OBJECTIVETo study the pharmacokinetics and bioequivalence of asparaginase loaded in hyaluronic acid-graft-poly(ethylene glycol)/ sulfobutylether-β-cyclodextrin nanocapsules (AHSP) in SD rats.

METHODSThe morphology of AHSP was observed under the transmission electron microscope and the particle size and zeta potential were measured. AHSP and free asparaginase were intravenously injected in rats, and the plasma asparaginase activity was measured at different time points after the injections. The pharmacokinetic parameters were calculated using the software DAS 2.1.1 to assess the bioequivalence of AHSP and free asparaginase.

RESULTSAHSP had an average particle size of 413.80∓10.97 nm with a zeta potential of -20.37∓2.38 mV. The AUC(0-48 h) of AHSP and free asparaginase was 137.34∓1.82 U/mL and 46.38 ∓1.98 U/mL, and their AUC(0-∞) was 164.66∓6.88 U/mL and 51.44∓3.01 U/mL with half-lives of 4.62∓0.60 h and 1.86∓0.38 h, respectively. Compared with free AN, AHSP exhibited increased AUC(0-48 h), AUC(0-∞), and half-life by 2.24, 2.55 and 2.32 folds, respectively. The 90% confidential intervals of AUC(0-48 h), AUC(0-∞) and Cmax of the tested formulation were 75.0%-76.5%, 74.3%-76.1%, and 95.1%-96.7%, respectively.

CONCLUSIONAHSP can improve the bioavailability and extend the biological half-life of asparaginase in rats, and AHSP and free asparaginase are not bioequivalent.

Animals ; Area Under Curve ; Asparaginase ; pharmacokinetics ; Biological Availability ; Half-Life ; Injections, Intravenous ; Nanocapsules ; Rats ; Rats, Sprague-Dawley ; Therapeutic Equivalency

OBJECTIVE： To provide references for improving the standard operating procedures of drug management in clinical trials and drug management in clinical trials. METHODS： According to Good Clinical Practice （GCP）， Data On-site Verification Points of Drugs Clinical Trial， Qualification Examination Rules of Drug Clinical Trial Institution， based on the quality control project carried out in our hospital since July 2016， the matters needing attention in the non-standard operation and key process of drug management in clinical trial were summarized， and the improvement measures were discussed. RESULTS & CONCLUSIONS： Non-standard drug management is a high-incidence link of non-standard operation in the trial process. Among them， the acceptance， distribution and use of drugs are the three links with the highest incidence of non-standard operation of drug management in the trial process. Therefore， when formulating the relevant management system， each institution should pay attention to it according to its own situation； such as， when accepting drugs in clinical trials， attention should be paid to checking the intact degree of drug packaging； drugs transported in cold chain should also be checked for temperature records and rejected in case of over-temperature； the copies of the waybill should be kept in file with the original to avoid fading of the thermosensitive paper； whether the relevant characteristics of the control drugs and placebos meet the requirements. Institutions can standardize the key links of drug management in the trial process， the time of project establishment， project start-up， quality control and supervision， formulate and constantly improve the relevant drug management system and standard operating procedures （SOP）. For example， when starting a project， attention should be paid to the participation of drug administrators in the training and signature of start-up meeting， whether the design of the form is complete， standardized and operable. It is necessary for clinical trial institutions to pay attention to the standardization and precision of drug management and the key links in clinical trials.

OBJECTIVE To learn the common proto col deviation （PD）in the process of drug clinical trials and discuss the methods and precautions for preventing and reducing PD so as to provide reference for the standardization of drug clinical trials. METHODS According to Good Clinical Practice ，Notice on Issuing Guidelines for Planning and Reporting of Data Management and Statistical Analysis of Drug Clinical Trials ，Guidelines for Ethical Review of Drug Clinical Trials ，ICH E 3，ICH E 6（R2）and other regulations ，the PD reported in the relevant projects managed by the author from March 2017 to February 2022，as well as the PD found in the submission materials and project quality control ，were sorted out and statistically analyzed. RESULTS & CONCLUSIONS A total of 39 drug clinical trials were included ，and 212 subjects were selected. In all projects ，258 PDs were reported，including 28 major PD （accounting for 10.85％）and 230 ordinary PD （accounting for 89.15％）. The report of PD mainly included missed inspections/tests （93 reports，accounting for 36.05％），lack of visits （36 reports，accounting for 13.95％）， inspection/testing out-of-window （29 reports，accounting for 11.24％），dosage and usage of test drugs （28 reports，accounting for 10.85％），drug over-temperature/missing temperature （21 reports，accounting for 8.14％），etc. Avoiding and reducing the occurrence of PD requires the efforts of multiple parties ：the sponsor designs a reasonable protocol with appropriate interview rate and window period after listening to the opinions of multiple parties ；the investigators and clinical research coordinator should strengthen their own learning and training ，and be familiar with the protocol ，Good Clinical Practice and corresponding regulations；the compliance education of the subjects should be strengthened ；the institutional offices and ethics committees should conduct multi-angle and whole-process supervision and management when a drug clinical trial is approved ，in progress ，and jsyj- concluded，to ensure the safety rights and interests of the zdcxX0079） subjects and the quality of clinical trials. On this basis ，all parties should communicate effectively and timely ，report PD in time ，and conduct special studies on major PD that have com occurred and key links that are prone to PD.

OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.

OBJECTIVE To investigate the current situation of clinical trial institutions in Chongqing after the recording system of clinical trial institutions, and to put forward suggestions. METHODS A total of 34 clinical trial institutions in Chongqing were selected as the research objects. The research contents mainly included the basic situation of the institutions, staffing, hardware and software construction, project operation and work difficulties, etc. Combined with the research results, suggestions were put forward for the difficulties of the new and old institutions in the operation of clinical trial institutions. RESULTS A total of 29 questionnaires were collected and 29 were valid. The release of clinical trial resources in Chongqing were not sufficient and uniform, there were problems such as insufficient incentive policies, lack of information platform construction, and the number and professional degrees of practitioners need to be improved. The new institutions had certain advantages in project load, office space and willingness to undertake, but it was restricted by principle investigator qualification, project experience and institutional reputation. CONCLUSION It is suggested to clarify the incentive mechanism, enhance the enthusiasm of clinical trials and establish a standardized training mechanism for clinical trial professionals. Make full use of the information platform to improve the efficiency of clinical trials, build a regional information platform to share information and resources, and accelerate the development of regional clinical trials.