An Overview of Quality Management of Therapeutic Vaccines in Clinical Trials in China

Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.

Research on Construction of Pharmacovigilance System for Marketing Authorization Holders in China

Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the multinational pharmaceutical companies were analyzed based on the requirements of regulations and laws.Results and Conclusion There are some gaps between local and multinational pharmaceutical companies in the construction of pharmacovigilance system.We can learn from the experience of multinational pharmaceutical companies to improve the pharmacovigilance system,which includes building a sound pharmacovigilance organizational structure,establishing a series of operational system files and cultivating professional talents.MAHs of China should improve the structure of enterprise pharmacovigilance system.Besides,members of Drug Safety Committee should be department managers with higher position so that they can fulfil the responsibilities of risk assessment.If MAHs possess a large variety and quantity of products,a Drug Safety Committee should be established to ensure the timely discovery of risks.In addition,MAHs should pay attention to the implementation of related regulations and laws on pharmacovigilance and establish compliant,effective and operatable files combing with the actual operation of pharmacovigilance system.Finally,MAHs should introduce and train pharmacovigilance talents,and hire pharmacovigilance experts as consultants to solve the problem of talent shortage.

Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.

Study on good clinical practices among researchers in a tertiary healthcare institute in India

BACKGROUND Good clinical practice(GCP)is put in place to protect human participants in clinical trials as well as to ensure the quality of research.Non-adherence to these guidelines can produce research that may not meet the standards set by the scientific community.Therefore,it must be ensured that researchers are wellversed in the GCP.But not much is known about the knowledge and practices of the GCP in the medical colleges of North India.AIM To assess the knowledge and practices of researchers about GCP and analyze these with respect to the demographics of participants.METHODS This is a cross-sectional study.A self-structured questionnaire about GCP,after expert validations,was circulated among researchers,at a tertiary healthcare institute,All India Institute of Medical Sciences(AIIMS),Rishikesh.A total of 59 individuals,who were selected by universal sampling,participated in the study.All healthcare workers who have been investigators of Institutional Ethics Committee-approved research projects,except residents and faculty,and are still a part of the institute have been included in the study.The study was approved by the Institutional Ethics Committee of AIIMS,Rishikesh.We used descriptive analysis and the Chi-squared test to analyze data.P value<0.05 was considered significant.RESULTS Out of 59 participants,only 11(18.6%)were certified for GCP.Most of the participants(64.4%)had“Average”knowledge,33.9%had“Good”knowledge and 1.7%had“Poor”knowledge.Only 49%of participants had satisfactory practices related to GCP.There was a significant difference in the knowledge based on the current academic position for the items assessing knowledge of institutional review board(P=0.010),confidentiality&privacy(P=0.011),and participant safety&adverse events(P<0.001).There was also a significant difference in knowledge of research misconduct(P=0.024)and participant safety&adverse events(P=0.011)based on certification of GCP.There was a notable difference in the practices related to recruitment&retention on the basis of current academic position(P<0.001)and certification of GCP(P=0.023).We also observed a considerable difference between the knowledge and practices of GCP among the participants(P=0.013).CONCLUSION Participants have basic knowledge of GCP but show a lack thereof in certain domains of GCP.This can be addressed by holding training sessions focusing on these particular domains.

The Problems and Countermeasures of Four Community Pharmacies on Drug Quality Management in Kangping County

Objective To study the drug quality management of four community pharmacies and provide countermeasures and suggestions for improving the drug management level in Kangping County.Methods Literature research and investigation research were adopted in this paper to analyze the current situation and problems of drug management in four community pharmacies in a town of Kangping County.Results and Conclusion The problems of four community pharmacies in a town of Kangping County are low level of drug quality management,insufficient quality and capability of the practitioners and physician’s illegal act such as some licensed pharmacists paid from the linked pharmacies.There are also problems in facilities and equipment,drug display and storage,and document management,which reflects the lack of local drug supervision.Based on the above problems,some countermeasures and suggestions are put forward to strengthen the drug quality management of four community pharmacies in Kangping County.

Pursuing the Distilled Good Practices to Improve the Quality of Environmental Impact Assessment Reports and Hence Enhance the EIA Effectiveness and Help Address the Concerns of Project Proponents:An Indian Context

Despite a wealth of literature on the different facets of the EIA,and copious theoretical knowledge and practical experience,the general agreement is eluding definitions of EIA effectiveness,quality,and good practices.There are apprehensions about EIA meeting its basic objectives while project proponents continue to treat EIA as an impediment to development.Governments tend to adopt a“practical”approach,sacrificing pillars of EIA and overlooking the prime objective of environmental protection.Based on an extensive literature study and the author’s long EIA-related experience,some key workable practices for the EIA process are elaborated.Meticulous scoping using different sets of lenses,spotlighting significant impacts to determine the breadth and depth of EIA reports for focussed EIAs,robust EIA review and decision-making,commitment from the regulators for environmental protection,and use of strategic planning,strategic environmental assessment,and tiering practices are expected to address scholars’apprehensions and project proponents’concerns.

Cell sheet technology for regeneration of esophageal mucosa

The progress of tissue-engineering technology has realized development of new therapies to treat various disorders by using cultured cells. Cell-and tissue-based therapies have been successfully applied to human patients, and several tissue-engineered products have been approved by the regulatory agencies and are commercially available. In the review article, we describe our experience of development and clinical application of cell sheet-based regenerative medicine.Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been shown to be useful for removal of gastrointestinal neoplasms with less invasiveness compared with open surgery, especially in esophageal surgery. However, postoperative inflammation and stenosis are major complications observed after intensive mucosal resection. Therefore, we have developed novel regenerative medicine to prevent such complications and promote wound healing of esophageal mucosa after EMR or ESD. Transplantable oral mucosal epithelial cell sheets were fabricated from patients' own oral mucosa. Immediately after EMR or ESD, fabricated autologous cell sheets were endoscopically transplanted to the ulcer sites. We performed a preclinical study with a canine model. In human clinical settings, cell culture and cell sheet fabrication were performed in clean rooms according to good manufacturing practice guidelines, and pharmaceutical drugs were used as supplements to culture medium in place of research regents used in animal study. We believe that cell-based regenerative medicine would be useful to improve quality of life of patients after EMR or ESD.

Contribution of Good Agricultural Practices to Soil Biodiversity

At present time when climate change has negative effect on soil moisture and can decrease significantly the productivity, good agricultural practises have a high importance via their direct influence on soil properties, regimes and biodiversity. Objectives of this study have been focused on the assessment of good agricultural practises in different soil cultivation types: conventional, minimum till, mulch, no-till and organic farming. Method used was based on two case study areas where organic and/or minimal farming systems have been applied. As a control, we chose soil with traditional cultivation. In organic farm, we evaluated earthworms;their amount and status and in farm with different types of cultivation we evaluated the microbial activity to assess the biodiversity conditions. Basic soil properties and soil structure have been set to be able to assess the influence of good agricultural practises on soil environment. Our study shows positive effect of these practises on soil moisture content, biodiversity and soil structure stability. These findings can be used for further studies determining the ways of soil cultivation in harmony with nature—in sustainable way.

Assessment of Good Agricultural Practices on Cocoa and Coffee Farms in Northern Haiti

Haiti is the poorest country in the Western Hemisphere and presents a unique scenario for the food and agriculture industry, because there is no food safety legislation. The application of Good Agricultural Practices (GAPs) leads to improvements of quality, safety and sustainability of agricultural products. The purpose of the study was to assess the status of Good Agricultural Practices (GAPs) in cocoa and coffee farms in Northern Haiti. A general survey captured information about the farmer and the farm, and an audit checklist was used to assess compliance to GAPs. A total of 11 farms (n = 11) were audited, of which 7 were cocoa farms (64%) and 4 were coffee farms (34%) in the regions of Dondon, Limonade and Milot. Average overall audit scores for coffee farms (73%) were higher than for cocoa farms (55%). Farms affiliated with a cooperative scored higher (78%) than those that were not part of a cooperative (55%). The sections of the survey on “Practices related to premises and production site”, and the “use of agricultural inputs and chemicals” received the lowest scores but were confined to the cocoa farms. “Record keeping” plus “distribution, transportation, and traceability” were cause for concern with both the cocoa and coffee farms. Critical non-conformances included the access of livestock animals and domestic pets to processing and storage areas, the lack of control in the application of agricultural chemicals, a lack of safeguards on equipment and elevated surfaces, and washing of fresh cocoa beans to remove the mucilage with water that had not been treated or tested for potability. The root cause of the non-conformances, regardless of the commodity, was either related to poor physical and organizational infrastructures, or to a lack of technical training.

Milk Quality in Dual Purpose Cattle with Hand or Machine Milking

To evaluate and improve the milk quality in dual purpose cattle with hand or machine milking, a good management and sanitary program was implemented （GMSP） in 40 farms. Was obtained a diagnostic by an interview and in situ evaluation of management conditions and milk samples for laboratory analysis integrating the platform and microbiological counts, before and after of GMSP. The changes achieved were no significant （P 〉 0.05） for pH and density, but alcohol and foreign material were positive modified （P 〈 0.05） by GMSP in both hand and machine milking. The quantities of sediments were decreased （P 〈 0.05） in more than 50.0%. Decrease （P 〈 0.05） was observed in the counts of CFU mL1 （colony forming unitsl） in aerobic mesophilic, coliforms, Salmonella ssp. and Staphylococcus aureus with the GMSP. After GMSP Salmonella ssp. incidence was affected （P 〈 0.05） by hand （55.5%） vs. machine （61.5%） milking type; coliforms count and positive incidence in milk were affected （P 〈 0.05） in hand （81.5%） vs. machine （53.9%）. Therefore it was confirmed that the implementation of adequate sanitary and management practices, in both hand and machine milking, decreased the presence and incidence of microorganisms in milk with potential to produce disease in animals and humans.

Animal Welfare in the Uruguayan Veterinary Profession Field

Training and dissemination of good handling practices are key points in reducing animal abuse. Three aspects are considered in the development of education in animal welfare （AW）： （1） introduction of AW in curricular education, nevertheless it has not been applied in the Facultad de Veterinaria, Universidad de la Repfiblica de Uruguay, up to now; （2） promotion of permanent education for graduates; （3） development of plans for dissemination, follow up, assessment and continuous improvement on AW affairs. Aiming to obtain information about the knowledge of veterinarians on AW during the practice of their professional duties, in September 2016, an on-line questionnaire was sent to the veterinarians who were in the Educaci6n Continua database. The questionnaire had four sections： a general gathering information and three additional sections, one for each veterinarian professional field （large animal＇s health and production, small animal＇s health and food industry）. From 1,804 questionnaires sent, 388 answers were obtained. There were 69% attended at least one AW course, and 89.9% were willing to attend another AW course. And 63.5% considered the information received to be very useful for their daily activities, 95% considered that AW should be included in the veterinary studies curriculum, while 53.3% declared not having knowledge about the regional animal welfare strategy （RAWS）. The majority of the veterinarians considered the acquired knowledge very useful and are eager to obtain more information. It is necessary to keep working to include AW in the veterinary studies curriculum as well as continuing with the diffusion of good practices and AW principles, based on the national and international norms.

Corporate Social Responsibility——From the Perspective of Polish Enterprises

Corporate social responsibility （CSR） is becoming more and more frequently emphasized part of management in the structure of Polish enterprises. These results from the fact that growing awareness of consumers, destructive impact of industry on the natural environment, economic scandals, unethical behavior among entrepreneurs, bring about redefining the principles of a business activity on the market by entrepreneurs. As a result of the above, such values as honesty, trust, or responsibility take on greater importance. Additionally, more and more often, Polish entrepreneurs pay attention to the influence of the company on the environment, the way the stakeholders are treated, while striving to maximize profit. The present paper looks into the subject of social responsibility from the point of view of Polish enterprises. To verify this objective, there was the analysis of the due literature performed, and also carried out the survey among 174 entrepreneurs running their business activity in the area of Southern Poland. The research tool used in the research was the questionnaire （PAPI and CAWI）. In the conducted research, there were factors analyzed referring to knowledge of social responsibility among the people holding both managerial and lower-level positions, in particular opinion, is it important for enterprises to be driven by ethical standards？ How to implement CSR in their structures？ How to understood concept of CSR？ What are the reasons for the implementation of CSR in the strategy of the company？ The considerations （both the theoretical and practical ones） confirmed that the Polish enterprises feel the increased need to implement the activities in the field of social responsibility, which, in the present conditions, constitutes an important part of running a business activity.

Scrutiny of Microorganisms in Fermented Milk Beverage and Water from Dairy under State Inspection

The aim of the study was to examine microorganisms in samples of fermented milk beverage and water from dairy under state inspection. In a dairy located in the Recôncavo of Bahia, fifteen samples of fermented milk beverage were collected, corresponding to three different batches, and six water samples, two from each point of use in the industry: Point 1—Sanitary barrier;Point 2—Internal faucet for cleaning surfaces and utensils;Point 3—Drinking fountain for employees. All samples were submitted to microbiological research of total coliforms, Escherichia coli and Aeromonas spp. In the water samples, there was also quantification of heterotrophic bacteria and analysis of free residual chlorine. The fermented milk beverage samples did not show growth of total coliforms, E. coli and Aeromonas spp. With regard to water, no sample showed measurable levels of free residual chlorine, while in the microbiological analysis the count of heterotrophic bacteria in the drinking water exceeded the limit established by legislation (5.6 × 102 CFU.mL-1). In addition, the water from the sanitary barrier revealed total coliforms above the allowed value (1.3 × 101 CFU.100 mL-1) and showed contamination by Aeromonas spp. (7.0 × 101 CFU.mL-1). Thus, it can be inferred that, although the fermented milk beverage did not present the investigated microorganisms, the water used by the industry showed microbial contamination, and due to its participation in the entire production process, water quality control is extremely important to prevent contamination of the food handler and the final product, preventing the spread of diseases and harm to public health.

Agriculture and Water Sources Protection Zones in the Czech Republic

The area of interest is located in the South Moravia Region at the confluence of the Jihlava, Oslava and Rokytn^i rivers. Ivan^ice spring area comprises a series of hydrologic boreholes, it is the main water source for water supply of Ivan^ice and Rosice towns and provides water for 30,000 inhabitants. The risk analysis was created on the basis of water quality monitoring, hydrogeological assessment and terrain exploration and a revision of protection zones was proposed. The spring area is situated in nitrate vulnerable zones and recently nitrate concentrations have been decreasing. Water quality evaluation results： high concentration of manganese and iron, sometimes higher concentration of ammonium and COD. This area is intensively used for agriculture and it is necessary to make a compromise solution during protection zones proposal, The regime in protection zones can not affect manganese and iron concentration （their origin is in the natural geological environment）. Therefore, water treatment plant is in operation and its modernization is proposed. Furthermore, the paper deals with spring area intensification construction of a new hydrologic borehole, and managed and unmanaged infiltration of surface water. The proposal of protection zones revision consists of reduction to a 2nd level protection zone.

A Delphi Approach to the Selection of Good Agricultural Practices （GAPs） for Resilience Enhancement for Dry Land Farmers in North-Western Nigeria

An earlier baseline study （Jellason et al. in preparation） has identified some of the key challenges faced by farmers and from that, appropriate Good Agricultural Practices （GAPs） have been selected for the environment the farmers find themselves in and based on a review of available literature. Farmer action plans for enhancing smallholder resilience, GHGs emission mitigation and food security for these dry lands were developed. Expert opinions on the applicability of the selected GAPs to inform farmer co-learning and to validate the suitability of these practices in a dry land context were sought through the Delphi study. Experts were also invited to offer suggestions for improvement of the training action plan. Two rounds of a modified Delphi survey were carried out with experts from diverse backgrounds and locations across the globe to solicit their opinion. Results show that experts＇ agreement was reached on most of the action plan items. The results and opinions obtained from the survey were reviewed and adapted into the action plan leading to the development of GAPs for the co-learning exercise.

Investigating Road Safety Management Systems in the European Countries: Patterns and Particularities

A road safety management (RSM) system can be defined as “a complex institutional structure that involves cooperating and interacting bodies which support the tasks and processes necessary for the prevention and reduction of road traffic injuries”. RSM should promote the road safety progress of the country. However, the details of this relationship are generally lacking. This study explored the RSM systems in European countries based on the information collected through interviews with experts and officials, in each country, and using a “good practice” criteria questionnaire. The dataset included 14 countries with fifty items related to five RSM areas: institutional organization;policy formulation and adoption;policy implementation and funding;monitoring and evaluation;scientific support, information and capacity building. Cluster analyses and correlations were used to identify country groups with similar RSM components, to recognize typical RSM structures if available and to examine the relationship between RSM and road safety performance of the countries. The findings showed that all the countries are different when RSM systems are considered as a whole, making it impossible to identify typical RSM structures or a single best working model at a national level. However, it is possible to compare countries when the RSM areas are considered separately, where the clusters of countries recognized by the study present the patterns common for those European countries. Across the analyses, a number of countries with a consistently higher and lower availability of the RSM components were identified, enabling a final countries’ ranking into a number of groups. The latter actually reflects the level of RSM in the country, in terms of its correspondence to the “good practice” criteria. A further analysis indicated a positive correlation between the higher level of the RSM system and better safety performance of the countries.

Modified mesenchymal stem cells in cancer therapy: A smart weapon requiring upgrades for wider clinical applications

Mesenchymal stem stromal cells(MSC)are characterized by the intriguing capacity to home toward cancer cells after systemic administration.Thus,MSC can be harnessed as targeted delivery vehicles of cytotoxic agents against tumors.In cancer patients,MSC based advanced cellular therapies were shown to be safe but their clinical efficacy was limited.Indeed,the amount of systemically infused MSC actually homing to human cancer masses is insufficient to reduce tumor growth.Moreover,induction of an unequivocal anticancer cytotoxic phenotype in expanded MSC is necessary to achieve significant therapeutic efficacy.Ex vivo cell modifications are,thus,required to improve anti-cancer properties of MSC.MSC based cellular therapy products must be handled in compliance with good manufacturing practice(GMP)guidelines.In the present review we include MSCimproving manipulation approaches that,even though actually tested at preclinical level,could be compatible with GMP guidelines.In particular,we describe possible approaches to improve MSC homing on cancer,including genetic engineering,membrane modification and cytokine priming.Similarly,we discuss appropriate modalities aimed at inducing a marked cytotoxic phenotype in expanded MSC by direct chemotherapeutic drug loading or by genetic methods.In conclusion,we suggest that,to configure MSC as a powerful weapon against cancer,combinations of clinical grade compatible modification protocols that are currently selected,should be introduced in the final product.Highly standardized cancer clinical trials are required to test the efficacy of ameliorated MSC based cell therapies.

Implementation of Food Safety Legislation in Catering Establishments in Latvia

The aim of the research was to evaluate overall quality of introduction of hazard analysis and critical control points （HACCP） prerequisites and HACCP procedures in catering sector in Latvia to reveal common problems that can provoke food-borne infection outbreaks. Certain quantitative indicators were defined and analyzed to conclude about characteristic trends related to implementation of food safety legislation. The state＇s monitoring data on surveillance of catering establishments were used. Fulfillment of legislative requirements in about 6,000 catering establishments was evaluated during time period of 2004-2009. The results of investigation were obtained with help of statistical analyses using MS Excel computer program. The results of the research suggest that most of catering establishments （e.g., 83.6% during 2009） meet the hygiene requirements only partly. Non-conformities regarding HACCP-based self-control procedures were fixed during 49.2% of inspections. The research reveals characteristic shortcomings that are established from year to year, e.g., improper hygiene of premises （established during 30%-40% of inspections, depending on the year）, poor hygiene of technological equipment （established during 27%-37% of inspections）, poor personnel hygiene （established during 11%-22% of inspections）, inadequate competence of food service personnel （established during 10%-35% of inspections）, as well as non-observance of cleaning-disinfection procedures and technological parameters for food processing （established during 11%-25% of inspections, depending on the year）. Actual shortcomings can lead to both the direct and the indirect cross-contamination of food. On the base of the research, it was concluded that further detailed assessment of potential food safety risks is relevant to establish risk-based monitoring activities in catering sector.

The Expanding Roles of Hospital Pharmacists in Clinical Drug Trials in China

Objective To aim at summarizing the role of hospital pharmacists in clinical drug trials in China against the background that hospital pharmacists have already involved in team-based patient care.Methods The roles and responsibilities of Chinese hospital pharmacists were listed and categorized.Results and Conclusion There has been an upsurge in clinical drug trials in China.Hospital pharmacists play increasingly important roles in all aspects of clinical trials,such as stakeholder liaisons,protocol developers,ethics committee members,research team members,study drug managers,and subject intervention agents.Hospital pharmacists are an integral part of a clinical drug trial multidisciplinary team.Their value is reflected in several pharmacist-led or pharmacist-participating clinical trials as well as the trial project management position within hospitals.Pharmacists should be the designers,researchers,managers and supervisors of clinical drug trials.We expect that all clinical trial projects will include hospital pharmacists in their research teams soon.

Statistical Analysis of Defective Items of Pharmaceutical Wholesale Enterprises

Objective To provide some references and suggestions for promoting the healthy development of pharmaceutical wholesale enterprises,improving the scientific supervision level of the drug regulatory department and ensuring the quality of drugs in the circulation.Methods Retrieving the items on the official websites of the national and provincial drug regulatory departments from 2017 to 2019 that didn’t meet the requirements of the 2016 edition of the Good Supplying Practice in pharmaceutical wholesale enterprises under various inspections,the defective items were summarized and analyzed,and further study of the changes of defective items was conducted.Results and Conclusion 908 pharmaceutical wholesale enterprises had definite defective items,and 218 items violated the Guidelines for On-site Inspection of the Good Supplying Practice,with a cumulative frequency of 3874 defects.Defective items with high-frequency mainly occurred in storage and maintenance,facilities and equipment,personnel and training,general rules and sales.The average defect frequency in each pharmaceutical wholesale enterprises increased year by year,but the proportion of serious defective items decreased significantly.It is recommended that based on improving drug quality,pharmaceutical wholesale enterprises should strengthen personnel training to enhance their awareness of quality responsibility.Besides,the drug regulatory department should increase inspection and crackdown on illegal business operations and the deception of pharmaceutical wholesale enterprises.