A recent initial investigational new drug (IND) submission that Pearl Pathways prepared for a client caused me to think about the “perfect” IND. How might one define a perfect IND? In a previous job I held, there was a company Vice President who thought a perfect IND meant receiving zero questions from regulators. That is an extremely rare occurrence. Reviewers demonstrate that they have done their job by asking questions of the sponsor; so, it is unusual to receive a Safe-to-Proceed designation for an initial IND without receiving some questions.
Here’s something to consider: it is possible that if you did not receive any questions, it might be because you over-committed in the clinical and chemistry, manufacturing, and controls (CMC) sections of the IND. Therefore, these are commitments that you and your team would be responsible to maintain.
Defining the “perfect” IND
So, what do I mean by the perfect IND? I believe it is a document that is clear, understandable, and easy for the reviewer to read with a minimal number of mistakes. Every file is present in the IND electronic common technical document (eCTD) backbone. Every link moves to the right place and every number in the Module 2 Summaries matches the number in the corresponding study report. A perfect submission.
Wait — do you mean that every submission that you work on is not perfect in the sense described above? The best answer that I have is “I don’t know,” but at Pearl Pathways we do everything in our power to eliminate errors. Files in the eCTD backbone are checked for quality control (QC) against a list that is developed in partnership with the client. How many files are in an IND filing? It depends (which is always the right answer, by the way). The primary variable in the number of files is how many nonclinical reports are included, but a ballpark figure is between 100 and 200 files in an IND submission.
We also QC the numbers in the Module 2 Summaries against the corresponding nonclinical study reports. How many numbers are we talking about? Once again, it depends, but 50 to 100 individual values are in the ballpark.
And then there are the hyperlinks. And remember, we’re not just talking about intra-document links (e.g. see Figure 5), but inter-document links as well (e.g. the batches on stability were tested against the specifications found in Section 5.1). Each link should be checked to ensure that it goes to the correct location. And while we QC the links, we also look for intra- and inter-document links that should have been made but were inadvertently missed. How many links do we have to check? In a typical IND, hundreds. I haven’t even mentioned missing words or typographic errors.
The human (error) element of an IND
Why all of these quality checks? Because our clients are human and so are we, and humans make mistakes. So, what is a perfect IND submission? A perfect IND is not one that doesn’t receive any questions from regulators nor is it a document that has zero mistakes, although that is what we aim for every time. In my opinion, a perfect IND submission, or an investigational device exemption (IDE) for medical devices, is one that tells a clear story of:
- why a new drug or device has a high probability of efficacy,
- how it was manufactured to ensure the quality of the clinical trial drug product or device,
- and how it will be evaluated in clinical trials when administered to humans.
Hopefully, these trials will provide results demonstrating that the drug or device will improve people’s lives. If you decide to partner with Pearl Pathways to tell the FDA your IND story, we believe that we can speed your drug to patients. And that would be perfect.