Key adoption challenges
There are still many challenges as FDA promotes the concepts of QbD. Industry, academia, and FDA need to work together to
pursue the opportunities, overcome the challenges, and realize the benefits that QbD implementation has to offer. This is
necessary to ensure that QbD concepts are incorporated not only when the first activities are initiated around a product's
development, but also during the design of the process that is used to make the product and other activities associated with
a product's life cycle. In conducting its research, the team discovered 10 key challenges related to QbD adoption.
The first four, noted below, are challenges industry faces internally as it attempts to implement QbD:
1. Internal misalignment. One of the most important factors in successful implementation is the application of QbD across the entire operating model.
The research, however, showed that several companies experienced misalignment horizontally across the organization, a disconnect
between leadership and middle management, a culture of conservatism, an unwillingness to redesign certain aspects of their
operating model, and the belief that QbD was low on the company's priority list because the initiative was not required and
the benefits were not guaranteed.
2. Lack of belief in a business case. The majority of companies believed that QbD has a strong business case, but skeptics felt that QbD would slow time to file
(generic products) or that the amount of clinical trials necessary to implement QbD for drug substance production steps (e.g.,
upstream) made the business case negative until there were further advances in the actual science (biologic products).
3. Lack of technology to execute. Specific challenges that were identified included the belief that QbD was an insufficient solution for controlling variability
of raw materials, it would require companies to develop new skill sets and obtain new technology that are viewed as out of
reach, and it would be difficult to gather, manage, and analyze all of the product data generated during development.
4. Alignment with third parties. Industry was concerned about how to bring QbD to fruition while managing a complex supply chain that includes both suppliers
and contract manufacturers.
Based on interviews with industry, six challenges to QbD implementation specific to FDA and other regulatory bodies emerged.
These include:
5. Inconsistent treatment of QbD across FDA. Companies felt that FDA understood QbD requirements differently both within and between offices. This inconsistency leads
to the belief that FDA may not review filings in a consistent manner.
6. Lack of tangible guidance for industry. The majority of companies, especially those in the novice and pilot categories, felt the need for a more tangible guidance
on how to actually implement QbD. Companies wanted clarification from FDA on matters such as acceptable methods, criteria
to select and deselect critical quality attributes, standards by which to judge adequacy of controls, and criteria for analytical
method substitution.
7. Regulators not prepared to handle QbD applications. While FDA continues to take steps to remedy this, interviewees were still concerned about matters such as new reviewers' level
of experience and a perceived high turnover rate.
8. The way promised regulatory benefits are currently being shared does not inspire confidence. This challenge is primarily the result of the lack of codification of real regulatory benefits from FDA. Without clear benefits,
proponents of QbD in industry have expressed difficulty in promoting the idea within their companies.
9. Misalignment of international regulatory bodies. A concern consistently raised by companies at the rollout and fully implemented levels of adoption was whether QbD applications
would be accepted by other regulatory bodies. Although no interviewees had experienced rejection by these groups, they did
comment on the increased time and effort required in other markets.
Table II: Key challenges according to industry segment.
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10. Current interaction with companies is not conducive to QbD. Companies felt that, historically, there was not a lot of comfort talking with FDA; however, companies are eager to open
and improve on this communication.
Table III: Different challenges highlighted by different stages of adoption.
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Table II provides an analysis of what challenges are most relevant for the different drug types, while Table III identifies
what challenges are most apparent by stage of adoption.
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