A Complete Response Letter (CRL) from the FDA due to manufacturing issues can destroy a biotech. CEO Ron Cooper warns leaders to invest heavily in Chemistry, Manufacturing, and Controls (CMC) early, even when the cost exceeds the clinical trial spend. This early investment in professionalizing CMC is critical to de-risk the company's future.

Voyager CEO Al Sandrock supports the FDA's use of accelerated approval for severe diseases but argues it must be coupled with industry accountability. He praises Amelix for voluntarily pulling its ALS drug after a failed confirmatory trial, framing such responsible actions as essential for maintaining the FDA's willingness to be flexible with approvals based on surrogate endpoints.

Amidst growing turmoil at the FDA, a viable strategy is to "invest around" the risk. This involves prioritizing companies whose drugs show clear data on well-understood, validated endpoints, as these are most likely to navigate the current political environment successfully, regardless of leadership changes.

Bio is creating a formal system for biotech companies to report challenges with the FDA. Bio will synthesize this feedback monthly and present it directly to FDA leadership, creating a novel channel to elevate systemic issues and improve accountability.

Successful biotech leadership requires a clear decision-making hierarchy. Dr. Bahija Jallal advocates for a framework where patient welfare is paramount, followed by scientific rigor. Financial success is treated as a byproduct of excelling in the first two areas, not the primary goal.

Isaac Oppenheim's mission to restore his grandfather's dignity after struggles with OAB provided the deep-seated motivation needed to persevere through the grueling FDA and CMS approval processes. This personal connection is a critical asset for overcoming inevitable entrepreneurial challenges.

In high-stakes regulated fields, documentation like FMEAs is not red tape. It's a critical tool for understanding failure modes, mitigating risks, and ensuring product viability and patient safety, especially for a startup where one recall can be fatal.

In high-stakes fields like medtech, the "fail fast" startup mantra is irresponsible. The goal should be to "learn fast" instead—maximizing learning cycles internally through research and simulation to de-risk products before they have real-world consequences for patient safety.

A company's purpose statement serves as a 'GPS' in rough waters. Johnson & Johnson's patient-first credo guided its decision to pull all Tylenol during a poisoning scare. This decisive, purpose-led action ultimately strengthened trust, demonstrating how a clear 'why' enables effective crisis management.