Today’s episode is hosted by none other than Janet Overvelde, Innovaderm’s Senior Director, in Project Management for the occasion of the 2024 AAD in beautiful San Diego, CA. She interviewed Staci Ellis, the Vice President, and Head of Regulatory Affairs at RegDev Inc. Staci is a strategic and diligent leader in Regulatory Affairs, with experience spanning from early to late stages in small to mid-sized companies.

We will be exploring the guidelines for a successful investigational new drug (IND) filing in the US, focusing on 4 key aspects:

1. Early Engagement and Strategic Planning
2. Aligning Dose Data with FDA Safety Assessments
3. Effective IND-Enabling Pharmaceutical and Tox and Chemistry, Manufacturing, and Controls (CMC)
4. Compliant CMC

Early Engagement and Strategic Planning

How can a Sponsor help ensure the success of a US IND filing?

Initiating an early dialogue with the Food and Drugs Administration (FDA) through the request of a pre-IND meeting is suggested. This allows for the presentation of your compound and program to the FDA review team and receiving valuable feedback before an IND submission. The time invested in requesting, preparing a briefing package, and awaiting the FDA’s response can help mitigate program delays by addressing potential deficiencies before an IND filing. This increases the chances of success for IND approval. A pre-IND meeting facilitates alignment on the design elements of your first in human study. Achieved by preparing a well-written briefing package and sharing a draft protocol for the FDA to comment on key study elements. These include your choice of primary and secondary endpoints, possible inclusion of a biomarker, agreement with the patient population defined in your protocol, planned statistical analyses, starting dose, and overall trial design. Furthermore, the meeting provides an avenue for obtaining early FDA feedback on the clinical development program.

Aligning Dose Data with FDA Safety Assessments

What steps should be taken to ensure the FDA breeze that our data will support our starting doses and ascending doses?

In the briefing package supporting the meeting, inclusion of data justifying the starting dose and dose escalation for the study is crucial. Defining plans for determining appropriate recommended phase 2 doses and regimens for the next study is also essential. It is important to ask the FDA this particular question before submitting an IND so that you can ensure that they agree on the starting dose, dose escalation plan and regimen are supported by data that not just you but also the FDA finds acceptable to the safety assessment regarding subjects’ exposure. At this point, FDA may not be familiar with your program or the sponsor. If FDA has safety concerns, whether related to dosing or any other aspect of your study, it is beneficial to learn this now so that these elements can be modified or further supported with data in the actual IND filing. Learning of any deficiencies or safety concerns from FDA prior to actually filing an IND can prevent potential delays to the program overall, or even prevent a clinical hold based on FDA’s initial review of the IND. If that were the case, net saving in time will favor the program by opting for the meeting originally.

Effective IND-Enabling Pharm/Tox and CMC

How can we ensure the FDA agrees that our data will support our starting dose and ascending doses?

This information requires description in the pre-IND meeting package, with appropriate questions posed to the FDA to gain useful and actionable feedback. It is important to ascertain whether the FDA agrees that all work has been adequately conducted and the data could support your first in human study, or else understand directly from the FDA what may be unclear, unclearly presented, or possibly incomplete. In other words, it is crucial to understand the FDA’s concerns and how these concerns can be mitigated in the IND filing.

This means that the sponsor needs to describe the IND enabling non-clinical pharmaceutical and tox studies that have been conducted and are in progress, and the data to support the clinical study that is proposed to the FDA and IND. This information should be presented in the briefing package in a manner that conveys that the IND filing will meet the FDA’s expectations, all requirements will have been met, and there will be no potential safety concerns left unmitigated.

Compliant CMC

What about the chemistry, manufacturing and controls information? How do we ensure this information is conveyed clearly and meets FDA expectations?

From a CMC perspective, the information in module 3 of the IND filing needs to be accurate and complete, but not overly detailed, depending on the phase of the proposed study. In the pre- IND-meeting briefing package, it is important to explain the plan for the IND, provide the scientific rationale that demonstrates control of the drug’s identity, strength, potency, purity, quality, and health safety.

The agency will focus on the review of the IND on whether the drug substance center product can be consistently manufactured in compliance with good manufacturing practices (GMP) and whether the drug is reflective of what was used in the supportive non-clinical study. At the end of the day, the primary concern in a US IND is subject safety. This will be evident in the data presented, the quality and consistency of your manufacturing information, and the design of the clinical trial.

The pre-IND meeting provides a valuable opportunity to ask relevant questions of the agency and receive feedback. This allows for the mitigation of risks that could result in the IND filing not being cleared in 30 days and having to start over. This could result in significant time and financial costs. Therefore, requesting a pre-IND meeting at the onset is highly recommended.

As we conclude another illuminating episode of Phase Forward, we find ourselves at the crossroads of science and progress. Remember that behind the jargon and statistics, lies stories of unwavering commitment, meticulous observation, and the pursuit of evidence that shapes our understanding of health and disease. Stay at the forefront of knowledge and innovation and follow Phase Forward on your preferred platform. My name is Valerie Coveney. Thank you for joining us. Until next time.

Let’s shape the future of research and make a difference in the industry, gain Innovaderm’s support in your upcoming trial and propel your study to new heights. 

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