My fingers were tired last night so I did not get to capture a highlight of the presentation made by
Dr. Iilun Murphy, Director, Office of Generic Drugs, which is usually one of the biggest draws of this annual conference.  So, let’s take a step back and provide you with some tidbits from her presentation.

First, she did not have a slide with the standard ANDA metrics we all hoped to see, but I thought I heard her say that the FDA received 724 original applications.  I know that the full Fiscal Year (FY) 2024 numbers have not been scrubbed yet, but if that number stands, since the number of ANDAs officially received through August was reported as 600, that means that the OGD must have received 124 new ANDAs in September.  While we predicted a high submission volume for September 2024 (primarily due to the significant increase in the GDUFA fees for FY 2025, which began on October 1, 2024), we did not think that it would be that high.  We still won’t provide final comments on that number until the September official stats are posted on the FDA’s webpage.

In addition, Dr. Murphy provided some comments on estimates of the number of complete response letters, the number of supplements received, as well as some other estimates of 2024 numbers, but again, I would rather wait until the official exact totals are posted on the final 2024 Generic Drugs Program Monthly and Quarterly Activities Report, which will likely appear sometime in late November.

One topic she mentioned repeatedly in her presentation was the need for reliable data. Some examples taken from her presentation include:

“Companies need marketing approval supported by reliable data before beginning manufacturing.

  • FDA regulations require sound, ethical practice.
  • Studies must be conducted in a way that ensures the integrity of the data and the protection of participants for clinical studies.
  • Best practices and ethical guidelines by industry, including contract research organizations, should build upon these requirements.”

She made “a call to action for manufacturers to assure access to generic drugs by requiring industry to have:

  • A culture of Quality.
  • Practices that ensure the integrity of manufacturing and bioequivalence data.
  • Transparent quality systems that enable investment in reliable and quality producers.”

Discussing the fact that 77% of the biostudies submitted in ANDAs during GDUFA II from October 2017 – September 2022 was conducted in India, and she had a slide right after that factoid, that noted the need to ensure data integrity:

  • The FDA requires high-quality data that is accurate, consistent, and reliable.
  • Poor data quality undermines the ability of the FDA to rely on appropriate analyses as part of the drug product approval process.
  • The FDA requires that industry maintain integrity of bioequivalence data throughout the data lifecycle.
  • Unreliable or manipulated data results in serious consequences:
    • Untitled action letter from the FDA to affected Contact Research Organizations (CROs).
    • Adverse outcomes for global public health (i.e., delay in the access to drugs).
    • CROs and manufacturers lose credibility and face substantial economic burden for conducting new studies and audits by independent third parties.

There was a follow-on slide which was entitled, “Call to Action – Data Integrity” asking manufacturers and CROs to:

  • Create a culture of Quality.
  • Emphasize that this is an important core value for the organization.
  • Expect everybody to be responsible and accountable for data quality.
  • Inform the FDA of any data quality concerns promptly.
  • Do not go to a bidder with questionable quality practices.
  • Think beyond inspections.

While these comments may have been precipitated by fairly recent data integrity issues found at two CROs in India requiring ANDA sponsors to, in many instances, repeat the BE studies that were conducted in support of the original ANDAs, the Agency has seen data integrity issues in lab data and manufacturing records that also prompt this call to action.

Her presentation also included a slide that showed improvement in time-to-approval of ANDAs over the course of the three iterations of GDUFAs that appears below:

 

 

While the numbers have improved for median and mean time, she also noted that 40% of ANDAs are being approved in two review cycles, which means that still 60% of ANDAs must undergo at least three or more review cycles before approval.  This is an area that I believe the FDA needs to pay more attention to, especially given that first-cycle review numbers for NDAs are in the range of 89-92%.

One of the other significant items she addressed was the removal of a fed bioequivalence study requirement for 864 products based on the final M13A ICH Guidance.  This will provide a critical cost saving to sponsors but will not likely make the CROs very happy.

Another issue that has been a thorn in the side of industry may be relieved by a soon-to-be-released pilot program to increase transparency.  So, what is this brave new program? – well, at times, there are scientific issues that may either be related to a single application or most likely a group of applications (e.g., the nitrosamine issue) and firms are kept in the dark sometimes for months on end about the issues and about the delay in approval.  Under the pilot program (details yet to be announced), the OGD will try to let firms know what and why the delay is occurring.  The OGD is hoping this transparency will provide some welcome information to sponsors whose applications are stuck in apparent limbo.

From Day Two at GRx-Biosims, Dr. Sarah Yim, Director of the Office of Therapeutic Biologics and Biosimilars, had a fireside chat with Giuseppe Randazzo, Senior Vice President, Sciences and Regulatory Affairs, at AAM.  The takeaway from the session was that, with few exceptions, the Agency, based on experience post approval, the advancement of analytical and scientific testing, and a “groundswell of information that tells us that we can streamline the approval process,” gives the FDA confidence that biosimilar are interchangeable.  Dr. Yim did say that, because of the current legislation, we must make that determination on a case-by-case basis and if there is a particular biosimilar that raises a unique issue, the Agency may need to ask for more information; however, with what the FDA has learned from post-approval marketing experience, that would seem to be the exception rather than the rule.  When asked if the wording of the statute might present a problem, Dr. Yim basically said, “that is what the FDA has been doing as they take all the scientific data into account before an approval decision is made on a product.” “We just need to follow the science,” Dr. Yim stated.

That’s it for today, we will be back with you shortly with other news from the AAM meeting.