Critical steps to preparing an IND

So you’ve already invested in and cleared the initial discovery and development process for your new drug. You’ve either completed or are still working through the nonclinical research phase of development to test the drug’s potential safety and toxicity—and you are starting to plan for clinical testing in humans. But before moving to this next stage of development, you need to submit an Investigational New Drug (IND) application to the FDA. An IND is an important step because it sets the tone for all of your future FDA interactions. A well-planned application can serve as the foundation for a smooth and efficient approval process, while a poorly composed IND can result in costly delays and rework. Here are key steps to help ensure your IND application gets your product off on the right foot.

1) Understand the makeup and purpose of your IND application

In general, an initial, first-in-human IND must contain a summary of the following information to be submitted for review by the FDA, so the agency can in turn make a determination that it’s safe to proceed to clinical testing.

• Chemistry, Manufacturing, and Controls (CMC) data– This information provides a summary of the composition, manufacturer, stability and controls used for manufacturing the drug substance and drug product. The FDA is looking for data to confirm that the sponsor can adequately and consistently supply the drug at a specified quality.
• Nonclinical data – A summary of the nonclinical pharmacology, pharmacokinetic, and toxicology studies that have been conducted. These studies need to provide ample safety data (including exposure data) to support the clinical protocol. These data are used to set the starting dose for the initial clinical studies.
• Clinical protocol – The CMC and nonclinical data should be sufficiently detailed and provide enough specific information for FDA reviewers to make a determination that human subjects would not be put at undue risk when exposed to the investigational drug, as described in the clinical protocol. It's important to understand, and completely prepare, each of these IND components. Failure to do so can significantly slow down your drug's path to approval.

2) Establish a knowledgeable project team that has deep and broad scientific expertise

The drug development process is becoming increasingly specialized, and the development pathway that works for one drug may not work for or be applicable to another. An experienced product development team – one that has broad scientific expertise and a track record of successfully pursuing an array of development pathways – will understand the nuances of this process and will be able to provide advice on the specific studies, both nonclinical and clinical, that will be needed to support your particular drug.

The team can also provide valuable guidance on the safety data needed to support the IND. The number one reason why INDs are placed on clinical hold by the FDA is that the therapy’s proposed protocol does not adequately describe how the safety of the subjects/patients will be ensured in the clinical study, so special attention should be given to addressing this.

3) Begin with the end goal in mind: Perfect the Target Product Profile

The project team you assemble is also critical to the success of your program because it will guide the development of the Target Product Profile (TPP).

The ultimate goal of an effective development program is to identify and gather the data needed to support a marketing application that contains all desired prescribing information for the planned indication. The TPP is a means to communicate the primary indication, delivery mode, dosage form, and patient population that the compound may treat. It should also communicate the route of administration and dosing regimen, safety profile of the product, and efficacy. The TPP then becomes the roadmap for the development program – it guides which studies will need to be conducted to support the ultimate approval of the product.

Developing a TPP can be used to facilitate early discussions with FDA regarding the nonclinical and clinical programs that will be needed to support the labeling. For companies looking for funding and/or partnering opportunities, the TPP also serves as a concise document that can be used to communicate the development pathway for the program.

4) Communicate with the FDA as your partner

The FDA’s main role during earlier stages in the drug development process is to provide guidance to sponsors to help ensure the compound is reasonably safe before moving forward into clinical testing. Ideally, you’ll work collaboratively with the FDA throughout the drug development process, keeping in mind that you share the overall goal of ensuring that your drug is safe and effective. It’s important for your communications with the FDA to be both transparent and timely, and appropriately planned for each critical phase of drug development.

By its own admission, the FDA has limited resources – and each year, the agency engages in thousands of communications with sponsors during the IND phase of development. That means it’s essential for all communications with the agency to be conducted as efficiently, clearly, concisely and consistently as possible. It’s also why your development and regulatory team needs have a strong working understanding of the practices that are most likely to drive collaborative and responsive FDA relationships. Getting started on the right foot with the FDA is key to expediting your pathway to approval.