16 minute read
Start with Y A case for better pandemic preparedness
START WITH Y
A case for better pandemic preparedness
In both an Australian and a global context, there is a pressing need to consider a rebalance and increased investment in preparedness planning for pandemics and other significant national emergencies, rather than the current heavy focus on response and recovery.
Leigh Farrell, Lead, Health Security Systems Australia (HSSA)
While COVID-19 is not yet behind us, there has never been a better time to consider the meaning of national resilience and to prepare for the next threat.
It’s almost universally agreed—in respect of pandemic preparedness—that there will be a . Monkeypox, while not a pandemic, has been formally proscribed as a public health emergency by the World Health Organization (WHO). If COVID has been the wake-up call the world needed to shatter its complacency about a so-called Disease X, then how are we ensuring that we’ll be better prepared for Disease Y?
Working in the defence and national security sector exposes you to a lot of jargon. The military is infamous for its acronyms and often accused of having a language all of its own.
One of those terms that I’ve taken to heart is the idea of system-of-systems challenges. These are wickedly complex scenarios for which a truly comprehensive view of capability development is needed. The Australian Defence Force describes this with terms like fundamental inputs to capability, a recognition that an enormous range of enablers and other factors must be considered—and are
There is a compelling and urgent need to rethink, and rebalance, our approach to preparedness planning for pandemic threats and other man-made or naturally occurring disasters, writes Leigh Farrell.
critical to success to deliver an effect such as pandemic preparedness—in addition to the acquired commercial ‘product’ or equipment solution.
It’s no surprise that these wickedly complex problems such as global pandemics require system-of-systems solutions, but this is where we see cracks starting to appear in relation to resilience and disaster response. While we see innovative work on elements of those systems, there is too often a lack of situational awareness of one system as it relates to another system. Planning in one system is developed often independently from that in other another system. One example might be assumptions made about the capacity and capability of Defence to contribute to hazard management or humanitarian assistance missions, from the point of view of civilian first responder agencies. Another might be data collected in one system or agency that is not shared (either in time or at all) with other nodes of the system.
In the solutions space, key players across the sector (governments, industry and researchers) need to come together to create collective early warning systems that take account of multiple inputs— disease surveillance, epidemiological testing, open source intelligence and industry capability analysis among them—rather than focusing on any one dimension of the solution.
There is also more work needed on the macro health security implications and macro-economic cost considerations of national response planning. Creating pull factors for innovation is one example. Australia is very good at some elements of innovation, but not so much, I would contend, in innovative policies around agile procurement and policy settings. Where supply chain vulnerabilities are evident, the steps to remedy those are slow and an appetite for transformational ideas is wanting. The potential to implement and fully leverage public-private partnerships, similar to Operation Warp Speed in the US, is yet to be fully explored. Special economic zones are another example of a transformative idea with big potential to drive innovation and build sustainable industry capacity.
Coordination across state and federal jurisdictions and with the industrial sector is occurring and some agility is evident, so to look in the rear vision mirror and say “everything we’ve done before was rubbish” would be simplistic at best. We should acknowledge those elements of the system, the muscle that has been exercised and is building nicely, while also committing to doing better in other areas.
In thinking about the prevention and preparedness elements of the Prevention, Preparation, Response, Recovery (PPRR) risk weighted model, it’s hard not to conclude that more balanced investment is needed. Australia’s Productivity Commission has reported that 97 per cent of funding allocated for natural disasters is spent in the response and recovery phases, and only 3 per cent in the preparedness and prevention phases.
In assessing the gaps in PPRR planning for particular threats, it is clear that a multi-faceted approach is required to align our PPRR plans with global best practice. Investment also has to be balanced in respect of not putting all of our eggs in one basket. It was already known, but is now even clearer from global experience, that the world could not simply vaccinate our way out of the pandemic. Of course, vaccines and therapeutics are important tools for managing infectious diseases and pandemics but it’s important that we use all the tools at our disposal and develop system-of-systems approaches. This includes considerations like PPE, modelling and simulation, decision support tools, medical devices and surveillance.
We are also learning hard lessons about the fallacy of the ‘one bug, one drug’ mindset. Focused attention and priority needs to be given to the development of platform technologies and developing broad-acting, threat-agnostic countermeasures against families of bacterial and viral pathogens. In seeking to catalyse research and development activities, further attention is needed to setting more precise strategic requirements rather
than more general guidance on areas of interest.
With COVID-19 we saw innovation in the regulatory system where master protocols were adopted for clinical trials, for example, and this allowed a pooling of the data globally, in turn leading to more rapid approval for these vaccines. Anticipatory work on master protocols and streamlined emergency use authorisations is one area where an investment in preparedness and prevention could reap substantial dividends.
We need more sophisticated simulation, modelling and decision support tools – as well as advanced measurement technologies and access to expertise in foresighting – to understand what we are dealing with, on a domestic and international scale. Recovery and response strategies need to be comprehensively stress-tested in both desktop and field exercises involving all relevant responding agencies.
As part of its CBR Sensing System Program, the Health Security Systems Australia (HSSA) division of Australia’s DMTC Limited is investing in projects focused on the development of sensing technologies that alert the wearer to chemical and biological threats, allowing more time for interventions such as medical countermeasures, and supporting rapid operational decision making. We are also working on hazard-prediction models that could provide time-critical information to decision-makers. Fasterthan-real-time urban wind and plume transport models hold the potential to revolutionise atmospheric transport and dispersion modelling and simulation tools that are used to predict the spread of airborne hazards in urban environments.
In our own backyard, surveys have consistently shown that Australia’s medical technology and health innovation system has A-class components but, by comparison, only C-class connectors and wiring. These judgements are useful inputs to discussions about priorities and actions that can be taken to address gaps in both capacity and capability. Surveys, however, are only limited in their scope and value. They are static snapshots and what is needed, in their place, is a dynamic and evolving picture of the landscape.
Working with stakeholders across the Australian Government, my division is taking important first steps towards this envisioned outcome for Australia by developing a national health security database. With unknown but anticipated threats ahead of us, a database like this will identify health security sector capability and supply chain resilience, which will inform both policy development and targeted investment.
To draw on another bit of Defence jargon that I think is most relevant here, the Australian Army often talks about the challenge of being “ready now and future ready”. Lashing these two horizons together is an acknowledgement of a dynamic and constantly evolving threat landscape, and the need for a balanced view when it comes to priority setting, investment decisions and policy frameworks. Achieving one of the twin aims at the expense of the other is simply not an option. It requires a culture and decision-making mindset that keeps pace with change rather than lagging behind it.
Conclusion
Whether for natural disasters or pandemics, experts agree that there is little time to sit and ‘admire the problem’. The resources and investment needed to tackle these problems are finite, and contested, which focuses attention on selecting the most relevant research and investing in proposed solutions that show the most potential. The capacity for thinking beyond borders is also sorely needed. Horizon scanning is critical to identify and implement best practice, and to stay ahead of the curve.
References are available at www.pharmafocusasia.com
Leigh Farrell is an experienced senior executive having held senior global roles in the biotech and pharmaceutical industries. He currently Head Health Security Systems Australia (HSSA), a newly-formed division of Australia’s DMTC Limited. HSSA operates within DMTC’s program management structure and focuses on the protection of military and civilian personnel against chemical, biological and radiological threats, and emerging diseases. Its work is built around the success of a Medical Countermeasures program that DMTC has led in Australia, with support from a whole-of-government agency group, since 2016. The division’s work extends beyond medical countermeasures to include other areas such as modelling and simulation, and sensing systems.
AUTHOR BIO
What are the implications for the Life Sciences industry?
Christian Berg, Life Sciences Solutions Architect Consultant, Emerson
In 1998, Genentech received regulatory approval for Herceptin, a monoclonal antibody targeting HER2 positive breast cancer, marking the beginning of the modern personalised healthcare revolution. What made Herceptin different? It was the first adjuvant therapy targeted at a subset of a population that was identified using molecular diagnostics to ensure that only patients who could benefit from the treatment would receive the treatment. Today, use of companion diagnostics and targeted therapies is widespread, and healthcare providers are beginning to leverage molecular residual disease (MRD) diagnostics to adapt and tailor each patient’s treatment in pursuit of curing disease. The personalised healthcare revolution has arrived, and the life sciences industry needs to adapt by accelerating new product introduction and technology transfer for manufacturing facilities, enabling contextualised real-time data capture, and developing integration and operations analysis tools that enable real-time release for GMP products.
The Life Sciences Industry is Rapidly Evolving to Cure Disease
FROM
Diagnostics are regulated as a function of statistical repeatability and reproducibility studies. Treatment protocols are a function of populationbased studies, dependent upon study participant selection using population-based diagnostics. Treatment efficacy is limited by variations within clinical study populations. Manufacturers are incentivized to produce large batches based on population-derived demand forecasts. Therapeutics are centrally produced and distributed globally.
TO
Precision, patient-specific diagnostics are regulated as a function of controlled processes Treatment protocols are a function of precision diagnostic generated bioinformatics leading to patient-specific courses of treatment. Treatment efficacy is not limited to confidence intervals that are constrained by variations within the population; treatment that leads to cure is an expectation for all patients. Manufacturers are incentivized to minimize batch sizes in favor of real-time production. Manufacturing supply chains are flexible, with localized production capabilities to deliver specific therapeutics as close to real-time as possible.
Personalised healthcare is characterised by providing a unique, empirically informed treatment regimen for each patient, based on each individual patient’s expressed disease characteristics and how the patient’s disease responds to treatment.
Personalized Healthcare Overview
Technology Approach Needs to Adapt to Personalized Healthcare Challenges
Patient is grouped with cohort based on traditional diagnostics. Disease profile is isolated using precision molecular bioinformatics to tailor and modify treatment until patient is cured. Treatment is not solely a function of therapeutics; it is a function of patient-specific treatment response as well.
The focus of Emerson Life Sciences is to address digital technology challenges in order to enable the personalised healthcare revolution. These challenges include: 1. Accelerating new product introduction and technology transfer for manufacturing facilities. 2. Driving real-time, end-to-end data capture with query-able context. 3. Enabling real-time release for GMP products.
For the life sciences industry, New Product Introduction (NPI) and Tech Transfer (TT) have been characterised by detailed project management involving collection of process definition information, production line configuration, deployment of process definition information into process controls,
FROM
Isolated databases Digital stack of applications Requests for proposals and supplier-driven deployment Long lead-time for system implementation and integration
TO
Shared OT data core Ecosystem of applications Marketplace purchases and customer-driven deployment Rapid, modular deployment of new functions
and validating that the facility functions as intended with respect to the product being introduced. This leads to resource-intensive and lengthy initiatives that inhibit delivery of novel, high-quality, life-saving treatments at reasonable cost. NPI and TT have both logical and physical requirements that need to be addressed to accelerate the personalised healthcare revolution.
Key to accelerating NPI and TT is having product and process definition information accessible from a single, shared source that spans the product lifecycle from product development to pilot-scale production to commercial production. Once product and process information has been consolidated into a shared platform, that information can be leveraged to determine facility fit and rapidly cascade the relevant process definition data to a receiving plant. Integrating and accelerating logical changeover is dependent upon receiving facilities having implemented local, parameterised control system configurations that align with equipment models shared between the enterprise process definition system and the plant process control system.
With product and process definitions consolidated, and equipment models aligned, one final NPI and TT challenge to overcome is rapid changeover and implementation of new equipment. We typically refer to this concept as ‘plug-n-play.’ Pragmatically, this requires standardisation of control system hardware components, interchangeable controller configuration packets, and electronic marshalling. In response to these challenges, equipment manufacturers have begun partnering with control system suppliers, like Emerson, in order to make ‘plug-n-play’ a reality for life sciences manufacturing.
As detailed product and process definition data gets consolidated into single-sources-of-truth, and physical manufacturing equipment standardises on ‘plug-n-play’ capable controllers, the time and effort to complete New Product Introduction and Tech Transfer will decrease in support of the needs of personalised healthcare manufacturing.
Move Beyond Electronic Batch Records with an OT Data Core
Electronic batch records (eBR) are widely adopted by the life sciences industry to minimise data entry errors, streamline compilation of production records, and enable review by exception to reduce time and effort required for product release. Manufacturing Execution System (MES) is a core enabling technology for eBR, and it works in concert with Enterprise Resource Planning (ERP) and Process Control Systems (PCS) to orchestrate production activities, enforce controls, and capture relevant data. These systems have significantly improved operations management activities related to production records. Implementation of eBR is typically dependent upon complex integration of application suites across the digital landscape which leads to data replication, application-specific interfaces, and limited reporting and analysis capabilities.
Smaller batch sizes, more frequent product changeovers, increased traceability requirements, and shorter product lead times are exposing limitations of the traditional MES-based eBR approach. Implementing an Operations Technology (OT) Data Core as the single source of truth for execution data provides a new information management foundation upon which to build the next generation of process control and production records. The OT Data Core must not only meet regulatory data integrity requirements, it must also be able to facilitate platform-agnostic data sharing with query-able context.
The Data Core needs to be able to support many data types and data sources while providing context-driven storage and accessibility. This technology differs from traditional data historians which are typically dependent upon time, sequence (or series), and source identity (or instrument tag) for organisation and retrieval. OT information needs to be readily accessible by many systems and users with simple yet specific data identification to facilitate retrieval and usage.
To make the most of a Data Core, operations management activities need to be orchestrated by functionally specific applications that conform to Data Core context standards so that data can be published and shared across many users and use cases. A key consideration when developing and documenting manufacturing processes will be to understand which data inputs and outputs are shared across many platforms, use cases, or users. This data set represents the beginning definition of scope for the Data Core contents and informs user requirements for the Data Core. The OT Data Core facilitates pursuit of a ‘single-source of truth’ for execution data. Additionally, aligning functional applications to the Data Core enables flexibility and rapid scalability for the manufacturing digital ecosystem.
Reduce Lead Time with Real-Time Product Release
Addressing the final challenge to agile, patientfocused, manufacturing supply chains requires addressing a primary cause of long product leadtime, product release. GMP product release involves thorough evaluation of production records that include evidence of compliance to approved process standards, quality test results, and deviation investigations and responses, to name a few. Many of these elements are addressed by eBR systems that include Review by Exception (RbE) functionality, but there are components that exist outside of traditional eBR implementations that contribute to lead time and effort.
One of the contributors to extended lead times is resolution of process deviations. Realtime identification, investigation, and resolution of process exceptions can readily be implemented for existing eBR systems with RbE through adoption of exception-handling specific functionality that triggers an immediate response from operations managers and quality assurance when exceptions occur. Addressing deviations in real-time requires a technological component that is connected directly to the manufacturing process to identify the need for quality action and record associated investigation and remediation activities. It also requires a behavioral norm within the manufacturing organisation to immediately respond, investigate, and resolve investigations. Having this real-time deviation response functionality embedded into the eBR system can help drive the desired organisational behaviour.
Another contributor to extended lead times is off-line product quality testing. Spectral Process Analytical Technology (PAT) is a rapidly evolving solution to evaluating product quality as a function of physical properties that can be measured with in-line instrumentation. When integrated with a control loop, PAT can be used to optimise production performance, enforce product quality, and predict deviation conditions before they occur. Process development teams are actively pursuing means to measure and record product quality attributes in-line, and PAT is a promising option in pursuit of real-time quality control.
With process data being digitally captured, contextualised, and evaluated in real-time, implementing a holistic, real-time product release platform is becoming a greater possibility for more life sciences manufacturing organisation.
AUTHOR BIO
Christian has a passion for driving operational excellence and leveraging digital solutions to enable world class performance. He offers over 24 years of life sciences industry experience in automation, engineering, manufacturing, and process and systems transformation. Just prior to joining Emerson, he was Director of Manufacturing for oncology pilot plant operations at Invitae (formerly ArcherDX) where he implemented operations management standards and initiated digital transformation to enable Personalised Cancer Monitoring (PCM) production. Prior to Invitae, Christian held multiple operations management positions at Johnson & Johnson, Genentech, and Amgen.
Meet the Needs of Personalised Healthcare
The personalised healthcare revolution gives us the tools necessary to end treatable disease caused deaths in our lifetime. In order to enable this exciting new approach, our technological focus needs to shift from viewing specific medical devices or therapeutics as the value object of our processes to viewing each patient’s healing as the ultimate value proposition of an integrated process. To do this, industry needs a more sophisticated digital toolset that addresses real-time contextualised data capture, rapid product and process introduction for manufacturing, and real-time release of GMP products.
