" The pharmaceutical industry is confronted with many different issues at the levels of logistics and supply chain management. Traceability is a paramount in the pharmaceutical sector. It is not only essential to ensure the quality of the product, but also, it is required to trace possible adverse reactions back to a given lot of drug product, its manufacturing and control. Traceability needs to be addressed at three stages. First, the source (supplier) and origin (e.g. chemical, microbiological, animal, human…) of raw and starting materials must be identified. These materials must be tested and found compliant with compendial requirements. Second, traceability must be ensured in-house, throughout the all manufacturing process, from starting materials to the drug product, through the drug substance and all intermediates. Third, traceability should be ensured downstream, from lot release by the company to patient's administration. Traceability within the industry (stage 2) is ensured through compliance with the requirements of the approved marketing authorization and with Good Manufacturing Practice, under the responsibility of the Qualified Person (QP). Practically, the pharma industries may rely on software that provides valuable support to the Pharmaceutical Quality System, ensuring full traceability (e.g. SAP ERP). Although less robust then the in-house traceability, the tracking of the raw and starting materials (stage 1) is also addressed by the pharmaceutical industry through procedures for vendor qualification and verification, suppliers' audits and approval. This exercise is also part of the regulatory requirements. By contrast, the traceability of the product after its release by the QP (stage 3) is no longer within the sole remit of the industry. The involvement of different stakeholders, from different institutions/countries makes the supply chain management especially challenging. This is particularly critical for vaccines since: (1) Most of them are sensitive to high temperature, to freezing or both. (2) They are distributed worldwide including Low- and Medium-Income Countries (LMICs), in which the good distribution practices and the cold chain are not always ensured. (3) They are intended for healthy subjects and as such, their quality and safety profiles need to be outstanding. (4) In most cases, they are intended for infants, a vulnerable population vested with an important affective load. (5) a lack of efficacy can go unseen for years since they have a preventive (and not a curative) action. It is estimated that vaccines save millions of lives each year (WHO, 2019). An improvement of the supply chain will reinforce their impact on public health and could thus putatively save even more lives. For all these reasons, the case study which is proposed here will consider the applicability of a distributed ledger technology (DLT) as a support to the supply chain of vaccines after their release (stage 3). On top of that, DLTs have also the potential to efficiently and rapidly trace back a pharmacovigilance signal (e.g. adverse effect following immunization, breakthrough) or a quality complaint to the vaccine lot(s), its/their distribution channels and conditions for distribution, its/their manufacturing process and control. Recently, DLTs and blockchain gained more attention among scholars in the area of supply chain management. For example, Yong et al. (2019), suggested using the blockchain to ensure vaccine authentication. Their analysis, which will be reviewed in the following section, focuses on the system architecture that such a system should adopt and did not elaborate further on the supply chain's stakeholders and their requirements. How does vaccines stage 3's supply chains work? UNICEF is a procuring agency that buys vaccines for deployment in LIMCs (Pagliusi et al., 2018). Typically, UNICEF addresses a purchase order to a vaccine manufacturer, which is requested to send a given number of doses to a country. Following the lot release performed by the QP, the vaccine leaves the manufacturer's warehouse for the airport in a refrigerated truck. Upon arrival at the airport, the package is taken over by the airport services and could be temporarily stored in the cold room. The package will then be loaded into an aircraft and transported to the recipient country. Upon arrival in the recipient country, the package will be taken over by the local airport services and could be temporarily stored in the cold room. Following custom clearance, the package will be transferred to the central store, usually located in the capital or in a main city. The package is then disassembled, and its content is redistributed in the country, through in-country transportation (refrigerated truck) until the district or regional store. The district store will perform an additional redistribution exercise and then send the appropriate amount of vaccine doses to the in-country health centers, through local transportation (e.g. fridge box transported on motorcycle). Depending on the country distribution network, an additional step of redistribution and transport to remote dispensaries may be needed prior to the eventual administration of the vaccine to mother and child. Efforts are made to ensure traceability. This can be achieved more or less successfully for vaccines used in routine immunization. For these vaccines, the cold chain management is well organized, and the distribution channels are rather effective. However, clearly, there is room for improvement. For instance, it is not uncommon to record a quality complaint about a vaccine lot for which no information about its storage condition is available (e.g. a common issue comes from the unreported freezing of vaccines). As for the vaccines not to be used routinely, that are vaccines used in special settings (for example, outreach to homes (pregnant women, vaccine at birth dose) or schools (papilloma virus immunization of teenagers) or outbreak response (vaccination against cholera following flood disaster)), ensuring the traceability is much more challenging. In this case, there is an evident need for an easy-to-use and reliable tool for tracking the distribution and the storage conditions of the vaccine. We have noted that two vaccines of Pfizer Belgium, namely Prevenar 13 and Nimenrix are prequalified by the WHO (WHO, 2020). It was also noted that Pfizer is currently developing a vaccine for prevention of neonatal Group B streptococcal infections by maternal immunization (NCBS). Whereas the two former vaccines are intended for routine vaccination, the latter clearly ranks in the category of vaccines to be used in special settings. Moreover, the fact that (part of) the clinical development is performed in South Africa (ref. clinical trials) suggests that this vaccine could be used in LMICs. We believe that decentralized ledger technologies could prove to be a valuable (not to say essential) tool for the pharmaceutical industry and, more generally speaking, for public health strategy. The supply chain of vaccines appears as a preeminent case study not only because of the putative impact on the good distribution of these lifesaving medicines but also because of the rather large number of stakeholders and distribution intermediaries involved in their supply. Finally, the Group B streptococcus vaccine present in the pipeline of Pfizer Belgium appears as a model that could especially benefit from the implementation of a decentralized tracking system. ● Buurman, E. T., Timofeyeva, Y., Gu, J., Kim, J. H., Kodali, S., Liu, Y., ... & Singh, S. (2019). A novel hexavalent capsular polysaccharide conjugate vaccine (GBS6) for the prevention of neonatal group B streptococcal infections by maternal immunization. The Journal of infectious diseases, 220(1), 105-115. ● Pagliusi, S., Dennehy, M., Kim, H., & DCVMN AGM Organizing Committee. (2018). Vaccines, inspiring innovation in health. Vaccine, 36(48), 7430-7437. ● WHO: ● (2020) Prequalified Vaccines. (n.d.). Retrieved February 23, 2020, from https://extranet.who.int/gavi/PQ_Web/Default.aspx?nav=2&AspxAutoDetectCookieSupport=1 ● (2019) The power of vaccines: Still not fully utilized. (n.d.). WHO; World Health K?KOrganization. Retrieved February 23, 2020, from http://www.who.int/publications/10-year-review/vaccines/en ● Clinical Trials (). Trial To Evaluate The Safety, Tolerability, And Immunogenicity Of A Multivalent Group B Streptococcus Vaccine In Healthy Nonpregnant Women And Pregnant Women And Their Infants—Full Text View—ClinicalTrials.gov. (n.d.). Retrieved February 15, 2020, from https://clinicaltrials.gov/ct2/show/NCT03765073"
Publication References: Laurier, W. (2019, November). Blockchain Value Networks. In 2019 IEEE Social Implications of Technology (SIT) and Information Management (SITIM) (pp. 1-6). IEEE. Laurier, W., & Poels, G. (2012). Track and trace future, present, and past product and money flows with a resource-event-agent model. Information systems management, 29(2), 123-136. Laurier, W., & Poels, G. (2013). Invariant conditions in value system simulation models. Decision Support Systems, 56, 275-287. Polovina, S., von Rosing, M., & Laurier, W. (2014, July). Conceptual structures in LEADing and best enterprise practices. In International Conference on Conceptual Structures (pp. 293-298). Springer, Cham. Laurier, W., Kiehn, J., & Polovina, S. (2018). REA 2: A unified formalisation of the Resource-Event-Agent ontology. Applied Ontology, 13(3), 201-224.
Comment: The summary above was written by Bruno Fauconnier, who is still looking to get his timely, highly relevant and potentially high-impact project funded. It could also be generalised to a multitude of other domains.
Wim Laurier, Chargé de cours