Helping Our Best Clients Accept A Healthy Level of Regulatory CMC Risk (Ed or Op-ed?)

Helping Our Best Clients Accept A Healthy Level of Regulatory CMC Risk (Ed or Op-ed?)

Our Best Practices for Communication Between IND Sponsors and FDA During Drug Development

This op-ed, short for “opposite the editorial page”, is a written prose piece provided here today which expresses the opinion of our business and this blogger.

Ask questions rather than lecture to guide IND Sponsors form their own conclusion.

CMC consultants can help educate investigational new drug application (IND) sponsors (Clients) with extreme attitudes about risk to rethink their approach.

To assess a client’s risk tolerance, we use many tools. We formulate reviews, envision worst case scenarios and give history lessons on our experiences.

Through these exercises, we gain a better understanding of a client’s appetite for risk in their development program. But what if that appetite is unhealthy?

Some individuals have an off-kilter sense of risk. They may play it overly safe and refuse to make even the most prudent bets on their development program. Or they may gamble willy-nilly, putting all their chips on wildly unpredictable long shot CMC strategies and preceding advice.

When working with someone whose risk tolerance is too extreme (in either direction), we as consultants need to recalibrate how the client goes about attaining important goals. Helping our clients adjust their attitude and accept an appropriate amount of risk to meet their objectives can determine whether they ultimately achieve success, i.e. successful marketing approval and with that, peace of mind, a feather in their cap, and increased shareholder value.

“It happens often that people want to take too much or too little risk because the experience has not been there in terms of development activities and the risk involved”

For example, “I want to get a seamless and fast approval, but I don’t want to spend a dime.” We respond by teaching clients about the risk-return relationship and other regulatory drug development principles at each phase.

Like many consultants, we find that some clients lack a firm grounding in risk assessment. They may claim that they can withstand stomach-churning unpredictability and keep their eyes on their long-term objectives, only to panic after a minor setback to the program, i.e. A failed batch. Or they may opt for the most conservative path, only to question later why their program is so costly yet still behind schedule.

Questions, Not Lectures

Rather than lecture clients on why their approach to risk is misguided, we as consultants tend to favor a more interactive strategy. Through gentle questioning, we try to uncover one’s perspective about their development program.

To initiate this conversation, we talk with our clients about their receptivity to risk and then follow up with prompts such as, “What led you to that strategy?” or “Help me understand where that thought process comes from.”

That opens the door so that we can hear their story. They might say that in a past life they were involved with a failed product because of CMC issues and they’re hesitant to take any risk. From there, we educate.

Teaching clients to rethink their risk tolerance requires delicacy. You can’t just say, “Your way too extreme”! and/or “You need to totally change your perspective.” Clients may chafe when subjected to admonishment.

It’s better to lead individuals to conclude for themselves that they need to reset their risk appetite.

We encourage them to find resources on their own. We often say, find three different regulatory drug development strategies and then let’s go over the pros and cons of each one. That allows us to have a more informed conversation.

It’s also useful to probe a client’s risk tolerance in new ways. Traditionally, we as consultants ask our clients whether they’d cut back on drug development, if the company, say, was short on resources or cash. A better tactic is to ask them to guess how much generating some useful data and dialogue with their partners (CMO’s and the Agencies) will gain them over this timely and sensitive period — and how confident they feel about this.

Keeping clients engaged in a lively back-and-forth discussion about risk prevents consultants from barking orders such as “You should do this!” or even worse “You need to do this!”.

When clients participate in the decision-making process, they’re more apt to buy into well thought out recommendations.

Appeal To Logic

A consultant that I hired once in the past, told me that he once said to one of his clients, who refused to take even a relatively small amount of risk, “We’ve set goals. To get there, you will need to take a bit more risk. Are you willing to do that?”

If not, he plugged in information into a Gantt chart to project how they’ll fall short of their goal. We ask “Is it more important for you as an IND Sponsor to achieve your product approval goals and accept a certain level of risk? Or is it more important to reduce what your programs goals are?”

Almost always, clients accept taking a bit more risk in their long-term planning. Most people are logical if you present it in a logical manner.

For those client’s intent on risking too much, we usually walk them through the consequences of a botched decision. Often, one member of most any IND Sponsor partner argues for more risk than the other.

If someone is too aggressive but not irrational, we say, if we shoot for only the quick and dirty, there’s a bigger chance we’ll face bigger setbacks. Then we share the painful experiences and case studies. That’s an easier conversation than getting people to be more aggressive.

The purpose of this posting today is to describe a bit about how we operate as a consultancy business and some best practices and procedures for timely, transparent, and effective communications between IND sponsors and the FDA and other agencies at critical junctures in drug development, which may facilitate approval and earlier availability of safe and effective drugs to the public.

This applies to communications between IND sponsors and FDA during the IND phase of drug development, including biological product development. Let’s talk soon about:

  • FDA’s philosophy regarding timely interactive communication with IND sponsors as a core activity
  • The scope of appropriate interactions between review teams and IND sponsors
  • The types of CMC advice appropriate for IND sponsors to seek from FDA in pursuing their drug development programs
  • General expectations for the timing of FDA response to IND sponsor CMC inquiries


The key is to not waste time on compounds that later may need to be scrapped due to CMC related issues. Creating a CMC scorecard upfront can identify problems early and allow time for solutions. You can identify, assess and rank risks you might not have ever imagined existed with the use of a quantitative approach that will assure compounds make it to approved products.
DSI can teach you how to use a quantitative-based scoreboard approach that will enable you to identify drug program risks and provide you with a method to evaluate critical areas in the drug development process.

DSI provides regulatory, technical, and project management consulting services to healthcare product companies that manufacture and/or market pharmaceuticals, biopharmaceuticals, and cellular and gene therapy products.

Since 2007 we have provided our clients with innovative strategies and exceptional quality work products intended to enhance product development, approval, and marketing presence.

Whether advocating CMC strategy, directing CMC operations or developing CMC submission content that represent the best interests of emerging biotech, we focus on the critical CMC issues and build programs that enhance development.