Understanding the portfolio demand over time
The shifting product mix for building B633, including products aimed at large patient populations, high doses, and chronic
indications, to a blend of high and low clinical and commercial demand, necessitated an overall evaluation of MedImmune's
assets within its manufacturing network. Because B636 was configured to lower product requirements, appropriate product candidates
had to be shifted from the B633 facility to another facility, or initially manufactured in that facility in the future. B636
contains shell space suitable for installation of additional upstream and downstream manufacturing capabilities. The company
is therefore evaluating the use of disposable technology to fit out this shell space, thus offering greater flexibility in
terms of rapid installation of required capacity to meet ever-changing product demand.
Although the industry has been slow to adopt disposable technology, recent advances in consistency of manufacturing, increased
reliability of equipment, and expanded use in early-phase clinical manufacturing makes the use of disposables a viable alternate
to fixed stainless steel bioreactors.
Outsourcing is another option for meeting clinical product demand without major capital investment for facility modifications.
Most products in the development portfolio at MedImmune are antibody-based and expressed using mammalian cell culture. As
a result, the manufacturing process is generally consistent from product to product and well suited for FMC. But if a product
that is expressed in a microbial based system or that has low clinical/commercial demand is introduced to the facility, then
the nature of the process will necessitate significant capital investment into the facility to manufacture the product at
commercial scale. The production process for that product may require additional steps that do not fit within the facility's
current design. Such a change requires reassessing the plant's fit. What modifications are needed to make the new clinical
process fit within the facility? Is this a cost-effective investment for the company?
To answer that question, a company also needs to look at the future demand for the product, stage of clinical manufacture
and projected capacity utilization if the product is successful. Let's say, for example, a facility has the capacity to produce
80 batches of product a year, and a new product candidate requires only two batches a year to service the commercial market,
yet a capital investment of $15 million is required to alter the facility for process fit. In this case, outsourcing at a
minimum clinical supply may be a better option until further certainty of success for the product is understood.
Ensuring future product candidate processes are efficiently transferred
Because the FMC facility services both internal and external partners for the scale-up and manufacture of late-phase clinical
and commercial supply, the company had to establish and maintain a common approach to technology transfer, build knowledge
and understanding of the facility constraints with all stakeholders, and drive towards platform technologies. The key was
bringing everyone into the development process at the earliest stage. With this approach, FMC management was able to provide
feedback on direction and impact to the site.
In addition, all stakeholders needed to be instructed on the capability and operating aspects of FMC so that they could develop
standardized models (i.e., columns size, flow rates, buffer amounts) and ensure that their processes worked within the boundaries
of the existing facility. Today, the company is creating a better working relationship between process development and the
manufacturing organization; they are sharing knowledge and information, and building back that data into the established parameters.
The goal is to create processes that seamlessly fit FMC rather than making costly capital investments that may risk the product
timeline.
FMC is still in a state of transition. For some products, MedImmune is receiving late-stage clinical material with processes
designed years before the facility was commissioned in 2010. In some cases, the team may have to adapt the facility slightly
to meet the process. Overall, putting together a facility-fit analysis earlier in the lifecycle of the process ensures that
it is ready for the facility, and allows for a more seamless flow from late-stage clinical to validation and commercialization.
GREG LIPOSKY is general manager/vice-president of the Frederick Manufacturing Site at MedImmune.
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