Entrepreneurial Pharma: Confronting the Adage, “Experience Is Something You Get Just After You Need It.”

During my 23 years working in the entrepreneurial pharma environment I have witnessed many lessons learned and I continue to see many companies focusing primarily on reaching key funding milestones while neglecting good drug development practices. This is a mindset that can cost them dearly and deliver experience after it’s needed! It is crucial for entrepreneurs to focus on creating a strong value proposition for the company, attracting the top investors and scientific advisors and moving quickly to key milestones and the additional funding they provide. It’s the nature of the environment. However, at the same time, pharma development requires early and consistent compliance with regulatory guidelines and quality assurance standards and exemplary collaboration skills to enable critical preclinical and clinical trials. The paradox is the need to move quickly AND carefully comply with regulatory requirements and solve technical challenges. This can create confusion when weighing the “must haves” and the “nice to haves”. Often, many important elements are considered “nice to have”. Many entrepreneurs have trouble discerning which is which. Usually, a lack of time or staff or cash is reason for projects moving ahead without the “must haves” like proper documentation or quality checks. In addition, the outsourcing environment is something that is both art and science, something not fully appreciated by all entrepreneurs. Staffing at outsourcing firms varies in expertise, especially in the areas of regulatory strategy and documentation. This requires experienced oversight by the sponsor company.   Here are some real-world examples of my observations of companies that failed to focus on the fundamentals and paid the price: When I was working as and independent...

505(b)(2) Regulatory Submissions Require Flexibility, Creativity and Resilience

The FDA Guidance describing the pathway for development and approval of a 505(b)(2) application covers a lot of ground, but as with any Guidance, it serves only as a general outline. A key element of this Guidance is described in Section II.B.2. “For changes to a previously approved drug product, an application may rely on the Agency’s finding of safety and effectiveness of the previously approved product, coupled with the information needed to support the change from the approved product. The additional information could be new studies conducted by the applicant or published data. This use of section 505(b)(2), described in the regulations at 21 CFR 314.54, was intended to encourage innovation without creating duplicate work and reflects the same principle as the 505(j) application: it is wasteful and unnecessary to carry out studies to demonstrate what is already known about a drug.” In my experience the phrase “coupled with the information needed to support the change from the approved product.” is not always straightforward or predictable. The negotiation with FDA involves the product profile desired by the Sponsor and the historical approval and market information within the Agency. Perhaps the best way to examine some potential challenges and diversity of requirements is to present a few real life situations. I discovered these challenges when I joined a virtual company, replacing the Head the Research and Development, Quality and Regulatory groups, where my predecessor, a tenured generic manager, approached the regulatory requirements for a 505(b)(2) NDA from a generic application viewpoint. One NDA had already been submitted for an injectable product but was given the “Refuse to File” designation...