The UK's Business Continuity Institute defines business continuity management as a holistic management process that identifies
potential effects that threaten an organization, and provides a framework for building resilience and the capability for an
effective response that safeguards the interests of its key stakeholders, reputation, brand, and value-creating activities."5 A number of guidance documents—including NFPA1600 (US and Canada), BS25999 and FSA (UK), and HB221/APS 232 (Australia)—describe
a process and framework for creating and implementing a BC plan.
These plans are divided into three phases: business impact analysis, risk assessment, and final analysis. In each phase, they
focus on three fundamental parameters that are central to establishing business continuity: maximum tolerable disruption period
(MTDP), recovery-time objective (RTO), and process resilience.
MTDP measures the maximum allowable time a business could tolerate an interruption in operation for each key work center or
operation as it pertains to the business's product. Understanding the interdependencies among operations is essential to determine
the MTDP. Identifying the MTDP for technology transfer, manu-facturing, regulatory, and supply-chain processes would be central
to pandemic preparedness.
The RTO sets the metrics for responding to the disruption. An organization must define early in the process whether survival
of the business is the base acceptance criterion for the continuity activity or, in the case of a pandemic response, for countering
the fluctuating demands of the out-break. Having a clear definition, based on recent or forecast data as they pertain to a
pandemic's impact on operations, is essential to defining realistic RTOs.
Resilience describes a process's ability to continue, even in failure. Redundant array of independent disks (RAID) tolerance
for an information technology (IT) network is an example of machine resilience. A redundant power stream is an example of
site resilience. Organizational responsibility distributed by location is an example of organizational resilience.6
Analyzing an organization against these criteria forms the basis for creating an effective BC plan. Figure 1 shows the many
considerations associated with an effective BC plan.
Figure 1. Considerations associated with a business continuity plan
Although such a plan represents a significant undertaking when focused solely on maximizing key stakeholder value, the effort
required and the far-reaching consequences of a poorly developed and poorly executed plan take on a new level of significance
when framed in the context of the inability to respond to a pandemic outbreak.
Technical and Regulatory Hurdles
A key challenge in preparing an effective vaccine is the issue of developing and stockpiling material in advance. Given the
antigenic-shift potential of the influenza A virus, rapid vaccine development soon after the outbreak would probably be critical.
Conventional manufacturing processes, which introduce a virus into millions of embryonated chicken eggs, require at least
six months for producing an effective vaccine (Figure 2).
Figure 2. A conventional vaccine production process requires at least six months for producing an effective vaccine.
Current suppliers of inactivated virus vaccines include Sanofi Pasteur, Novartis, and GlaxoSmithKline. Live virus vaccines
introduce a weakened form of the influenza virus to trigger an immune response by the body. A live attenuated virus vaccine
manufactured by MedImmune has been recently approved.
The best way around technology hurdles is the pursuit of vaccines that use cell-culture and recombinant manufacturing techniques.
Cell-culture processes, similar to those used by monoclonal antibodies manufacturers for decades, could facilitate on-demand
production. Solvay has successfully launched a vaccine in Europe based on the Madin-Darby canine kidney (MDCK) cell culture.
Novartis has a program in Phase-3 clinical trials using the same cell-culture approach. An effective business continuity plan
would require shared capacity among corporations to meet the forecast demand. Currently, the largest cell-culture capacity
is held by the 10 largest biotech giants. These companies must be integrated if the plan is to be successful. To serve the
public's needs in a pandemic, a vaccine would probably have to be manufactured at multiple sites of different corporations.
For this scenario to succeed, the details of intellectual property, cost, and revenue models for the shared response among
multiple suppliers must be negotiated in advance.
The Product Transfer Roadmap
Regardless of whether the pandemic response is to shift operations to another site or to another company, the challenges associated
with scale-up and production optimization would remain. As with any technology transfer and scale-up exercise, a detailed
plan would be required to execute the program successfully. The milestones for the exercise must be driven by the BC plan.
A key element in the plan should involve determining the operational interdependencies that must be migrated to meet the MDTP.
Unlike in the past decades, the biopharmaceutical industry has now embraced operational excellence tools, such as Lean Manufacturing
and Six Sigma, as part of its business model. Leveraging these tools could greatly facilitate the creation of an efficient
BC roadmap that would be effective in a pandemic. Leveraging Lean Manufacturing tools—in particular, establishing the value-stream
map (VSM) for the vaccine manufacturing process as part of the BC plan establishment exercise—would facilitate identification
of bottlenecks and of sources of variation in the process. Complementing the overall business VSM with detailed technical
VSMs would ensure that the BC plan reflected the realities of technology transfer and new drug introduction.
Regulatory agencies have already put processes in place for accelerated approval. In the United States, the Center for Biologics
Evaluation and Research (CBER) has issued guidelines encouraging vaccine manufacturers to explore cell-culture and recombinant
techniques, and to incorporate biological integrators, such as immune response, into their product-development designs.7 If clinical efficacy using accelerated data can be corroborated by surrogate markets, then the development time for the products
may be reduced. In addition, when approval is sought for a vaccine against a pandemic outbreak, and that vaccine is based
on one used for seasonal immunization, the review process is expedited. Regulatory complexity increases, however, if the manufacturer
of the pandemic vaccine is not the same as that for the seasonal vaccine, as would be the case in a shared manufacturing capacity