Laura Bush
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In October 2005, the US Food and Drug Administration and AAPS co-sponsored a workshop on pharmaceutical quality assessments.
The theme of the conference was to establish a path for drug manufacturers to demonstrate sufficient process understanding
in their marketing authorization applications such that future process changes could be made without prior authorization from
regulators. The scope of what the company could do without filing would be set out in a "regulatory agreement" between the
company and the FDA.
This concept of "regulatory relief" was not completely new at that time, of course. Two years earlier, the agency had proposed
comparability protocols as a mechanism for downgrading the level of regulatory filing required for certain process changes.
Through this mechanism, for example, a change that formerly required a "prior approval supplement" would be downgraded to
a "changes being effected in 30 days" (CBE-30) filing, allowing a company to proceed if the FDA did not object within 30 days
of receiving the company's notification of its planned changes.
That concept never took off, however, presumably because preparing a comparability protocol often demanded almost as much
work as the filing it was meant to simplify. As a result, it evolved into the "expanded change protocol" through which one
filing would cover multiple changes, within a defined scope. That idea is getting more traction today.
From the beginning, of course, Quality by Design (QbD) has embraced the notion that companies could make certain process changes
without regulatory oversight; in fact, it's included in the very definition of design space. Somewhere along the way, however, the incentive of companies' gaining regulatory relief in exchange for demonstrating process
understanding was reduced from a major talking point to a quiet murmur.
Instead, many companies now say that QbD is worthwhile even without the incentive of regulatory relief. Some have cited the
increased dialogue among departments that QbD studies encourage. Others point out that design of experiments and multivariate
data analysis will save money by reducing the number of out-of-specification test results, investigations, and lost batches.
Those benefits may be reason enough to embrace QbD. Yet the idea of regulatory relief need not go away, and indeed, it has
not. In this issue (p. 43), a PhRMA QbD working group voices its support for making CMC postapproval management plans—akin
to the "regulatory agreements" discussed in 2005—a reality:
"We believe that continued discussions about the utility of a CMC postapproval management plan will encourage innovation,
and require less burdensome regulatory reporting while maintaining product safety and efficacy."
In other words, they are saying, "let's move forward with this."
I don't fault the regulators for taking the time to carefully evaluate the concept of regulatory relief before implementing
it. Given their responsibility for protecting public safety, caution makes sense. And certainly, there are many companies
who will never merit reduced regulatory oversight. The industry's most scientifically advanced members, however, have demonstrated
a level of process knowledge that warrants granting them some freedom to implement continuous improvement.
In short, regulatory relief is a concept whose time has come.
Laura Bush is the editor in chief of BioPharm International, lbush@advanstar.com
