PDUFA meeting airs industry's take on FDA communications
A required review of the US Food and Drug Administration’s communication with industry found that communication was overall timely, collaborative and effective at moving development programs down the road. However, feedback from industry and details of an outside consultant’s report also identified some notable gaps.The consultant-prepared communications assessment presented in an 11 August public meeting fulfilled requirements of the Prescription Drug User Fees Amendments of 2017 (PDUFA VI).
The report, which gathered data from the US Food and Drug Administration (FDA) and included an extensive industry poll, provides a detailed snapshot of communication between sponsors and FDA, with a breakdown of the number of communications and the timeliness of the communication from FDA at each stage of the drug development process.
Overall, investigational new drug (IND) application-related communications are characterized as “clear, effective, efficient, collaborative, and timely.” However, both staff shortages and heavy workloads at the agency presented challenges; moreover, even in pre-pandemic days, teleconferencing was often hobbled by technical challenges and glitches.
Meetings per IND were higher for breakthrough therapies
For example, over the one-year assessment period, sponsors requested a mean of 1.7 meetings per investigational new drug (IND) application, though for breakthrough drugs, that figure rose to 2.7. Of these, sponsors requested meeting dates that fell within FDA guidance just 57% of the time; 54% of the requests contained all required items, and 29% contained all the guidance-recommended items. In 90% of studied cases FDA staff who were knowledgeable in the relevant subject matter areas answered the questions submitted by sponsors.
Almost all the requested meetings were granted, and FDA was able to respond to a meeting request within the guidance-recommended timeframe 82% of the time. If the question and the path for development was also clear, a written response only (WRO) sometimes sufficed.
Most package submissions were timely – but incomplete
Moving along the development path, a mean 1.5 meeting packages were submitted per IND; the figure was 2.5 for breakthrough drug INDs. Of all submissions, 79% were submitted on time, with just over a third (35%) containing all the items FDA recommended in the pertinent guidance.
At this point, FDA issued a mean of 1 preliminary comment per IND (2.5 for breakthrough drugs), with 84% of these responses happening in a timely way. Meetings were cancelled by the sponsor 22% of the time after they received FDA preliminary comments, meaning that the questions were adequately answered without needing a meeting in these cases. About a third of the time, FDA responded by saying that the meeting package submission did not contain enough information for the agency to answer at least one of the questions posed by the sponsor.
About three quarters of the time, preliminary comments from FDA also raised issues that had not been identified by the sponsor, according to the report.
A mean 1.1 meetings (2.0 for breakthrough drugs) were held per IND after package submissions, with a mean of about 20 attendees and about half being held face-to-face. Overall, 83% of the meetings were Type B or C, and 65% addressed clinical topics as well as other topics.
Most post-meeting responses were timely and relevant
Post-meeting, 89% of the minutes or written responses only (WROs) were sent out within the guidance-recommended time frame; the content of the responses was consistent with meeting discussions. However, more than half of the minutes or WROs also addressed topics not included in meeting packages.
For each IND, FDA sent a mean 4.4 information requests to sponsors, and sponsors submitted a mean 14.3 amendments to FDA.
Takeaways:
From the agency perspective, sponsors who have substantive questions should submit meeting requests rather than sending the questions via email or asking a regulatory project manager (RPM) for the answer in a phone call, according to the report.
However, sponsors perceived RPMs as being responsive and hard-working, with an email or phone call often the best way to get an update or an answer to an uncomplicated question. The report found that though agency staffing might shift during the course of an IND, these shifts didn’t result in unexpected changes in advice or upset to the development programs.
Sponsors see strengths – and opportunities to improve
Industry’s responses to an independent assessment of the agency’s communications pointed out areas where there was perceived room for improvement.
Eric Larson, senior manager for regulatory affairs in the global regulatory strategy department at AbbVie, provided some industry perspective during the meeting. Larson affirmed that accurate, clear and timely communication from regulators is key to advancing products through the IND process. Communication from FDA, he said, usually meets those standards: “My own experience, and that of most of my colleagues, has been extremely positive working with regulatory project managers.”
Regarding the frequency with which sponsors request meetings that are out of PDUFA timelines, Larson said that some requests may be offered “as a courtesy” to busy FDA staff who are struggling with workloads.
“It has sometimes been striking to note the differences in communication practices between [FDA] divisions,” said Larson. These differences can range from allowing slide presentations during meetings to preferences for postal service communications or email exchanges.
Particularly during the pandemic, said Larson, email should be the preferred means of communication. He cited one instance where a center used “snail mail” as the only source of outgoing communication, which resulted in “considerable issues” during the IND process. Even minor delays, he said, can result in compounded logistical challenges down the road for the sponsor.
Regarding virtual FDA-sponsor meetings, Larson offered some best practices and lessons learned during the COVID-19 public health emergency. An on-time start is key, he said, and the line should remain open. Abbvie, he said, has attended virtual meetings where the FDA team has gone on mute for extended periods, leaving the sponsor team uncertain about whether the call is even continuing. Operational and technical logistics should certainly be nailed down before a virtual meeting, he said.
E. Cartier Esham, PhD, senior vice president of science and regulatory and executive vice president of emerging companies at the Biotechnology Innovation Organization (BIO), also shared industry perspective. “We would like to work together to establish a mechanism for sponsors to obtain questions to clarifying questions following milestone meetings,” said Esham. The goal would be to avoid additional meetings and avert the potential for miscommunication and consequent delays in development.
Esham also noted that she appreciated the variety of sizes and types of industry organizations that participated in the review. “The gene therapy pipeline is growing with extraordinary speed,” she noted, so paying close attention to communications processes at the Center for Biologics Research and Evaluation (CBER) will be key in upcoming months and years. Another focus in the time of rapidly evolving therapies, she said, should be early and effective communication with first-time submitters during the pre-IND phase. Allowing in-person pre-IND meetings when requested would go far to support first-time sponsors and those with novel products, said Esham.
Rather than limiting the number and scope of sponsor questions for a meeting, said Esham, industry and FDA should work together “to ensure meetings accomplish their purpose.”
FDA report