As a regulatory process, when submissions for new or abbreviated drugs are provided to global health authorities (HAs), it is a standard expectation that HAs will issue questions that delay the approval timelines until clarifications can be provided. Pharma companies traditionally look to provide the right balance of insight and clarity to ensure HAs can provide approvals of new drugs, but the questions can create long-standing efforts and slow the process. The Regulatory Affairs Digital Strategy Council, sponsored by Indegene, conducted an industry-wide survey across 15 pharmaceutical companies on the insights of Health Authority Questions / Queries. The Council Survey provided insights into the reason for these challenges, actions taken to improve the process, and data leveraged through digital approaches.
At the Indegene Digital Summit 2022, industry experts from Alexion, AstraZeneca, and Intercept Pharma discussed the survey results and shared their insights on past experiences and approaches to ensure approval with HAs. Panelists shared the best practices to reduce these HA questions that delay approvals. They also talked about digital approaches that provide value and insights in a scaled pharma company.
US FDA and EMA, as you might have expected, issue many questions. Much scrutinization is provided to ensure a high level of clarity on what has been submitted, such as an understanding of the clinical backdrop, details of the manufacturing process, etc. There are certain areas of submission that receive questions more commonly from HAs -
Read the industry survey in detail here
Good submissions do not guarantee that one will not receive questions from HAs. Questions do come up, and it does create some delays. Paul Nitschmann SVP, Regulatory Affairs at Intercept pharmaceutical, says, “Questions are here and are here to stay. Because we give packages that are as complete as we believe regulatory authorities need to make decisions. And that does not necessarily mean that we give them everything we have or know.” Martine Zimmermann, SVP, Regulatory Affairs & Quality at Alexion, emphasized the need to anticipate questions and readiness to answer. There are three buckets of questions, (1) Questions we were anticipating and need a little bit more time to prepare for them, (2) Administrative questions, and (3) Clever questions that show HA may have seen similar information from other sponsors.
Certain areas of submission receive questions more commonly from HAs, and panelists are not surprised by this. For example, many organizations try to find the right balance while sharing manufacturing details with the regulatory authorities, as there can be much proprietary information. No one would want to share everything. And this triggers many HA queries. Since clinical studies, their results, and the proposed labeling information are way more open to interpretation, more questions are asked, and regulators often give them a unique twist that requires additional thought and tweaking of the prepared responses. But the numbers of validation questions received for some of these sections are extremely low, which is good.
Anticipate questions and be ready for them to improve the process. Since the time to submit is limited, one can prepare only so much for the actual dossier. One must move forward and prepare for those anticipated questions at the back end. But there are more ways to improve the process further. Michael O'Flynn, Executive Director Regulatory Affairs Management & Digital Strategy at AstraZeneca recommends looking for trends by analyzing the questions that are consistently received on applications. Proactively applying those insights to submissions might help receive fewer queries
“Ability to utilize responses to questions across health authorities is an opportunity” - an opportunity to recycle and reuse information - Michael O'Flynn
Another approach is to access the data bank of questions received across projects and analyze them. Digital interventions present much scope for process improvement here as they can help avoid the churn in the visibility over past queries and responses.
“The extent of information you put in the system will be of paramount importance” - Martine Zimmermann
ROI calculation is a challenge with digital adoption. With contributions from multiple functions and different time-recording practices, it takes a lot of work to capture the actual cost of responding. The time recording practice in many companies is at the project level, which is not granular enough.
Paul Nitschmann shares the current scenario before putting forward the possibilities with digital adoption, “Many companies have built a database of questions/queries asked, and the searching process is largely manual. But this manual search carries a risk of missing important information. So, there is much value to be realized with digital solutions that can provide a systematic machine capturing and processing of HA queries and responses. Trend identification and insights generation from the digitized database can assist in authoring responses. It can bring anticipation of questions, structured content authoring, consistency in responses to different HAs, and across one’s entire portfolio to individual HAs.”
“Developing a database of HA queries and searching through it is largely manual today which carries a risk of missing the important information” - Paul Nitschmann
“Ability to consolidate, interrogate and catalog information received in unstructured, semi-structured form through varied documents is going to be the key,” says Michael O'Flynn. From there, one needs to work towards developing predictive analytics that will auto-suggest answers to questions.
Overall, this panel discussion is filled with examples from the day-to-day practices of industry experts, and also the aspirations with the digital transformation that can assist in getting to YES sooner. The insights help in identifying potential areas of HA Query management deserving transformation and how digital initiatives can make the best use of HA queries as intelligence to accelerate regulatory approval.