Beyond GRAS

By Michael Baumann, Integrated Project Management Co. | March 2, 2011

Creating a pathway to regulatory success

When developing a truly unique functional food, the more robust your development program, the stronger the claims you can make. The stronger your claims, the more you can differentiate your product and capture market share. How can you take your product to the next level? By creating an airtight but flexible process to guide your development effort. Careful planning and rigorous execution enable you to design effective clinical trials, navigate complex regulatory requirements, drive cross-functional teamwork and solve problems quickly. The results: a timely launch and the best possible labeling.
Transforming an Iconic Product
A global powerhouse had a top-secret product under development. By adding an obscure but promising nutraceutical ingredient, it sought to boost the performance of one of its iconic brands, transforming it from a conventional product into a revolutionary functional food. This product would not only be “new and improved,” but would also provide first-of-its-kind physiological benefits. However, due to a series of missteps—including a quarter-million-dollar clinical trial riddled with errors—the firm faced a timeline delay costing $6 million in lost opportunity.
What Went Wrong?
As with most disasters, the breakdown was caused by a faulty system, not one person or a discrete event. So what led to the collapse?
While the clinical group had performed safety studies before, efficacy studies were new to them, but also necessary to support product claims. The firm hired consultants from the pharmaceutical world to design the trials, which was sensible. However, while the consultants knew drugs forward and backward, both they and the internal clinical staff were not thoroughly versed in food-related regulatory requirements. Due to the high cost of efficacy trials, they decided to launch their study outside of the U.S. to economize—this is a common practice in the pharmaceutical industry. After all, arthritis affects someone in Minsk the same way it affects a person in Miami. However, FDA requires U.S.-based trials for U.S.-sold foods, since diets vary so vastly across countries. So test results from people eating mostly fish and rice, say, are unlikely to apply to the average burger-eating, soda-swilling American. Why didn’t anyone catch the error?
The firm’s regulatory affairs leader was fully aware of FDA’s requirements. But, as in many large corporations, functional groups became isolated. There was no formalized process for sharing information or making collaborative decisions. As a corollary, it was difficult to achieve consensus when conflicts arose, which strained relations—and communications—across functions. Moreover, as a busy senior executive, the regulatory affairs leader did not routinely attend project team meetings, missing discussion of the faulty clinical plans. So the regulatory knowledge base continued to reside almost exclusively with one person, with no process for disseminating critical information, which simply fell between the cracks.
Beyond the regulatory miscue, project communication was hobbled in general. The project’s day-to-day technical lead said that reports on project status were routinely outdated by as much as three or four weeks. That meant he had no way to track real-time progress, coordinate activities or detect emerging issues.
A contract research organization (CRO) had been engaged to execute the clinical trial on the ground. While the trial’s design was top-notch, the CRO wasn’t conducting sufficient follow-up with study investigators to ensure that they were following the protocol properly—turns out they weren’t. In fact, protocol deviation was so significant that it invalidated the primary outcome of the study and the results looked too good to be true—they were. Transcription errors had skewed the data, which the CRO hadn’t fully reviewed before releasing them to its client, who immediately questioned the outcome. After the trial was complete, the CRO inadvertently allowed the principle investigators to delete the primary study data from their computers. All that remained were results.
Clearly, the contractor was in over its head. And because there was no system for vendor oversight, no one in the company knew it until a lot of money and months of work had been wasted.
Although the company had arranged for sophisticated blood testing in the U.S., the CRO was unable to ship the samples from the study country. The host government required preapproval for such a transfer, so the samples were never released.
Charged with securing a U.S. study site for a new efficacy trial, the CRO found itself floundering. With no backup plan, it suggested instead that the company change its study protocol.
Incomplete planning—espeically for risks—left the company in the lurch. The firm also lacked an integrated project plan. The clinical group had a plan. So did regulatory and packaging and manufacturing. But each plan was separate and didn’t interconnect with the others. That doesn’t work when executing a complex regulatory project. Clinical studies feed into product claims, and product claims lead to labeling and packaging, which depends on type of manufacturing process. How would functional groups collaborate? When and where were the handoffs? If a problem occurred at one link in the chain, how would it affect the others down the line? No one knew.
The Turning Point
Millions of dollars were in peril. The project was in crisis. But all was not lost. The firm regrouped to examine its options. To salvage what it could, the company decided to pursue a process-driven approach based on project management best practices.
Build a ‘living’ project plan. “We’re great at planning, but we don’t follow the plan.” So said several employees, and it was no wonder. The company’s plans consisted largely of static spreadsheets listing dates and milestones. Once goals or activities changed (as they inevitably do), plans became essentially obsolete, and people were left to their own devices. A skilled project manager with drug/device industry experience led the initiative to retool the company’s product development process.
Map interdependencies. The project manager first asked the team basic but critical questions: What regulatory, commercial and manufacturing requirements must we meet? What are our deliverables? What activities are required to deliver them? Where are the logjams, and how can we remove them? Using the detailed findings, together they developed a plan that interconnected all activities—from data analysis to package design—required to bring the product to fruition. Team members now had a clear map to guide who did what and when, within and across functions.
Enable sound decision-making. Since all activities and dates were linked by a software program, any potential change—which the project manager would insert real-time—triggered an update across the plan. The team could then analyze what kind of impact that change would have on the project goal. If an unexpected illness slowed the creation of the FDA dossier, was there wiggle room in the timeline, or would that mean missing a critical submission milestone? If the latter, what was the cost/benefit of engaging an additional professional to complete the document? Not only a project guide, the plan served as a robust decision-making tool.
Foster team unity. The process of creating an integrated plan was one way of alleviating cross-functional conflict, which had been an insidious factor in the project’s breakdown. By focusing everyone on how to achieve mutual goals, the project manager facilitated a more collaborative environment. Do deliverables and due dates work for all parties? If not, why? What’s realistic? What’s not? Creating group buy-in on how to proceed helped dissipate suspicion and create a more unified team. That, in turn, eased communications overall.
Orchestrate communications. A highly structured communications system was created to ensure that project members, spread across multiple sites, were neither bombarded with unnecessary information nor inadvertently left out of the loop. Together, the team identified which functions should attend certain meetings, and who should be copied on which communications. They created project dashboards, constantly updated, to summarize the latest critical activities, as well as other communications tools to inform and apprise. As a result, team members knew what they needed to know on a real-time basis and could act far more effectively.
Create centralized repository for project information. To keep the project on track, it was critical to have quick access to documents and data, which were scattered throughout paper and online files. In response, the team created a centralized password-protected e-room, which housed everything from meeting minutes to regulatory reports. No more circuitous searches or guessing which draft was the latest. The e-room files were highly organized, with an e-room “master” to keep it that way. Team members could share documents by simply emailing a link. Once people realized they could find what they needed with a click of the mouse, the pace of work picked up almost immediately.
Drive execution. The new project plan was now in place. But even the best project plan fails unless executed with rigor. The project manager’s role included ensuring that the team successfully completed each day’s activities. Is an investigator late on delivering data? Did a technical snag emerge in the manufacturing process? When a problem arose, the project manager facilitated a swift resolution by the team. How serious is the issue? What impact, if any, does it have on the timeline or budget? What options do we have to address it, and what does each of them cost? Such an objective trouble-shooting process served to maximize outcomes and ratchet down tensions.
Assess risks in advance. What if clinical enrollment lags? Data miss the mark? Budget is cut? Identifying risks and establishing contingency plans before a project begins enable a faster, more effective response—and may prevent the problem altogether. Although the company’s efficacy trial had already imploded, the team sprang into problem-solving mode using a decision-point process.
•Did their safety data satisfy GRAS requirements? If not, the project should be killed. The data were strong.
•Since the efficacy data couldn’t support an enhanced product claim, did scientific literature exist on its nutraceutical ingredient to support a lesser but marketable “baseline” claim? Yes, it did.
•Should they pursue an enhanced claim for future use? Yes. The ingredient had such potential that it was worth investing in a new study.
The team prepared the GRAS submission. They initiated marketing plans for a baseline claim. And they hired a new, vigorous CRO that was able to quickly secure a U.S. site for a new efficacy study. The company now had options — and a game plan.
Tenfold Savings in Capital Expense
The company’s newly structured, collaborative approach was yielding more and more benefits. The new product required testing to demonstrate that an exact amount of nutraceutical ingredient was present in each unit sold. The supply chain, quality, product development and analytical groups came together well in advance to explore how to accomplish this task. They had two options: buy a $100,000 HPLC testing instrument that required a highly educated (and expensive) professional to operate it; or send samples to a third-party lab, which required a 72-hour hold time in company warehouses, straining the firm’s just-in-time inventory system. Was there a third option?
The analytical group approached the problem as an exciting challenge. In the end, they created a simple test using a $9000 spectrometer, which could be operated by someone with a high school degree and produced valid results in about an hour. An HPLC test, while far more sophisticated, yielded unnecessarily refined results. Problem solved.
A Template for Future Success
With the FDA dossier at the agency’s door and existing scientific literature available to support baseline claims, the firm had its new product back on track. In the end, it lost only one month to delays, instead of the six originally anticipated. If its U.S. efficacy trial yielded stellar results, the company could enhance its claims even further.
Most important, the organization now had a well-defined yet flexible process that it could tailor to future nutraceutical product development efforts, for a smooth pathway to regulatory success.

About the author: Michael Baumann, project manager, Integrated Project Management Company, has led product-development projects in the biopharmaceutical, medical technology and agriscience/nutrition industries. He holds a PhD in tumor cell biology from Northwestern University and completed post-doctoral work at the John Hopkins School of Medicine. You can reach him at 630-789-8600 or mbaumann@ipmcinc.com.