Build a Sustainable Vaccines Industry with Synthetic Biology.

The vaccines industry has not changed appreciably in decades regarding technology, and has struggled to remain viable, with large companies withdrawing from production. Meanwhile, there has been no let-up in outbreaks of viral disease, at a time when the biopharmaceuticals industry is discussing downsizing. The distributed manufacturing model aligns well with this, and the advent of synthetic biology promises much in terms of vaccine design. Biofoundries separate design from manufacturing, a hallmark of modern engineering. Once designed in a biofoundry, digital code can be transferred to a small-scale manufacturing facility close to the point of care, rather than physically transferring cold-chain-dependent vaccine. Thus, biofoundries and distributed manufacturing have the potential to open up a new era of biomanufacturing, one based on digital biology and information systems. This seems a better model for tackling future outbreaks and pandemics.

The role of manufacturers in the implementation of global traceability standards in the supply chain to combat vaccine counterfeiting and enhance safety monitoring.

The counterfeiting of vaccines is an increasing problem globally with the safety of persons vaccinated, the trust in vaccines generally and the associated reputation of vaccine manufacturers and regulatory agencies at risk. This risk is especially critical with the on-going development of COVID-19 vaccines. The ability to track and trace vaccines through the vaccine supply chain down to persons vaccinated has to be enhanced. In this context of traceability, the global immunization community has recently set the barcoding of the primary packaging of vaccines, specifically vaccine vials and pre-filled syringes, as a top priority. Emerging vaccine manufacturers are already engaged in investigating ways to incorporate barcoding in their labelling and packaging using GS1 international standards. A specific pilot taking place in Indonesia by the national vaccine manufacturer, Bio Farma, shows the innovation of barcoding on primary packaging already underway with a relatively modest level of investment and success at this stage. This article highlights the efforts of industry and governments on the value of traceability and introduction to 2D barcodes. Access to financial resources and support from the international immunization community would accelerate such innovations leading to enhanced security of the vaccine supply chain.

An Efficient Double-Layer Blockchain Method for Vaccine Production Supervision.

A vaccine is a biological product which is an important means for human beings to protect themselves. Most of its users are young children with weak immunity. Once a vaccine has a problem, it will pose a serious threat to the lives of many people. At present, the supervision of vaccine production is very simple. The vaccine production record is completely controlled by the enterprises. Enterprises only submit production records to the supervisory agency for review when the vaccine needs to be sold. Production records are easily forged and modified. In order to solve the shortcomings of traditional centralized management. We propose a supervision method for vaccine production based on double-level blockchain. At first, we have designed a double-level blockchain structure. The first level is private data of vaccine prduction enterprise, including production records and corresponding hash. The next level is public data, including production records hash and vaccine information. In this way, we make vaccine enterprise to submit production records in a timely manner without fear of privacy leaks. We avoid enterprise tampering or falsification of production records through the non-tampering features and time stamps of the blockchain. To improve the time efficiency, we propose a consensus mechanism for multi-node cooperate. The primary supervisory node provides sorting services and verifies the correctness of the blockchain replica. The ordinary supervisory node can replace the primary supervisory node when necessary, and help the primary supervisory node recovers data in case of information loss. The review node is responsible for providing complete and correct blockchain copies for other nodes. So we can avoids the problem of waste of time resources in the traditional blockchain system. In addition, in order to avoid the waste of space caused by the redundancy of the blockchain, we propose a vaccine data cutting mechanism. We use the timestamp of the blockchain and the vaccine validity period to determine if the block can be cutted. At the same time, it is also possible to judge whether the block can be cutted based on the information exchange with the vaccination institution. Through these methods, we have realized spatiotemporal efficiency supervision of vaccine production. And for the time being, research work in the field of vaccine production supervision is still very rare. So Our work is ground-breaking.

Chile's National Advisory Committee on Immunization (CAVEI): Evidence-based recommendations for public policy decision-making on vaccines and immunization.

A National Immunization Technical Advisory Group (NITAG) provides independent, evidence-based recommendations to the Ministry of Health for immunization programmes and policy formulation. In this article, we describe the structure, functioning and work processes of Chile's NITAG (CAVEI) and assess its functionality, quality of work processes and outputs, and integration of the committee into the Ministry of Health policy process using the Assessment tool for National Immunization Technical Advisory Groups. Among its strengths, CAVEI's administrative and work plasticity allows it to respond in a timely manner to the Ministry of Health's requests and proactively raise subjects for review. Representation of multiple areas of expertise within the committee makes CAVEI a robust and balanced entity for the development of evidence-based comprehensive recommendations. High ranking profile of the Secretariat structure furthers CAVEI's competences in policymaking and serves as a bridge between the committee and international initiatives in the field of immunizations.

Study on the Procedure for Lot Release of Vaccines in Japan.

Biological products, such as vaccines, blood products, antitoxins, and antivenoms, are released into the market following a lot release conducted by National Regulatory Authorities or National Control Laboratories, even if their manufacturing and marketing have been authorized. Independent lot release by regulatory authorities is not a procedure unique to Japan, but is performed worldwide. Previously, Japan carried out lot release mainly by laboratory tests, and the manufacturers' in-house test records were used as a reference, not involved in the decision of lot release. Conversely, the international standard procedure promoted by the World Health Organization (WHO) includes a document review of the manufacturers' summary protocols, and laboratory tests are listed as an optional procedure. To harmonize with the WHO recommended international method, Japan modified the procedure and introduced a document review in addition to laboratory tests for vaccines in 2012. Since then, substantial knowledge regarding vaccine quality has been obtained during the process of summary protocol reviewing. Here, we outline the current status of the lot release procedure in Japan. We shed light on its history and show recent research based on the knowledge obtained from the protocol review to improve efficiency of laboratory testing and international harmonization.

Workshops advocating ASEAN Vaccine Security and Self-Reliance (AVSSR): A regional initiative.

The concept of ASEAN Vaccine Security and Self-Reliance (AVSSR) has recently been advocated for by the National Vaccine Institute (NVI), a public organization of Thailand, through two workshops in 2014 and 2015 organized in cooperation with the World Health Organization (WHO) for the ASEAN Collaboration Initiatives for Regional Vaccine Security and Self-Reliance (VSSR). In both workshops relevant policy makers, Expanded Programme on Immunization (EPI) managers, and experts from government and partner agencies involved in the vaccine life cycle actively participated. A paradigm shift in leveraging the initiatives of VSSR from national to regional levels was noted and reiterated. The first workshop's objective was to understand the perspectives and identify the needs of ASEAN countries regarding vaccine security, and to list potential areas for further collaboration. The existing vaccine-related capacities, collaborations, and networks in ASEAN were discussed based on findings from a pre-workshop, self-administered questionnaire survey. The workshop ended with four key areas unanimously recommended for regional collaboration strengthening: (1) system development for vaccine security; (2) human resource development; (3) ASEAN price policy for vaccine (APPV) and pooled procurement; and (4) communication and coordination. A call for immediate action was made, prompting the second workshop to focus only on "communication and coordination" to identify concrete, actionable collaborative models for effective communication and coordination. At the second workshop, a five-year Communication and Coordination Action Plan (CCAP) was developed to foster long-term AVSSR. The AVSSR's ultimate goal is to avoid incidental vaccine shortage and ensure sufficient supply of affordable, quality vaccines for normal and urgent situations both at the national and ASEAN-wide levels. To date, collaboration for AVSSR is being strengthened according to the ASEAN post-2015 Health Development Agenda and its collaborative framework among concerned countries and development partners. Nevertheless, to achieve the goal, integration of multiple strategies based upon strong policy commitment and uninterrupted engagement among relevant partners are required.

Tree-based scan statistic - Application in manufacturing-related safety signal detection.

BACKGROUND AND OBJECTIVES: Over the last decades, medicinal regulations have been put into place and have considerably improved manufacturing practices. Nevertheless, safety issues may still arise. Using the simulation described in this manuscript, our aim is to develop adequate detection methods for manufacturing-related safety signals, especially in the context of biological products. METHODS: Pharmaceutical companies record the entire batch genealogies, from seed batches over intermediates to final product (FP) batches. We constructed a hierarchical tree based on this genealogy information and linked it to the spontaneous safety data available for the FP batch numbers. The tree-based scan statistic (TBSS) was used on simulated data as a proof of concept to locate the source that may have subsequently generated an excess of specific adverse events (AEs) within the manufacturing steps, and to evaluate the method's adjustment for multiple testing. All calculations were performed with a customized program in SAS v9.2. RESULTS: The TBSS generated a close to expected number of false positive signals, demonstrating that it adjusted for multiple testing. Overall, the method detected 71% of the simulated signals at the correct production step when a 6-fold increase in reports with AEs of interest (AEOI) was applied, and 31% when a 2-fold increase was applied. The relatively low detection performance may be attributed to the higher granularity associated with the lower levels of the hierarchy, leading to a lack of power and the stringent definition criteria that were applied for a true positive result. CONCLUSION: As a data-mining method for manufacturing-related safety signal detection, the TBSS may provide advantages over other disproportionality analyses (using batch information) but may benefit from complementary methods (not relaying on batch information). While the method warrants further refinement, it may improve safety signal detection and contribute to improvements in the quality of manufacturing processes.

Preferences for health economics presentations among vaccine policymakers and researchers.

PURPOSE: Measure the preferences of decision makers and researchers associated with the Advisory Committee on Immunization Practices (ACIP) regarding the recommended format for presenting health economics studies to the ACIP. METHODS: We conducted key informant interviews and an online survey of current ACIP work group members, and current and previous ACIP voting members, liaison representatives, and ex-officio members to understand preferences for health economics presentations. These preferences included the presentation of results and sensitivity analyses, the role of health economics studies in decision making, and strategies to improve guidelines for presenting health economics studies. Best-worst scaling was used to measure the relative value of seven attributes of health economics presentations in vaccine decision making. RESULTS: The best-worst scaling survey had a response rate of 51% (n = 93). Results showed that summary results were the most important attribute for decision making (mean importance score: 0.69) and intermediate outcomes and disaggregated results were least important (mean importance score: -0.71). Respondents without previous health economics experience assigned sensitivity analysis lower importance and relationship of the results to other studies higher importance than the experienced group (sensitivity analysis scores: -0.15 vs. 0.15 respectively; relationship of the results: 0.13 vs. -0.12 respectively). Key informant interviews identified areas for improvement to include additional information on the quality of the analysis and increased role for liaisons familiar with health economics. CONCLUSION: Additional specificity in health economics presentations could allow for more effective presentations of evidence for vaccine decision making.

Assessment of temperatures in the vaccine cold chain in two provinces in Lao People's Democratic Republic: a cross-sectional pilot study.

OBJECTIVE: All childhood vaccines, except the oral polio vaccine, should be kept at 2-8 °C, since the vaccine potency can be damaged by heat or freezing temperature. A temperature monitoring study conducted in 2008-2009 reported challenges in cold chain management from the provincial level downwards. The present cross-sectional pilot study aimed to assess the current status of the cold chain in two provinces (Saravan and Xayabouly) of Lao People's Democratic Republic between March-April 2016. Two types of temperature data loggers recorded the temperatures and the proportions of time exposed to < 0 or > 8 °C were calculated. RESULTS: The temperature remained within the appropriate range in the central and provincial storages. However, the vaccines were frequently exposed to > 8 °C in Saravan and < 0 °C in Xayabouly in the district storage. Vaccines were exposed to > 8 °C during the transportation in Saravan and to both > 8 and < 0 °C in Xayabouly. Thus, challenges in managing the cold chain in the district storage and during transportation remain, despite improvements at the provincial storage. A detailed up-to-date nationwide analysis of the current situation of the cold chain is warranted to identify the most appropriate intervention to tackle the remaining challenges.

Association of strategic management with vaccination in the terms of globalization.

Globalization is having an ever growing impact on the field of vaccine production and distribution in the world and domestically. In this article we examine the impact of taking a strategic approach to vaccination programmes by all the relevant actors: WHO, UNICEF, national immunization programmes, and vaccine manufacturers and distributors. The review of the relevant literature indicates that there are commonalities to the worldwide vaccination programmes. A comparative analysis of various vaccination strategies recommended by WHO and the immunization calendars of certain European countriesis made as well as an analysis of the Serbian vaccination programme. New and more expensive vaccines will continue to appear on the market in increasingly short periods of time.

Drivers and barriers in the consistency approach for vaccine batch release testing: Report of an international workshop.

Safety and potency assessment for batch release testing of established vaccines still relies partly on animal tests. An important avenue to move to batch release without animal testing is the consistency approach. This approach is based on thorough characterization of the vaccine, and the principle that the quality of subsequent batches is the consequence of the application of consistent production of batches monitored by a GMP quality system. Efforts to implement the consistency approach are supported by several drivers from industry, government, and research, but there are also several barriers that must be overcome. A workshop entitled "Consistency Approach, Drivers and Barriers" was organized, which aimed to discuss and identify drivers and barriers for the implementation of the 3Rs in the consistency approach from three different perspectives/domains (industry, regulatory and science frameworks). The workshop contributed to a better understanding of these drivers and barriers and resulted in recommendations to improve the overall regulatory processes for the consistency approach. With this report, we summarise the outcome of this workshop and intend to offer a constructive contribution to the international discussion on regulatory acceptance of the consistency approach.

A Comparative Study on the Lot Release Systems for Vaccines as of 2016.

Many countries have already established their own vaccine lot release system that is designed for each country's situation: while the World Health Organization promotes for the convergence of these regulatory systems so that vaccines of assured quality are provided globally. We conducted a questionnaire-based investigation of the lot release systems for vaccines in 7 countries and 2 regions. We found that a review of the summary protocol by the National Regulatory Authorities was commonly applied for the independent lot release of vaccines, however, we also noted some diversity between countries, especially in regard to the testing policy. Some countries and regions, including Japan, regularly tested every lot of vaccines, whereas the frequency of these tests was reduced in other countries and regions as determined based on the risk assessment of these products. Test items selected for the lot release varied among the countries or regions investigated, although there was a tendency to prioritize the potency tests. An understanding of the lot release policy may contribute to improving and harmonizing the lot release system globally in the future.

Contributions and challenges for worldwide vaccine safety: The Global Advisory Committee on Vaccine Safety at 15 years.

In 1999, the Global Advisory Committee on Vaccine Safety (GACVS) was established by the World Health Organization (WHO) to provide independent scientific advice on issues relating to the safety of vaccines and immunization. Fifteen years onward, we conducted a multi-faceted review to evaluate the impact, reach and challenges facing GACVS, including the role GACVS plays in informing global, regional and WHO member state vaccine policy. The methods included measures of organizational structure, citation impact, themes approached, and a discussion by previous and current members to evaluate past, present and future challenges. Given the increasing range of data sources and the deployment of many new vaccines, the Committee is facing the complex task of identifying the best available evidence for recommendations on vaccine safety. To help meet the increased demand for public transparency in decision making, GACVS-structured methodology for evidence-based decisions is evolving. GACVS also promotes best practices and capacity building for timely and accurate risk assessment; risk communications; outreach to help countries maintain and, if needed, rebuild public trust in vaccines; and advocacy for bridging the major gaps in vaccine safety capacity globally.

Strategic Planning in Population Health and Public Health Practice: A Call to Action for Higher Education.

POLICY POINTS: Scarce resources, especially in population health and public health practice, underlie the importance of strategic planning. Public health agencies' current planning and priority setting efforts are often narrow, at times opaque, and focused on single metrics such as cost-effectiveness. As demonstrated by SMART Vaccines, a decision support software system developed by the Institute of Medicine and the National Academy of Engineering, new approaches to strategic planning allow the formal incorporation of multiple stakeholder views and multicriteria decision making that surpass even those sophisticated cost-effectiveness analyses widely recommended and used for public health planning. Institutions of higher education can and should respond by building on modern strategic planning tools as they teach their students how to improve population health and public health practice. CONTEXT: Strategic planning in population health and public health practice often uses single indicators of success or, when using multiple indicators, provides no mechanism for coherently combining the assessments. Cost-effectiveness analysis, the most complex strategic planning tool commonly applied in public health, uses only a single metric to evaluate programmatic choices, even though other factors often influence actual decisions. METHODS: Our work employed a multicriteria systems analysis approach--specifically, multiattribute utility theory--to assist in strategic planning and priority setting in a particular area of health care (vaccines), thereby moving beyond the traditional cost-effectiveness analysis approach. FINDINGS: (1) Multicriteria systems analysis provides more flexibility, transparency, and clarity in decision support for public health issues compared with cost-effectiveness analysis. (2) More sophisticated systems-level analyses will become increasingly important to public health as disease burdens increase and the resources to deal with them become scarcer. CONCLUSIONS: The teaching of strategic planning in public health must be expanded in order to fill a void in the profession's planning capabilities. Public health training should actively incorporate model building, promote the interactive use of software tools, and explore planning approaches that transcend restrictive assumptions of cost-effectiveness analysis. The Strategic Multi-Attribute Ranking Tool for Vaccines (SMART Vaccines), which was recently developed by the Institute of Medicine and the National Academy of Engineering to help prioritize new vaccine development, is a working example of systems analysis as a basis for decision support.