Process analytical technologies
BioPharm: Along these lines, have you witnessed more interest in process analytical technologies (PAT) from sponsor companies? Has
your company applied PAT to date or does it plan to?
Kauffman (Lancaster Labs): Lancaster Laboratories has witnessed interest from sponsors and contract manufacturing organizations (CMOs) in using PAT
for biopharmaceutical production. Quality-by-design (QbD) processes are used in bioreactors, for example. Although rapid sterility
and mycoplasma testing approaches are coming to fruition, the technology is not here at this time to measure other important
parameters such as post-translational modifications or adventitious viral agents in real time.
Breau (MPI): Not yet. The presumed future increase in the need for PAT services will be driven as FDA's QbD initiative evolves. We have
not seen a dramatic increase in the request to characterize raw materials or other process components.
Platform approaches
BioPharm: What is your take on platform technologies to develop and test biopharmaceutical products? Can you offer a CRO's perspective
on the pros and cons of such an approach?
Gillett (Charles River): In many ways, platform technologies are both beneficial and essential in the CRO setting to enhance productivity. Processes
ranging from immunoassay development to telemetered data collection are constantly improved to increase efficiency. These
efficiencies evolve into beta testing and standard operating procedures (SOPs). For example, Charles River recently pushed
its reporting timelines to a new standard through platform technologies.
Sponsors could save cost and gain efficiency if one set of 'platform; toxicology data could support multiple products (e.g.,
a number of agents based on similar chemistry). But implementing this concept is more difficult than it sounds because small
chemistry changes can make profound changes in drug distribution and drug effects. Consequently, regulators have been cautious
about accepting platform data and generally require individual toxicology programs for each drug substance. We may see a shift
in regulatory approach as FDA's modernization program gains momentum and as more data accrues on novel agents, such as gene
therapy vectors, or on classes such as biosimilar monoclonals.
Kauffman (Lancaster Labs): There are definitely benefits in the platform technology approach. If a process is well understood and can be applied to
produce an array of biopharmaceutical products, then it may, for example, be possible for the sponsor to reduce the amount
of viral clearance testing performed on all products manufactured using the same processing platform. Transfer and validation
of methods also can be expedited and streamlined. However, one size does not fit all, and it is not always easy to predict
when a platform technology will apply. A small change in a process or product may go undetected in a platform method, and
this could end up taking more time on the back end to redevelop and validate methods.
Breau (MPI): Novel platform technologies are developed because, presumably, they confer some advantage in certain applications over the
alternative competing platforms. MPI conducts a return-on-investment (ROI) analysis to assess whether we should invest in
the platform. We are careful in assuring that a thorough assessment is completed before an investment is made.
Sponsors must be aware that moving forward with a cutting-edge platform that could fail or be removed from the marketplace
may cause significant rework and delays in development plans. The sustainability of a new platform must be taken into account,
as well as the novel advantages that it may confer.
Reason (SGS): Platform analytical technologies, at certain levels are appropriate and can be applied to a wide range of products. However,
the more advanced methodologies have to be tailored to suit specific circumstances, particularly with wide variations in formulations,
and so forth.
For example, platform technologies can be applied to all IgG1 mAb products, which are similar structurally, but the methods
used to purify these products prior to analysis will vary depending on the product formulation. Other glycoprotein products,
such as Erythropoietin and FSH, require more in-depth analysis particularly of their glycosylation. This analysis may require
further development of methods to be able to characterize the glycans at each of the glycosylation sites within these products.
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