair, maintenance and management of the computer system;
9. Materials, reagents and solutions: Preparation of drugs and their identification: dispensing and
identifying;
10. Preservation, reporting, storage and retrieval of records;
11. Activities of a person in charge of reliability assurance;
12. Other necessary matters.
(2) The analysis institute shall ensure that SOP related to the performed activities is placed to be easily used.
(3) The analysis institute shall record any deviations from SOP in relation to the study, and the principal
investigator shall be well informed.
(4) When the analysis institute revises SOP, it shall record, maintain and preserve its contents and the date.

Article 11 (Principle Investigator and Subinvestigator) (1) Principal investigator and subinvestigator of the
analysis institute shall have the necessary education and training and sufficient experiences in order to properly
perform the bioequivalence study according to the bioequivalence study protocol approved by the Minister of
MFDS, and if requested by the sponsor, the IRB according to Section 2 of Annex 4. Good Clinical Practices of
the Regulation on Safety of Medicinal Products, etc. (Ordinance of the Prime Minister), or the Minister of
MFDS, they should verify this through recent resumes or other related documents.
(2) The duties and compliance matters of the principal investigators of the analysis institute are as follows:
1. Duties
A. Deleted;
B. Deleted;
C. Appointment, division of duties, technical guidance and supervision on subinvestigators;
D. Securing analyzers, major equipment, necessary supplies, reagents, etc. to be used;
E. Deleted;
F. Deleted;
G. Deleted
H. Record of study data;
I. Writing study report.
2. Compliance matters
 A. The principal investigator shall perform the study by complying with the protocol agreed with the
sponsor and approved by the IRB and the Minister of MFDS. However, if the study was performed
differently from the approved protocol, the details and valid reasons should be documented.
B. Deleted
C. Deleted
D. The principal investigator shall carry out the study properly in close cooperation with the sponsor
and the IRB, and after completion of the study, he/she shall prepare the bioequivalence study report
(this only applies to the work carried out in the analysis institute) which meet the provision of
Article 18 of the Standard on Pharmaceutical Equivalence Study (MFDS Notice) and submit it to
the sponsor.
E. The protocol and its amendments shall be forwarded to a person in charge of reliability assurance,
and communication shall be made effectively with the person in charge of reliability assurance
during the conduct of study where necessary.
F. Deleted
G. Deleted
(3) Deleted
(4) Deleted
(5) The subinvestigator of the analysis institute shall comply with (2) 2 A.

CHAPTER 3 Deleted

Article 12 Deleted

Article 13 Deleted

Article 14 Deleted

CHAPTER 4. INSPECTION OF RELIABILITY AND DATA STORAGE, ETC.

Article 15. (Inspection of Reliability for Evaluation Result) (1) The Minister of MFDS, if necessary, may
require the relevant officials and/or the experts designated by the Minister of MFDS to investigate all matters
related to the study result in order to verify the reliability on the bioequivalence study.
(2) The Minister of MFDS, if necessary, may require the relevant officials and/or the experts designated by the
Minister of MFDS to visit the study institute unexpectedly so that they can supervise the intermediate study
process, review and confirm whether the relevant bioequivalence study is carried out or documented in
accordance with the protocol, SOP, this Notice and the relevant regulations.
(3) The experts of Paragraphs (1) and (2) may avoid the inspection on their own if there are reasons why it is
difficult to expect a fair verification of reliability.

Article 16. (Storage of Data and Sample, etc.) (1) The sponsor shall preserve the data of subparagraph 3 of
the following subparagraphs, and the storage officer shall preserve the data of subparagraphs 3 to 7 of the
following subparagraphs according to subparagraph 10 of Article 31 of the Regulation on Safety of Medicinal
Products, etc.
1. Deleted
2. Deleted
3. The amount of test and reference drugs to reproduce bioequivalence study, which should have the same
lot numbers used in bioequivalence study. However, the analysis institute among study institutes is
excluded.
4. All inspection records carried out by the reliability assurance work. However, the medical institute
among study institutes is excluded.
5. Records of subinvestigators on qualification, training, experience, and task division. However, the
medical institute among study institutes is excluded.
6. Document and record of the use and management of devices. However, the medical institute among
study institutes is excluded.
7. Files for past records of all SOPs.
(2) Data stored in the data storage room may be indexed to facilitate storage and retrieval.
(3) The analysis institute must preserve the analysis sample until the date of product approval or notification
(the date of removal of the approval conditions if there are any approval conditions).

Article 17. (Noncompliance) (1) In the course of study, if the fact that the principal investigator of the analysis
institute did not comply with Articles 34 and 34-2 of the Pharmaceutical Affairs Act, Articles 25, 31 and 35 of
the Regulation on Safety of Pharmaceuticals, etc., and this Notice is discovered, the sponsor shall take proper
steps to correct this and prevent recurrence, and if significant and continuous noncompliance is found, he/she
shall stop the study and report it to the Minister of MFDS.

CHAPTER 5. SUPPLEMENTARY RULES

Article 18. (Other Matters) (1) Matters not specified in this Notice regarding the management of
bioequivalence study shall follow what the Annex 4. Good Clinical Practices of the Regulation on Safety of
Pharmaceuticals, etc. (Ordinance of the Prime Minister) and the Standard on Pharmaceutical Equivalence Study
stipulate.
(2) When bioequivalence study report is submitted for the product approval application (product notification)
(including amendment), this report should be published by the head of the study institute according to Article 3
of this Notice.

Article 19. (Review Period) According to Article 8 of the Framework Act on Administrative Regulations and
the Regulation on Issuance and Management of Instructions and Rules」(Presidential Instruction No. 248),
validity of regulations must be reviewed and actions of improvement must be taken every 3 years (by December
31 of every third year) starting January 1, 2014.

ADDENDUM <No. 2017-30, April 28, 2010>

This Notice shall be effective from April 29, 2017.