Medical website August 3
I. background of revision of the code
In 2003, promulgated by the state food and drug administration "pharmaceutical non-clinical research and the quality control standard" (the original bureau no. 2), to regulate the industry, to promote drug research and development, to ensure drug quality has played a positive role in promoting.
Along with the continuous increase of drug non-clinical safety evaluation and research ability and the evaluation of the rapid growth of the number, as well as the pharmaceutical non-clinical research and the new concept in the field of production and application of new technology, need for pharmaceutical non-clinical research and the quality control standard for content adjustment and refinement, to meet the needs of the industry development and regulatory work.
Drugs in order to further implement the "state council on reform of medical equipment review system of examination and approval opinions" (guo fa [2015] 44), meet the needs of the development of drug non-clinical safety evaluation and research, refer to the international practice, administration organization revised "pharmaceutical non-clinical research and the quality control standard" (hereinafter referred to as "specifications").
The scope of application of the code
The specification applies to the study of drug non-clinical safety evaluation for the application of drug registration. The relevant activities of drug non-clinical safety evaluation study should abide by this specification. Drug metabolism, biological sample analysis and other pre-clinical research activities for the purpose of registration are carried out in reference to the code.
Iii. Consultation on the regulation
On August 17, 2016, the code issued a public consultation to the public and received a total of 178 comments from the parties. The comments were revised by the general administration.
In the process of modification, a reasonable suggestion was adopted, and six items were mainly summarized.
(I) further complements and clarifying the term definitions involved in multi-site studies;
(2) for the audit trails involved in computerized system, the definition and requirements of clear terms such as electronic data are defined and required;
(3) to increase the term definition and detailed retention requirements for subjects and controls;
(4) to define and specify specific requirements for the supplementary terms of the pathologic peer review;
(5) further clarification of the archives management and custody period;
(6) the importance of quality assurance shall be further strengthened, and the relevant description of quality assurance shall be provided.
There are three Suggestions for an unadopted recommendation:
(1) it is recommended that the content of the original "experimental scheme shall be approved by the head of the institution". It is in the responsibility of the project leader to approve the test plan, which is conducive to the realization of the rights and responsibilities. The opinion was not accepted.
(2) it is recommended to delete and ensure that the research institutions regularly participate in the necessary testing laboratory capacity verification and comparison activities. Laboratory proficiency testing and comparison activity is the guarantee drug non-clinical safety evaluation institutions, effective way to detect the data reliability shall, according to research needs, to participate in the necessary ability verification and comparison. The opinion was not accepted.
(iii) it is recommended to delete the principal chapters and contents. Clients as the sponsor of the research work and the results of the declaration, the declaration for registration of research materials, the right holder of the corresponding responsibility, in the relevant laws and regulations, the European and American countries for pharmaceutical non-clinical research and the clients have clear responsibility requirements. The opinion was not accepted.
Iv. Contents of the revised regulations
(a) "specification" increased from the original article 45 to 50, delete the original "specification" in "the supervision and inspection" section, the new "terms and their definitions", "experimental system", "quality assurance" and "the client" section.
(2) to cancel the work style and professional ethics requirements of the staff in the original code; The restrictions on the background of the institution's responsible person and education are eliminated.
(iii) main contents of adjustment:
1. The original "specification" for quality assurance director duty requirement is adjusted for quality assurance requirements the responsibility of the personnel and the quality assurance, clear quality assurance department responsible for checking the implementation of this specification, to ensure the operation and management of research in accordance with the specification requirements.
2. The data files to the shelf life of the original "specification" of "drugs listed at least five years after the adjustment for" used to register to declare materials, its archives shelf life shall be at least five years after the drugs listed; (if the study of termination is not used in the study of registered declaration materials), the archival retention period shall be at least five years after the conclusion of the report. Other information that does not belong to the scope of the study should be kept for at least a decade after it has been generated.
3. The archival time of the data files shall be adjusted to "after the study of the code" to "be archived in time after the study is carried out or after the research is completed, and the maximum shall not exceed two weeks".
(iv) main contents of the increase:
1. The study on non-clinical safety evaluation of drugs should ensure that the code of conduct is accurate, accurate and complete.
2. Increase the non-clinical research and the quality control standard, place study, body or the main researchers, standard operating procedures and main schedule, test plan, test plan changes, deviations, solvent, research start date, completion date, computerized systems, authentication, electronic data, electronic signature, audit trails, term definition of peer review.
3. The staff should be responsible for the quality of raw data and take necessary protective measures according to the needs of the job.
4. Increased the head of the institution (including the head of the site of research in multiple places) to ensure that the operational management of the research institutions met the requirements of this specification; Ensure that the research institutions participate in the necessary testing laboratory capacity verification and comparison activities.
5. Increased the responsibility of the project leader for the implementation and summary report of the study, including the approval of test programmes and summary reports in the form of names and dates; In multi-site studies, it is important to ensure that the main investigator's part of the test work conforms to the requirements of this specification.
6. Increased the test duration exceeds surrounding, each batch of subjects and reference substance all ought to return enough samples, for the need of back analysis, and saved as files to be archived after completion of the study.
7. Increasing the use of experimental animals should be concerned with animal welfare and following the principle of "reduction, substitution and optimization", which should be approved by the animal ethics committee before implementation.
8. Increase the experimental animal experiment system other than the source, quantity (volume), quality attributes, such as receiving date shall be detailed records, and kept under appropriate environmental conditions and operation; The applicability assessment should be carried out before use, and the applicability of the quality problems should be properly handled and reassessed.
9. When the study is cancelled or terminated, the change of test plan shall indicate the reason for the cancellation or termination and the method of termination.
10. Increase the generation and modification of electronic data to meet relevant requirements.
11. The relevant requirements of the peer review plan, management, records and reports have been added to the work of the pathologist.
12. Increased demand for computerized system: used for data acquisition, transmission, storage, processing and archiving of computerized systems (or contains a computer system of the equipment) shall be verified. Electronic data generated by computerized systems should have a complete audit trail and electronic signature. The head of the agency shall ensure that the computerized system is applicable to its use and shall be verified, used and maintained in accordance with the requirements of this specification. The project leader should ensure that the computerized system is validated or verified and is in a state of application.
13. Increased research in the process of test plan and the divergence of standard operating procedures, to participate in research personnel should be recorded in a timely manner and report to project director, in the case of a place to study should also report to the principal investigator is responsible for the relevant test. The project leader or principal investigator should assess the impact of the reliability of the data and take corrective action if necessary.
14. Added quality assurance section to ensure the independence and implementation of quality assurance work; The quality assurance department shall issue a quality assurance statement to the audit project; The quality assurance inspection is divided into three types: research-based, facility based and process-based.
15. When the study has been cancelled or terminated, the project manager shall keep the research data that has been generated as a research archive for archiving.
16. Increase the archives institutions out of business or expiration of this case file shall be transferred to the client's file facilities or to the specified file facilities in custody, until finally the duration of the file.
17. The entrusting party, as the initiator of the research work and the declarer of the study results, is responsible for the research data used to declare the registration and shall bear the corresponding responsibilities. |
