A Novel Structure of Blockchain Applied in Vaccine Quality Control: Double-Chain Structured Blockchain System for Vaccine Anticounterfeiting and Traceability.

Background: Vaccine, as an irreplaceable means in herd immunization, is widely applied in prevention for communicable diseases. However, adverse impacts were frequently incurred by fake or expired vaccines in China. Given the necessity of vaccine anticounterfeiting, blockchain-based transaction platform could be practiced as a solution in addressing the issue; however, most of the available experiments focused on single-chain structured design with inventible limitations. Accordingly, exploration for the effectiveness and feasibility of mixed-chains structured platform for vaccine anticounterfeiting and tracing is essentially required.
Methods: Both public chain and private chain were inserted in anticounterfeiting and tracing platform designing process, which were subsequently simulated in Ethereum environment.
Results: By recording different information in public chain and private chain, partial information privacy protection requirements are realized. The transfer identification module realized the function of vaccine quality supervision and solves the problem of EPC label replication. Discussion. Compared with the traditional single-structured design, completeness information could be visited by all stakeholders in double-chain structure, including vaccine suppliers, National Medical Products Administration (NMPA), vaccine purchasers, and the vaccinated.
Conclusion: Double-chain structured system for vaccine anticounterfeiting and tracing is more effective.

1. Introduction

The anticounterfeiting and traceability system for vaccines has become an increasingly superior health issue because of pseudo-vaccine events that incurred high occurrence frequency of corresponded adverse events beyond tolerance [1]. As an important means of herd immunization program and an irreplaceable part of primary care for the whole population, the effectiveness and safety of the qualified vaccine, approved by National Medical Products Administration (NMPA), have been verified by a large number of Randomized Controlled Trials (RCTs). However, in real-world settings practice, profit-seeking incentivized suppliers of vaccines tend to evade the official assessment for effectiveness and safety of their products so as to reduce the cost of research and development (R&D) and manufacturing [2], which significantly increased the prevalence of unexpected adverse events accordingly.

Notably, it is suggested that the current counterfeiting detection system available illustrates insufficient capability in the unqualified vaccine identification as well as the traceability, which makes the intolerable profit-seeking behavior possible. Taking the pseudo-vaccine event of Changchun Chang sheng Biotechnology in 2018 as an example, pseudo-vaccines, 250,000 pieces at minimum, were counted prescribed in different provinces through fake packaging [3] with unreasonable serious adverse events cases, even blindness, reported by more than 50,000 vaccinators. Therefore, in order to address such health burden caused by pseudo-vaccines, the anticounterfeiting and tracing system was necessarily required for the whole-scope vaccine supply chain with all stakeholders involved [4]. As the current supervision system failed in detecting the fake packages as well as vaccine tracing, the novel system could be suggested to improve from aspects of transparency, traceability, and credibility.

In terms of the possible solutions with the ethical issues considered (e.g., confidential requirements for patients' medical information), blockchain, which shows superiority in information storage and traceability as well as the information confidentiality, is suitable in this scenario. Besides, blockchain could be inserted in the Internet of Things so that the production and delivery process of vaccines could be traced and the efficiency of supply chain management tends to be improved. Based on the key needs proposed by primary health care and population health care system in China, the corresponded requirements for establishing a blockchain-based vaccine anticounterfeiting and traceability system could be summarized as follows:

The information must be traceable.

The safety and transparency of vaccine trading information must be ensured.

The privacy of vaccinators should be guaranteed while the information security and openness are ensured.

The system should have credibility.

The system should be sufficiently secure to resist attacks.

According to the summarized requirements, the main research questions of this study are as follows:

How to establish a vaccine anticounterfeiting traceability system and quality supervision system meeting the above conditions?

How to protect the privacy of vaccinators given the requirement of traceable information openness?

2. Literature Review

In accordance with the current structures of vaccine anticounterfeiting and traceability methods available, this section systematically revisits the key technologies employed in the novel system design, including technologies of Internet of Things and blockchain, so as to accurately target the gaps between actual needs and technical limitations.

It is noted that the decentralized trend of data storage challenges the previous centralized management mechanism of Internet of Things. Therefore, assisted with blockchain, the feasibility of data storage in edge and terminal devices is ensured for the Internet of Things to effectively manage the previous centralized systems. In other words, Internet of Things could be seemed as the information receptor with the blockchain as the instruction for information storage, both of which constitute the basic structure of the system model.

2.1. Internet of Things Technology

As the information receptor, Internet of Things identifies the information through Radio Frequency Identification (RFID) and the information will be simultaneously transmitted to the redescribed language in light of Electronic Product Code (EPC).

2.1.1. RFID

RFID is a noncontact identification technology with radio frequency (RF) utilized in target objects detection in accordance with the principle that the electromagnetic field is formed by the fixed-frequency RF range transmitted by the receptor [5]. When the electronic tag passes through the area, it is excited to transmit the information stored in the electronic tag by inducing the energy formed by the current. Subsequently transferred to readers, information is practicable to be stored in the database [6].

2.1.2. EPC

As an electronic product labeling technology with coding technology, Electronic Product Code (EPC), usually employed as the information reference, is constituted by RFID and network technology. Through the middleware of EPC, the RFID code detection and transition to the object name resolution service are feasible to be implemented [7]. The specified entity information is described by physical markup language (PML) also used as the description language for the service that forms EPC information services (EPC IS). From EPC IS, the object name service (ONS) instructions are employed to support the saved files searched and copied via EPC middleware that subsequently transmits vaccine related information to supply chain. Notably, the requirement for automated network service is proposed for ONS to illustrate the linkage between vaccine information, EPC code, and the stored IP address on the automated network [8].

2.2. Blockchain

As a distributed database linked by multiple structured data blocks which store data in unforgeable format, blockchain is formed as the combination of hash function, asymmetric encryption technology, and consensus algorithm. Blockchain could be characterized by high reliability, data integrity, decentralization, and distrust [9]. As a distributed accounting system, it is implemented in light of multinode collective maintenance, point-to-point transmission, encryption algorithm, and consensus mechanism. A blockchain consists of several blocks to individually store transaction data or messages. The processed messages in the block are analyzed through hash function with the corresponding hash value obtained subsequently. Both transaction information and hash value are stored in the format of Merkle tree structured block [10].

Currently, the mainstream blockchain systems supporting smart contracts include Ethereum, codius, and hyperledger. Ethereum is the most widely used public chain system which provides a decentralized Ethereum virtual machine to handle smart contracts and has Turing completeness. The execution of the functions in the Ethereum contract requires a certain transaction cost gas. The operation principle of smart contract on Ethereum is shown in Figure 1. First, the Ethereum client sends the instruction to call the contract function to the Ethereum node. Subsequently, the Ethereum node inputs the instruction into its local Ethereum virtual machine, executes the instruction according to the contract rules, and returns the result; finally, the Ethereum nodes compare and verify the operation results and record the results to the chain according to the system consensus mechanism.

Figure 1

Execution principle of smart contracts on Ethereum.

2.3. Application of Blockchain

Based on the requirement for information disclosure level, blockchain could be specified as public chain structure that unfolds all information stored and the private chain structure is permitted to make all information maintain secrecy. Generally, in context of anticounterfeiting and traceability, the public chain or private chain is separately employed, which means the double-chain structured system is underexplored. The detailed analysis is individually given for both structures in the following subsections.

2.3.1. Public Chain Structured System

The public chain has many application examples in the anticounterfeiting traceability, which provides support for the utilization of public chain structured design in anticounterfeiting of vaccines [11], explores the influence of block-chain technology on the supply chain management, and analyzes the key impact factors of profit-seeking incentives of blockchain application in Malaysian enterprises by using the high credibility of public chains, implying that the delayed point-to-point payment is effective in the reduction of pseudo-vaccine frequency. The authors in [12] applied blockchaining technology to vaccine information forgery and recorded vaccine information in public chain, which achieved the traceability of vaccine information. However, the privacy of patients' sensitive information related to health status tends to be challenged because of the requirement of information disclosure when public chain applied [13].

2.3.2. Private Chain Structured System

Private chain is widely used in anticounterfeiting traceability, especially in privacy protection. [14] proposed the application methods of supply chain anticounterfeiting management mechanism based on private chain and smart contract and applied private chain to supply chain anticounterfeiting. Given that [15] explored the application of private chain in the scenario of enterprise manufacturing anticounterfeiting, whereas [16] applied blockchain technology to the traceability of supply chain, their conclusion provided a basis for private chain to record vaccine information and realize anticounterfeiting and traceability of drug supply chain. Furthermore, based on the results found by [17], it is possible to combine blockchain technology with vaccine production supervision, implying the feasibility of obtaining vaccine production management monitoring with private chain node scalability and privacy protection by using private chain authority at the same time [18]. However, these research schemes have the problem of low credibility because of the single decision point of private chain structure.

3. Double-Chain Structured System

Based on the above limitations, public chain and private chain solutions may be used for vaccine data storage and vaccinator privacy protection. In addition, adopting the scheme of delaying the point-to-point payment of vaccination costs in the transfer identification module may realize anticounterfeiting and quality supervision of vaccines. Traditional vaccine anticounterfeiting traceability uses batch serial numbers, and serial numbers and vaccine information are stored in a database. But there are still four problems that cannot be solved:

There is the possibility of forgery in the numbering of traditional numbers.

Data stored in a traditional database can be tampered with.

Because the database is a centralized server, it is more likely to be attacked and its stability is at risk.

To solve the above four problems, we propose a hybrid double-chain anticounterfeit traceability system. It is composed of traceability module and transfer identification module. The overall framework is shown in Figure 2.

Figure 2

System architecture.

3.1. Traceability Module

Therefore, our system solution will be designed around the above four problems. RFID (Radio Frequency Identification) technology will be applied throughout the vaccine supply chain to solve the problem of label counterfeiting. In our system, each vaccine is assigned an EPC (Electronic Product Code), which is written into the RFID tag. During the vaccine supply chain phase, each party query RFID and adds its own unique evidence to the tag so that the next party can check whether the product has passed through the legitimate supply chain. If any discrepancies are found on the label, the vaccine can be considered a knockoff.

In order to solve the other problems mentioned above, we adopt the blockchain architecture for data storage [19]. The information stored on the blockchain is nontamperable, which significantly reduces the possibility of data being tampered with. Blockchain is a decentralized structure system, which can avoid the attack of the central node, and thus the stability of the system can be guaranteed. Our system improves traceability accuracy by recording information on the blockchain from production to vaccination. The architecture is shown in Figure 2.

3.2. Transfer Identification Module

However, such a solution cannot solve the following problem: EPC labels are copied. When an EPC tag is copied, it is not possible to identify the authenticity of a vaccine by means of an RFID tag query.

Our system uses the private chain account balance mark for anticounterfeiting, creates an account for each vaccine corresponding EPC label after the inspection department passes, and records in the transfer module of the intermediate system. Medical Account will transfer ETH (Ethereum virtual currency) to EPC account after the safety period after inoculation. The transfer node in the private blockchain will regularly inquire about the EPC account of the transfer module and remind the vaccine buyer to transfer to the vaccine manufacturer if its balance is >0.

When a vaccine manufacturer copies a fake vaccine with a real EPC label, it will pass anticounterfeiting checks for vaccines. However, before the inoculation, an account for the corresponding EPC label will be created in the private chain. At this time, the system detects that the account for the corresponding EPC label already exists in the private chain. At this point, you just need to check the account balance. If the balance of > is 0, it means that the vaccine corresponding to the EPC label has been inoculated and the vaccine payment has been settled, and the same EPC label with the same is a counterfeit. If the balance is 0, it means that the vaccine corresponding to the EPC label has passed the inspection process but the incubation period has not yet ended, and the vaccine will be sent for manual inspection. The information of the vaccine corresponding to the previous EPC label will also be traced and checked.

That is, we have realized the “point-to-point” account between the vaccine and the private chain. Since an EPC code corresponds to an account in the private chain, we can quickly know the authenticity of the vaccine by checking the balance of the EPC code tag account corresponding to the private chain. Manufacturers who produce fake vaccines will be recorded in the record module of middleware system and remind buyers in subsequent vaccine transactions. In the payment module, the implementation details will be described in detail.

3.3. Scenario Analysis

Vaccines go through the following stages from production to injection: production, inspection, storage, transportation, and injection. The information generated by each link will be entered into our system through the Internet of Things technology [20]. Our double-chain system records information from each part of the vaccine supply chain and stores the information in blocks of the public blockchain. For the vaccination link information that needs privacy protection, we will save the information on the block of the private chain, so as to meet the requirements of anticounterfeiting traceability and privacy protection of vaccines at the same time.

Our system covers all stages of the vaccine supply chain, including production, inspection, storage, transportation, and injection. In order to better show our solution, we put production and inspection and storage in the transportation stage together, so as to better understand our system design.

3.3.1. Production and Inspection

Information about the vaccine production process will be recorded on the public blockchain. Because the information is public, it is stored in the public blockchain for easy access by any regulatory authority. CDE can access the block where the production information is stored at any time to view the information, so as to realize the real-time inspection of vaccine production enterprises. The recorded information is shown in Table 1.

Table 1

Vaccine batch production record and examination record.

Vaccine batch production record	Vaccine batch examination record
(i) Vaccine name	(i) Vaccine name
(ii) Vaccine batch number	(ii) Vaccine batch number
(iii) Vaccine specifications	(iii) Vaccine specifications
(iv) The date of production	(iv) The date of production
(v) Quality guarantee period	(v) Inspection quality standard
(vi) Production information records	(vi) Check instrument information record
(vii) Production material information records	(vii) Examine temperature
(viii) Intermediate process information records	(viii) Examine humidity
(ix) Exception information records	(ix) Exception information records
(x) Hash of reviewer signature	(x) Hash of examiner signature
(xi) Extra details and information	(xi) Result of examine
	(xii) Extra details and information

3.3.2. Storage and Transportation

It is proved that the record of stored information of vaccine is an indispensable link in the traceability system of vaccine [21]. In addition, stored vaccines that do not meet GMP standard in the process of vaccine transportation are at risk of reducing the quality of vaccines, so the record of transportation link information is also a necessary submodule of vaccine traceability system. The recorded information is shown in Table 2.

Table 2

Vaccine batch storage record and transportation record.

Vaccine batch storage record	Vaccine batch examination record
(i) Vaccine name	(i) Vaccine name
(ii) Vaccine batch number	(ii) Vaccine batch number
(iii) Vaccine specifications	(iii) Vaccine specifications
(iv) The date of production	(iv) The date of production
(v) Quality guarantee period	(v) Quality guarantee period
(vi) The date of storage	(vi) Cold chain store temperature
(vii) Storage temperature	(vii) Cold chain store humidity
(viii) Is the storage in the dark	(viii) Exception information records
(ix) Exception information records	(ix) Hash of examiner signature
(x) Hash of reviewer signature	(x) Extra details and information
(xi) Extra details and information

3.3.3. Injection

The importance of recording information during the injection is heightened by disputes over improper practices by the inoculating doctors or the inoculators own abnormal reactions to the vaccine. The need to protect the privacy of vaccinators' personal information makes the system have higher requirements on the way to store the information in this link. If the vaccinators' information is stored in the public chain, it will result in the serious consequence that the personal information privacy of vaccinators will be disclosed. This system stores all the information recorded in the inoculation link in the private chain. Since the private chain is only open to authorized users, the privacy of inoculators can be sufficiently protected. The recorded information is shown in Table 3.

Table 3

Vaccinator record and injection record.

Vaccinator record	Injection record
(i) Vaccinator ID number	(i) Inoculated vaccine name
(ii) Vaccinator name	(ii) Inoculated vaccine specifications
(iii) Vaccinator sex	(iii) Inoculated vaccine batch
(iv) Vaccinator age	(iv) Date of vaccination
(v) Vaccinator past medical history	(v) Vaccination department
(vi) Vaccinator phone	(vi) Vaccination doctor
(vyii) Vaccinator address	(vii) Extra details and information
(viii) Extra details and information

3.3.4. Payment

This system has played the role of quality supervision for the payment. Through the virtual currency of the private chain in the system, the point-to-point account of vaccination institution, and vaccine EPC, the defective products in vaccines can be reduced fully, because the defective products will directly lead to the reduction of vaccine trading volume, or even zero [22].

During injection, if there is a problem with the quality of the vaccine, the vaccinator will have an abnormal adverse reaction within a period of time. If there are no abnormal adverse reactions due to vaccination during this period, the vaccine is considered to be qualified in quality [23]. Our system guarantees that vaccines with a qualified EPC label will only be allowed to be paid by vaccination institution to vaccine manufacturers if there are no abnormal adverse reactions during the period after vaccination.

In addition to the payment module under quality supervision mechanism, the fixed exchange rate could be obtained with no digital currency involved. The scheme of real currency transfers at the end of the quality supervision, it avoids unstable factors such as large exchange rate fluctuation between digital currency and real currency, which improves the stability of vaccine transaction.

In addition to the payment module under quality supervision mechanism, the fixed exchange rate could be obtained with no digital currency involved. The scheme of real currency transfers at the end of the quality supervision; it avoids unstable factors such as large exchange rate fluctuation between digital currency and real currency, which improves the stability of vaccine transaction. The process is shown in Figure 3.

Figure 3

System in payment period.

4. Simulation

The experimental hardware environment of this scheme is Intel (R) Core (TM) I7-7700HQ CPU @2.8 GHz and RAM 8 GB. The experimental software environments of this scheme are Geth-Windows-AMD64-1.9.0 and Ethereum-Wallet-Win64-0-11-2. The public blockchain uses Ethereum to access the main network node, and the private blockchain uses Ethereum to access the main network node. We use Python for writing business logic and developing intermediate systems. The interface framework uses QT. We use Web3J to connect the intermediate system to the blockchain, using version 3.4.0.

In order to handle the loss of requests, we use rabbitmq as a message queue. It ensures the order of requests and asynchronism of the system. If the message is lost, our message queue will call a callback function to notify the system. We will handle the lost request manually.

In this experiment, our system uses SpringCloud as a distributed framework, and experiments show that our system can resist the number of rabies vaccines even in the whole year of 2019.

Not only does SpringCloud provide the most basic components of a distributed framework, it also works well with other middleware. We use Eureka as a distributed registry. We use nginx to do server load balancing and achieve high availability of the system. Due to the strong middleware adaptation capability of SpringCloud, we can use different middleware to restrict any subsequent congestion caused by instantaneous traffic request, so our system has extensibility.

4.1. Data Structure

Our system uses struct form for vaccine information. Multiple strings of vaccine information are stored as struct. As shown in figure. This allows us to store a batch of vaccine information with just one call the add Info function. The struct is shown in the Figure 4.

Figure 4

Struct of vaccine information.

4.2. Vaccine Information Recorder

The Vaccine Information Recorder is responsible for the input of vaccine information into the system. Our system will call the interface provided by web3J framework, connect to Ethereum mining and generation node, and record the vaccine information stored in the structure into the block. The operation interface is shown in Figure 5.

Figure 5

Recorder operation interface.

We use the API provided by the Datetime package to calculate the time of the record Module of the intermediate system. The results are shown in Figure 6.

Figure 6

System average response.

According to the experimental data, when the number of private blockchain nodes is relatively small, our system maintains a response speed below 500 ms. However, as the number of private chain nodes increases, the response speed slows down. When the number of private chain nodes reaches 20000, the response time can still remain within 3000 ms. In China, for example, the number of batches of rabies vaccine in 2019 was 17,853, and the system is fully capable of handling this amount of data. In fact, as the amount of data increases, the private blockchain data can be sliced, which can greatly reduce the response speed.

4.3. Vaccinator

After a vaccinator gets the vaccine, check out the vaccine information. When vaccinator injects the vaccine, it will get the index number for its stored array, enter the number, and get the vaccine traceability information. The result interface is shown in Figure 7.

Figure 7

Vaccinator operation interface.

From the simulation experiment, it can be seen that our scheme has advantages like in Table 4 compared with [3].

Table 4

Novel plan comparison.

	Novel plan	Plan in [3]
Traceability links	Manufacture, examination, storage, transportation, injection	Manufacture, examination, injection
Information data structure	Struct	String
	Call a smart contract to store multiple pieces of information	Smart contract store is invoked multiple times
Privacy protection	The private chain stores vaccination information to protect patient privacy	All data is stored in Ethereum without privacy protection
Anticounterfeiting effectiveness	EPC fraud	EPC fraud
	EPC label replication
Quality supervision	Transfer after passing the incubation period, and check the balance of the account to complete the quality supervision	None
Transaction format	After quality supervision is passed, the money is transferred	Vaccine coin transfer
Cost	4 trade gas	3 trade gas

5. Discussion

5.1. Results Summary

Compared with the traditional single-structured design, completeness information could be visited by all stakeholders in double-chain structure, including vaccine suppliers, National Medical Products Administration (NMPA), vaccine purchasers, and the vaccinated.

5.2. Evaluation of the Functional Modules

Though increased cost was found in the novel system compared with the result shown by [3], accounting for approximately 1 gas, advantages could also be found in this scheme. For traceability, more comprehensive recorded information of storage and transportation could be tracked in this scheme, where traceability pathways suit more practicable scenarios compared with the scheme of [3]. Reduced by 90% of time spent, the simplified process of data calling from storage module is another significant improvement. As struct was utilized in vaccine related information storage, there is no need to call the smart contract storage function again. In contrast, [3] used string structured storage method for vaccine information where the smart contract expected to be called at least 10 times when searching vaccine related information. Additionally, utilization of privilege control inserted in private chain ensured the privacy of sensitive information for patients, which avoids the patients' medical information leakage, such as health status and injection frequency.

In terms of security, compared with the disclosure of all data in [24] scheme, we use the EPC code to correspond to the point-to-point account of the private chain to solve the security problem of EPC label replication. Quality supervision could also be implemented through this system. Compared with [24] without quality supervision scheme, the payment will occur when vaccine is identified as qualified with reasonable frequency of adverse events until the end of incubation period of vaccine injection. Subsequently, payments will be delivered for vaccine manufacturers after checking account balance to complete quality supervision.

5.3. Limitations

Although the system was designed to fully address the requirements of vaccine anticounterfeiting and traceability in the real-world settings as possible, limitations that potentially affect the system effectiveness inevitably exist. The internal reliability could be ensured for the patients' data stored; however, the external reliability, Ethereum environment, is expected to be attacked theoretically [25]. As the system simulation was conducted in such environment where the attack has been repeatedly reported, the suspicious safety remained as the issue to be solved, but the simulation excluded such possible risk from the hypothesis. Furthermore, similar risk could also be found in the web3j framework employed as connecting instruction to call the smart contract in Ethereum.

The large number of stream requests caused in an instant, that is, the system carrying capacity in the case of high concurrency, is an extreme situation that every system needs to consider. Since vaccine information is stored in a structured array, the corresponding array position will be returned at the end of input. In context of high concurrency, such as at the level of one million, the problem of data coverage tends to occur, implying that two batches of vaccine information are stored in one array position simultaneously and the latter data to cover the former might be incurred. However, for the applicable scenarios in context of this system where the frequency of concurrency is far less than one million, probability of concurrency is under tolerance.

6. Conclusion

This paper discusses the problems in the application of blockchain in vaccine anticounterfeiting traceability and designs a vaccine anticounterfeiting traceability system combining public chain and private chain. The problems of quality supervision and privacy protection in anticounterfeiting traceability of vaccines are solved. The experiment proves that our system has higher anticounterfeiting performance and more comprehensive traceability links than other vaccine anticounterfeiting traceability platforms, with more advantages such as privacy information protection and quality supervision.