Yuan Hongmei,Zhang Wenfeng,Ma Junhong,Zeng Yingying,Meng Lingquan

(School of Business Administration,Shenyang Pharmaceutical University,Shenyang 110016,China)

Abstract Objective To study the identification method that aims at the research and development target and makes the limited resources be optimized.With the frequent occurrence of potential drug safety hazards and the vigorous development of biomedicine,China’s pharmaceutical cold chain is facing huge opportunities and challenges.Under this background,it’s vital to promote the research and development of Chinese pharmaceutical cold chain technology.Methods First,China’s pharmaceutical cold chain patents were sorted out through the literature research method and patent analysis method,de-noises and cleans the data,uses the international patent classification (IPC) numbers as the pharmaceutical cold chain technology.Then,the IPC number co-occurrence matrix was constructed.Third,UCINET was used to visualize,draw the IPC number co-occurrence network.After that,K-cores analysis was applied to initially screen the core technology so as to build a comprehensive evaluation index system to evaluate the core technologies.Finally,Condorcet voting method was used to integrate the evaluation results to identify the core technologies.Results and Conclusion Based on this method,it can provide theoretical guidance for the development and decision-making of Chinese pharmaceutical cold chain enterprises,helping them break through technical barriers and improving the efficiency of Chinese pharmaceutical cold chain logistics.

Keywords:pharmaceutical cold chain;patent analysis;IPC number co-occurrence;K-cores analysis;condorcet voting method

After the vaccine incident in Shandong Province,the government,enterprises and the public have paid more attention to drug safety during transportation.In order to standardize the practice of pharmaceutical cold chain industry,the government formulated stricter transportation standards for pharmaceutical cold chain.In addition,with the development of biotechnology in recent years,biological products occupy an important position in the pharmaceutical sales market,which further increases the demand for the pharmaceutical cold chain.However,the infrastructure and technology of medical cold chain logistics in China lag behind those of developed countries with a cold chain transportation rate of 30%.Besides,the whole cold chain transportation is less than 1%.Meanwhile,in developed countries,the cold chain circulation rate is more than 90%[1].In this context,technological innovation has become a necessary way of industry development.China should focus on the innovation layout of pharmaceutical cold chain technology industry,optimizing the resource allocation to strengthen the core technology research.

At present,most of the relevant studies on pharmaceutical cold chain are from a qualitative perspective.In 1894,American Albert and British J.A.studied pharmaceutical cold chain management,national standards,and the development of related technologies.In order to improve the quality assurance of vaccine distribution in the US public health program,American scholar Alan et al.[2]verified various vaccine packaging methods and provided materials suitable for vaccine packaging in different seasons.British scholar Harlanda C et al.[3]developed a model through e-commerce.Their results show that in order to achieve the safety management of drug transportation,it is necessary to integrate pharmaceutical cold chain management,health management and e-commerce.Spanish scholar Perianez Parraga et al.[4]analyzed the broken chain problem in the current pharmaceutical cold chain,and put forward a method to ensure the safety of pharmaceutical cold chain in the whole process from the perspective of logistics system.Wu Qinggang[5]used SWOT method to analyze the development features of China’s pharmaceutical cold chain industry.After revealing the problems in China’s pharmaceutical cold chain industry,he proposed some solutions.Feng Jian et al.[6]used patents and papers as data sets to conduct a biometrics analysis so as to present the industrial development status of China’s cold chain logistics.They studied the development trend of China’s cold chain logistics and made technical predictions.

Most of the researches are on the problems of cold chain logistics or its prospects.Although there are a few quantitative studies,they are not very specific to the medical cold chain logistics.Therefore,this article analyzed the invention patent applications or authorized patents in the field of pharmaceutical cold chain from 2000 to March 2019,identifying the core technologies to provide theoretical guidance for the development of China’s pharmaceutical cold chain.This method aims at the research and development goals so as to allocate the limited resources better.

1 Research design

1.1 Method

The core technology is the most important key technology component in an industry,which can affect the development of other technologies in this field,and support the development of this industry.Therefore,identifying the core technology is very vital for pharmaceutical cold chain industry[7].The core technology has the following three characteristics.First,it is highly related to other technologies and can influence or even determine the development of other technologies.Second,it is in the most critical position in this field.Third,it has high economic,technical and legal value and can promote the progress of this industry[8].Therefore,it is imperative to improve the technical level of pharmaceutical cold chain,increase R&D investment in core technology,and improve the efficiency of pharmaceutical cold chain transportation in China.

1.1.1 The international patent classification (IPC) cooccurrence network

70% to 80% of the technologies in the world come from patent documents,which have always been regarded as an important information resource for studying technology development and innovation.In addition,the IPC number of a patent is divided according to the function and application of the technical theme.According to the IPC number,the technical field to which the patent belongs can be obtained,so IPC is taken to represent the technology in this paper.Patented technology has the characteristic of cross-field innovation.One patent may involve many IPCs,or multiple IPCs can appear in one patent and form an interactive IPC cooccurrence network.The IPC co-occurrence network can be visually represented by UCINET social network analysis software.Each node in the network diagram represents an IPC,that is,pharmaceutical cold chain related technology.

1.1.2 Initial core technology identification through kernel principle component analysis (KPCA)

Due to the large number of nodes in the IPC co-occurrence network,the complex and diverse relationships between nodes and the complexity of the technology itself may obscure the relationship between core technologies.Degree centrality of a node represents the number of co-occurrences.The larger the node is,the closer it is to other nodes,which is more important for the network.The KPCA method is proposed by the American social network analysis master Seidman[9]who studied the internal structure of social networks.This method considers the strength of nodes and connections in the network.Through KPCA,several technical fields which are in the core position and closely connected with other nodes can be preliminarily screened out containing a large number of nodes and connections.The details are shown in Fig.1.

Fig.1 KPCA decomposition

1.1.3 Initial core technology evaluation through comprehensive evaluation system

A patent not only represents the technology,but also has economic and legal characteristics.Chinese scholars Wang Tiange[10],Luo Tianyu[11],and Yan Ming[12]respectively applied the comprehensive evaluation system of patent to the core technology identification in the fields of biotechnology,wind power generation technology and lysozyme technology.Therefore,this study constructed a core technology comprehensive evaluation system from the dimensions of technology,economy and law,and a number of secondary indicators under each dimension was set.See Table 1 for details.TOPSIS is a commonly used multi-objective decision analysis method,which is often used to calculate the weight of indicators.Since the assessment of the core technology in this study is a merit-based decision,TOPSIS is first used to determine the weight of each secondary indicator.Then the values of each dimension are calculated aswhereωirepresents the weight coefficient of indicatori,andσirepresents the variance of indicatori.

Table 1 Comprehensive evaluation system of the core technology

1.1.4 Core technology identification through Condorcet voting method

Condorcet voting method is to combine the evaluation results of candidates from different dimensions.In this article,each of the 4 IPCs is regarded as an election candidate,and each indicator is regarded as a voter.The specific operation method is as follows.

(1) Determine election candidates and voters;

(2) Rank the election candidates respectively under each indicator;

(3) Compare each candidate in pairs,calculate their“win”,“lose”and“tie”times,and build a pairwise comparison matrix;

(4) Calculate the score of each election candidate according to the matrix,and the one with the highest score is the winner.

1.2 Research framework

The patent data retrieved from the IncoPat database was used in this paper to establish a cooccurrence network based on the IPC number.After that,the KPCA method was used to initially screen out the core technologies in the scattered technical fields.Then,the core technology can be identified by using the comprehensive evaluation system andCondorcet voting method,which can help decisionmakers understand the current situation of technology development.Finally,they can identify the key points of R&D and formulate corresponding strategies.

Fig.2 Research framework

2 Research on identification of core technology of pharmaceutical cold chain

2.1 Data source

All the data comes from the IncoPat patent database.Since pharmaceutical cold chain patents do not constitute a separate classification in the IPC number,retrieval method is adopted.As to the patent search strategy,according to the patent research of previous scholars,cold chain,refrigeration,and freezing are mostly taken as abstracts and names.Drugs,vaccines and blood products are the main refrigerated ones for cold chain transportation.

The combination of the two methods determines the search formula as“TIAB=((drugs or vaccine or blood products) and (cold chain or refrigerated or frozen) and (logistics or transportation)) and (AD=(20000101 to 20190228))”.There are 464 patent data of invention patents that have been applied or authorized in China,and 289 patent data are left after processing.Therefore,the research object of this paper is 289 patent applications for inventions.

2.2 Constructing IPC co-occurrence network through UCINET software

According to the IPC number of patents,223 IPC numbers are extracted from 289 patent data,that is,the technology.Based on this,the 223 * 223 technology co-occurrence matrix is established,as shown in Table 2.Next,the matrix is imported into UCINET software for visual processing,and the technical co-occurrence diagram containing 223 nodes and 1 156 connections is obtained,as shown in Fig.3.Each node in the figure represents the IPC number,that is,the relevant technology of pharmaceutical cold chain.The larger the node is,the better the connectivity of the node will be.They are important to the network.Different colors represent different levels of connectivity.The co-occurrence network made by UCINET software can clearly show the overall characteristics of pharmaceutical cold chain technology co-occurrence network.Besides,the software can be used to calculate the density of the co-occurrence network.The density reflects the tightness of the connections between the nodes in the network.The density value is from 0 to 1.The closer the density value is to 1,the better the overall network connectivity.

Fig.3 IPC co-occurrence network

Table 2 IPC co-occurrence matrix

It can be seen from Fig.3 that some isolated points exist in the IPC co-occurrence network.The overall connection is relatively loose,indicating that most of the patented technologies applied by applicants are only for a specific field,and the technical coverage is narrow.The density and standard deviation of the co-occurrence network of this technology are calculated by UCINET as 0.036 2 and 0.354 4.Therefore,the density is low,the overall network structure is loose,the network connectivity is poor,and the overall IPC co-occurrence rate is low.It indicates that the research of pharmaceutical cold chain technology is mainly about one certain technical field.The reason is that pharmaceutical cold chain involves multiple disciplines such as engineering,transportation,and medicine.It is difficult for the researchers to take all of them into consideration.

Although there are some isolated nodes,it is undeniable that most of the nodes are still connected.In the middle part of Fig.3,there are a large number of nodes and connections,among which the green,red and pink nodes are closely related to other nodes,but at the same time,the relationship between the various technical fields is blurred,and the true core technology cannot be found.Therefore,we can perform KPCA on low-density co-occurrence networks to remove nodes with smallkvalues in the network.Then,several technologies with core positions and good connectivity can be found,and the core area of the cooccurrence network can be discovered.

2.3 Initial core technology screening through KPCA

Applying KPCA on the IPC co-occurrence network,we can start from 0 fork,and gradually eliminate nodes with fewer connections in the network.Then,we increasekby 1 and repeat the cycle.When thekvalue is 5,56 nodes with higher connection strength are obtained.The IPC number cooccurrence network with 56 nodes is shown in Fig.4,which is clearer than Fig.3.The network density has also increased from 0.036 2 to 0.179 1,and the connection between nodes in the IPC co-occurrence network is closer.After KCPA,the number of cooccurrence network nodes of the IPC number is 58,accounting for 26.01% of all nodes,and the number of connections is 592,accounting for 51.21% of all connections.It can be seen that the overall IPC number network is highly dependent on the 56 nodes,which are only distributed in 13 IPC sub-classes.See Table 3 for the technical topics,IPC and patent numbers are represented by each subclass.

Table 3 High correlation IPC distribution

Fig.4 IPC co-occurrence network with high correlation

This article takes the IPC number as the technical characterization.From the IPC number co-occurrence network and the high-relevance IPC distribution table after excluding weak connections,it is observed that most pharmaceutical cold chain technology patents are concentrated in three types of transportation technology,such as F25D cooling or cold storage equipment,B65D transportation containers,and A61G that is specially designed for patients.The number of patents contained in these three types of technologies accounts for 60% of the total patents of pharmaceutical cold chain,indicating they are the core technologies of pharmaceutical cold chain.In addition to the above technologies,there are also other technologies such as temperature measurement,portable medicine boxes,household medicine boxes,plastic materials and insulation layers,etc.However,the number of patents in this area is still small,and they are on the edge of the IPC co-occurrence network,whose co-occurrence rate is low compared with other technologies.

Through KPCA,pharmaceutical cold chain technology in the central core position in the network is selected,which is closely connected with other technologies.Besides,it currently has a large number of applications.However,it doesn’t mean that these technologies (called initial core technologies in this article) are the core ones in the pharmaceutical cold chain field.In addition,the initial core technologies should be evaluated from the dimensions of technology,economy and law.

2.4 Initial core technological evaluation through comprehensive evaluation system

In order to identify the core technologies in pharmaceutical cold chain technology field with high value of technology,economy and law from the initial core technologies,a comprehensive evaluation system of core technology is constructed to conduct technical evaluations on the three initial core technologies of A61G,B65D,and F25D.First,the TOPSIS formula is used to determine the weights of the secondary indicators of patent technology and patent economy,as shown in Table 4.Then,according to the patent data,the secondary indicator values of the A61G,B65D,and F25D are calculated respectively,and the secondary indicator values are counted to obtain the primary indicator values for evaluation.The evaluation results are shown in Table 5.

Table 4 Weights of secondary indicators

Table 5 Evaluation results of initial core technology

2.5 Core technology forecasting through Condorcet voting method

The Condorcet voting method is used to integrate the evaluation results of the above initial core technologies.Each technology is regarded as a candidate,and each indicator is regarded as a voter.Then,the different technologies in pairs are compared to determine the core technology.First,the technologies under each indicator are sorted according to Table 6,the Condorcet comparison matrix is shown in Table 7 and the value of Condorcet is shown in Table 8.According to Table 8,it can be seen that A61G wins 1 point and loses 1 point.B65D wins 0 point and loses 2 points.F25D wins 2 points and loses 0 point.Therefore,the final ranking of the three technologies is:F25D >A61G >B65D.F25D technology is superior to A61G and B65D,and it is in the core position of pharmaceutical cold chain.

Table 6 Ranking of technical evaluation indicators

Table 7 Condorcet comparison matrix

Table 8 Condorcet score table

2.6 Results

After the identification process,we find that F25D technology is the current core technology in the field of pharmaceutical cold chain.F25D refrigeration or cooling technology has 85 patents,accounting for about 30% of the total number of patents.In this category,a large number of patents are independent movable equipment with refrigeration and freezing technologies (such as refrigerators,incubators)and related technologies.The remaining patents are distributed in the loading,supporting or taking out technology of refrigerated drugs,cooling fluid circulation device,etc.This type of technology is the basis of pharmaceutical cold chain transportation and they should attract the attention of enterprises and governments.

3 Conclusions and suggestions

3.1 Conclusions

Based on previous studies,this article takes applications or authorized pharmaceutical cold chain patents from 2000 to 2019 as the research object.And then,patent analysis method is used to identify the core technologies of pharmaceutical cold chain industry.The following conclusions are drawn.

3.1.1 Pharmaceutical cold chain is an interdisciplinary field

There are extensive relationships among pharmaceutical cold chain technology fields.Not only are there many connections between the same types of technologies,but also there are strong connections between them.Therefore,a complex network structure is formed among technologies.However,the overall density is not large enough,and there are a few isolated nodes,indicating that most pharmaceutical cold chain technologies are concentrated in infrastructures such as equipment with cooling and refrigeration functions and containers used for transportation and storage,while other technical fields are rarely involved.This may be due to the fact that pharmaceutical cold chain technology involves multiple disciplines such as drug,logistics,and engineering with many research directions.So it is difficult for R&D to cover all of them.

3.1.2 The core technologies in pharmaceutical cold chain field are cold storage and freezing technology

The core technologies in the pharmaceutical field are related equipment such as refrigerators,cold storage rooms,cold storages,incubators,cold bags and other technologies used in the cold chain transportation and storage of drugs.The latest version of Good Supply Practice requires that pharmaceutical companies should be equipped with refrigeration,freezing storage and transportation facilities,and monitor the temperature and humidity in the process of storage and transportation of drugs in real time.They must ensure that the temperature and humidity in the process of storage and transportation of drugs are controlled within the specified range.

3.2 Suggestions

Based on the current development of pharmaceutical cold chain in China,the following suggestions are proposed to promote the technical level of pharmaceutical cold chain and improve the safety and effectiveness of pharmaceutical cold chain transportation.

3.2.1 Promoting industrial upgrading and strengthening industry-university-research cooperation

Advanced refrigeration and freezing technology is the foundation of pharmaceutical cold chain system,so it is necessary to strengthen the upgrading of the technology.Enterprises should strengthen the research and development investment in cold storage,refrigeration and other related core technologies based on their own business and financial status.At the same time,they should also absorb foreign advanced technologies to develop new cold storage and freezing equipment,such as refrigerated vehicles suitable for long-distance transportation.In addition,enterprises,universities and research institutions need to cooperate with increased investment in innovation,strengthening the transformation of innovation results,and promoting the upgrading of China’s pharmaceutical cold chain industry.

3.2.2 Developing new technologies to promote the allround development of pharmaceutical cold chain

While developing the core technologies,other pharmaceutical cold chain related technologies,such as transportation technology specifically for patients should be taken into account.Although they are currently at a marginal position with fewer patents,they have high technical values and they may become the core technology in the future.Therefore,enterprises must conduct comprehensive and multiangle R&D on pharmaceutical cold chain technology.Meanwhile,the government should also formulate polies to support these promising technologies,which can improve the overall level of pharmaceutical cold chain industry.When a specialized and integrated pharmaceutical cold chain logistics system is formed,it will ensure drug quality and curative effect in the process of transportation.

Most of researches on pharmaceutical cold chain start from external management,but few from the perspective of technologies.Fewer of them apply patent information to identify core technologies.Therefore,the advantage of this article is to use multiple methods to identify the core technologies of pharmaceutical cold chain from a patent perspective.However,there are some limitations in this article.On the one hand,the amount of data is not big.On the other hand,there is little subjective analysis from experts,which may lead to some misunderstandings.It is hoped that more data can be used in followup research,with more expert analysis for detailed information studies.