While the the US Food and Drug Administration (FDA) has stressed Quality-by-Design (QbD) applicants will enjoy regulatory flexibility a survey shows some people are still wary. BioProcess Technology Consultants (BPTC), which ran the survey, pins the confusion on FDA reviewers.
“The confusion seems to stem from the mixed responses people have gotten from regulators. Stories I have heard indicate that understanding of QbD by FDA reviewers is variable,” Sheila Magil, senior consultant at BPTC, told in-PharmaTechnologist.com.
A focus of the survey was the level of QbD understanding and implementation among biopharma companies but, Magil says, there is also a need for some regulators to increase their knowledge.
“It is important to realise that...the regulators must understand what QbD is, why it is worth it to use a QbD development approach and how to implement the approach,” Magil said.
The situation at regulators mirrors, in some regards, the shortcomings at biopharma companies. Regulators have some people who are well versed in QbD - and are doing a relatively good job of speaking out on the topic - but many feel the level of understanding is unevenly spread.
Companies can increase the breadth of understanding by building a team of experienced users who can mentor others on QbD. To get the most from their efforts though companies need FDA reviewers who can respond to their questions, otherwise QbD could actually be burdensome.
Magil used the example of Genentech, a company that has worked with the FDA on QbD but still chose to include all the back-up data, risk assessments and justifications in a submission. “The result of this was that the CMC section was around 1,500 pages,” Magil said.
Examples like the Genentech case possibly explain why 15 per cent of the 20 respondents said fears of regulatory delays are the biggest hindrance to QbD adoption in biologics. The example may also play a role in one-fifth of respondents citing lack of cost efficiency as the main hurdle.
If QbD is working how the FDA envisions neither factor should be a deterrent. The FDA stance was shown in 2010 when Christine Moore - interviewed by in-PharmaTechnologist.com here - said increased product and process understanding can cut manufacturing and regulatory costs.
A greater understanding of QbD on both sides of the industry-regulatory divide will help. There is plenty of room for improvement. Less than one-third of respondents described themselves as ‘very familiar’ with QbD, while one-fifth were either yet to use it or view it as irrelevant.
Support from professional organisations, internal and external training and sending “a more diverse range of people to conferences” will help companies educate staff on QbD, Magil said.