Amanda Houck Miller
Gary Pekoe, Ph.D.
Strategies formed early help keep investors and partners happy as well as create a smoother development path.
Early-stage emerging technology companies are very fragile. They have very specific product development needs based not only on their technology and their financial status but the culture inherent to such companies. They need close guidance not just with a few regulatory items but with the entire path to the IND application. Very often they have no understanding of or experience working with the FDA and are usually undercapitalized. They need to multitask and balance the generation of new ideas with staying focused on the company direction.
Such early-stage firms have investors to please, funds to raise, milestones to hit, burn rates to control, and a finite existence looming if they are not immediately successful in these areas. Add to this their need to understand and manage product development, and it becomes an overwhelming situation.
These companies cannot afford to receive less than excellent attention the first time around, as they usually are not funded or resilient enough to start over. This is especially true in the current regulatory and financial environment, where the FDA is evolving as it sees more and novel technologies that in many cases have no precedent, and seed money is diminished or nonexistent.
While at a start-up biopharmaceutical company, it became apparent that work we contracted out to large CROs was often not prioritized or was pushed downstream to allow the CRO to focus on its large pharmaceutical sponsors for which it was designed. (This is not to diminish large CROs; they have their place and are an excellent fit with the large pharma culture.) In response to this a new CRO model was developed, in which a small, culturally similar CRO would focus on emerging pharmaceutical and biotechnology companies beginning very early in the development process—at the discovery stage if possible. The model was set up to allow the emerging pharmaceutical and biotechnology company to have the personal contact and product development attention given to large pharma companies in their culturally similar, large CROs.
Balancing Clinical and Corporate Goals
The most obvious issues may often be overlooked or neglected in the midst of the fast-paced, intense, stressful, detail-oriented world of the emerging technology company. These companies tend to be task-oriented and are focused on achieving the most imminent steps in their development process, rather than thinking big picture. Often that is because they have no experience with the road that lies ahead.
These companies need a solid albeit dynamic strategic regulatory plan (SRP). The SRP describes the roadmap to a certain point in time that makes sense for that individual company. This is based on not just the company’s clinical goals but on its corporate goals and milestones as well.
Very often an emerging technology company plans to take its technology to a specific development point and then partner or license it out. Funding milestones may exist that require the company to achieve certain endpoints that may be secondary to the most direct development path. For example, we had a client whose licensing agreement required them to initiate trials in two different cancer indications by a set date. They came to us to manage their development program in colorectal cancer, and we began providing updates to their investors and to the university from which the technology had been licensed.
Along the way we asked for a copy of the licensing agreement, so we could more fully understand their corporate development issues, since no SRP was in place. It was at this point that we discovered the clause requiring the second indication, which their management team had either overlooked or forgotten. We confirmed the issue with the university, which was adamant about the client adhering to the agreement. We had barely enough time to get a second IND filed and the clinical trial started.
Had we not intervened, the client would have been in serious trouble within a few months, without the resources to extricate themselves. A clear, comprehensive SRP would have obviated the need for this scramble, as such information about corporate development milestones would have been elucidated.
Developing a Robust Regulatory Plan
An SRP should be a top priority for emerging technology companies, because it is a company’s process of defining itself. It helps detail the firm’s strategy for product development and testing, its focus, the interested indication(s), and regulatory approval within the FDA or other government body. The SRP gives a company the ability to make decisions and allocate its resources to achieve the company’s clinical and corporate goals. It provides a clear pathway that can be used to chart the product-development course over time.
A good SRP allows a company to determine which route would be the most cost-effective, time-efficient, and likely to succeed. At the end of the day a well-developed SRP takes the company from discovery to IND to its final goal and very often enables the company to see itself as a real entity and not a group of individuals with great ideas, a technology, and a notion of the next few steps in development.
Involving the FDA early in SRP development assists with truly knowing the proper path, can prevent the company from going down blind development alleys, and lends high credibility when talking to potential investors or partners. The ability to say to a potential investor that one has FDA feedback on his plan is a tremendous advantage over a plan that has not been validated.
The SRP comes in many sizes. The document can be quite extensive, giving details as to what preclinical tests are needed, sample size estimates for clinical trials, timelines, precedents, suggestions for clinical study sites, and much more. Alternatively the SRP can be abbreviated, giving a rough outline of which division in FDA will review the application, a timeline, and an approximate cost estimate. At the same time the SRP must remain cost effective for the sponsor, so pricing for an emerging technology company with minimal funding is a consideration. The SRP is tailored to the emerging company’s budget, corporate needs, and technology. The key is to understand the time and cost necessary to achieve the goals as well as to understand the precedents and potential roadblocks or speed bumps along the path.
Working with a solo regulatory consultant is not necessarily cost effective in the long run. No regulatory person is experienced in everything, and plans succeed with many advisors. A small team headed by the regulatory consultant is essential. The other members will review the SRP for clarity, sensibility, and focus. The team is tasked with thinking outside the box for the sponsor and if possible will develop a less traditional or more aggressive strategy than usual.
The team must be able to truly think like the sponsor and understand the needs that emanate from the emerging company culture. It is also important to understand and provide the one-on-one contact and attention for each individual idea or product.
The team’s ability to provide continuity of service while the company moves along the pathway is also very important. Having the ability to consult on an ongoing basis with its author gives the sponsor a feeling of security. While the sponsor focuses on its day to day tasks along the path, the regulatory consultant monitors and coordinates each step of the SRP. The regulatory author should also constantly be reviewing new guidance documents and regulations that are developed and will continuously work this new information into the dynamic SRP; most sponsors don’t have time for or sufficient knowledge about this task.
The sponsor thus will have fewer sidetracks along the way and can feel safe knowing that with the regulatory consultant, unexpected events can always be re-evaluated and the SRP adjusted.
The interaction between the emerging technology company and CRO can be initiated at any time during the development of a product. This interaction is most successful, though, if initiated as early in the process as possible, when an idea for a product is developed. This allows the team to lay out the best SRP possible, thus helping pave the way for successful product development.
Gary Pekoe, Ph.D., is president and CEO and Amanda Houck Miller is regulatory affairs manager, Arkios BioDevelopment International.