Regulatory and Revenue?


How commercial and regulatory can achieve synergies.

With moderator NEIL GREENBERG Editor, Healthcare Sales & Marketing


Our panel of experts:


Vice President, Regulatory Affairs and Quality Angiodynamics



Vice President, Global Regulatory & Clinical Affairs LifeNet Health



Senior Director, Regulatory Affairs CR BardPc0150500

Let’s have a little sympathy for regulatory team, who get it from both sides. They’re charged with protecting the interests of life sciences companies by making sure you adhere to the laws and guidelines in place. At the same time, they are seen as a speed bump by those in commercial who want to get the product out the door with the best face possible.


Vice President, Global Regulatory Strategy AbbVie As our panel explains below, the regulatory departments think of themselves as your advocates. They, too, want to help marketing and sales promote products and make profits…without incurring lawsuits. So this article is our attempt to help commercial and regulatory understand each other’s point of view, and work together more efficiently.


Pricewaterhousecoopers (PWC) believes the global pharmaceutical industry will be worth nearly $1.6 trillion by 2020, and that the U.S. will experience 33% growth in the same period, due in part to the Affordable Care Act. China and Brazil are not far behind.

At the same time, Deloitte estimates the counterfeit drug market at $75 billion to $200 billion, and the World Health Organization (WHO) says that over 25% of medicines available in developing countries are counterfeit, resulting in 100,000 annual deaths in Africa alone. Good reasons why pharmaceutical regulations are increasing.

We have to help rein in the problem by being as compliant as possible. That’s why we need to partner with regulatory, and recognize that they are doing their best to help the companies we work for. See below for some useful advice.

In your experience, how do marketing and sales view regulatory affairs?

ANDREW STOREY: It takes a lot of effort from the Regulatory Affairs (RA) team to earn the respect of the commercial team. In the past, RA was viewed as a barrier to sales and was often used as a scapegoat when numbers weren’t met. This has evolved significantly, with RA in most companies becoming regarded as a full-on value-added partner in ensuring company targets are met. At Abbvie, there are extremely strong linkages between Commercial and RA, both on a regional and global basis.

GARY BARRETT: Marketing generally considers regulatory affairs as an obstacle to be avoided or ignored. This is due to a direct dichotomy in the philosophy behind each discipline. Marketing’s aim is to display an outcome, to sell an idea rather than a specific product. This is directly at odds with the “no marketing puffery” dictate from the FDA. RA is also intrinsically risk-averse and absolute in specifying a “thou shalt not” perspective. The reality is somewhere between these two perspectives. Recent legal cases where the FDA off-label decisions have been challenged under first amendment issues are likely to heavily influence long-term perspectives for both disciplines.

ROBERT GUZMAN: The marketing of regulated drugs, biologics and medical devices has evolved in recent years. Although these changes have been influenced by the introduction of social media and other electronic means of communication, the regulatory landscape has been a major contributor to these changes as well. The FDA, international regulatory bodies, and Ministries of Health are synchronizing their efforts in order to protect patient safety, promote ethical behavior, and better patient/HCP informed decisions when choosing a treatment. Recent court cases, such as US vs Caronia, have also changed the US FDA perspective on how products must be marketed in light of the constitutional free speech as it applies to commercial transactions related to health products. All these changes directly affect the regulatory requirements for approved/cleared products and those seeking the same by FDA. Simply, if the labeling and claims in a product are not supported by scientific and clinical data they will not be approved. Many ideas on what is next in a company’s pipeline come from what marketing observes in the field. What is the trend in healthcare? What isn’t done by the competition that I can do? These questions will always need to be benchmarked with what is possible from a regulatory perspective. Because of this, marketing must see regulatory as the partnering function to bring early in the product lifecycle. By knowing the regulatory agency’s thinking, which is something RA brings to table, marketing will be able to develop the most efficient strategy that considers every regulation hurdle early in the process. The approach is key to the management of expectations and the achievement of realistic results.

LISA GRANEY: It is a love/hate relationship! Marketing tends to view RA as an obstacle in being able to speak freely and creatively, especially regarding competitors and their claims. At other times, they like when regulatory can help craft claims and statements that can be a competitive advantage. They also appreciate it when RA can inform regulators about competitors’ claims


What improvements could be made in communications between regulatory and marketing that would help in more effective marketing and raise fewer red flags with the FDA?

GARY BARRETT: Both sides need to understand the others’ perspectives. Discussions and dispassionate argument significantly before deadlines is essential.

ROBERT GUZMAN: In a phrase, “bring them early in the process.” My experience and that of many of my peers is that the regulatory function is not brought into the picture early enough. Sometimes when we are called in, many executive decisions, financial projections and even executive commitments have been made. Then the company faces an unexpected surprise when regulatory issues surface. We end up adjusting the landscape to the project, instead of the project to the landscape with an adequate strategy. The RA function should not be seeing as another functional step to achieve a regulatory approval. It is a complete strategy by itself and must be taken into account as part of the major product strategy. Sometimes the strategy is laid focusing on what is necessary for testing, clinical, and other approval activities. But the strategy must also include other marketing areas, such as how off-labeling issues will be managed, speaker engagements, and claims substantiation, and where there has been a lot of governmental interest lately.

LISA GRANEY: I agree. Early planning. At the beginning of new product development projects, sales and marketing know what they want to say about the product – what they want to be able to say it does for the end user. That’s the time to craft the product statements and claims. That’s also when regulatory can tell them what evidence is needed to support those claims. Then, as part of the development project, R&D or product development can conduct the studies to generate that evidence.

ANDREW STOREY: Raising red flags is not an option and all of our collaborations are designed with compliance in mind first. It is important that commercial comes forward with good market research at an early enough time when it can be incorporated into the development program, labeling and advertising and promotional materials. This means formal governance meetings at different levels of the organization with ultimate review by senior leadership.

How can regulatory foster better two-way communication with sales?

ANDREW STOREY: Interact, attend staff meetings and sales meetings. Educate commercial teams on the regulatory process and challenges and what they can do to enhance chances for success. Bring value to the process by understanding the commercial drivers and bring forth original ideas for program optimization.

LISA GRANEY: Number 1: Have a detailed SOP for sales and marketing to review while creating materials. The SOP needs to discuss dos and don’ts (e.g., citations, quoting HCP’s or articles, rules on 510(k) statements). It should not be a policy that is vague. Rather, it should be in addition to the policy – perhaps a working instruction with examples. Training sessions are also valuable. Regulatory affairs can inform sales and marketing early and often about the FDA’s current thinking in areas of interest. Regulatory should also explain why they may say no to a particular topic, claim, or program. Our job is to make sure we are comfortable defending our advertising and promotional materials, based on our existing evidence and regulations. We should have a logical argument if the answer must be no. Usually there is a compromise that can be achieved if both sides understand the objective of the material.

ROBERT GUZMAN: True. It has to be an interactive approach. Traditionally, regulatory is a function to get answers when there is a regulatory question. I would say the approach by the RA function has to be proactive. By interacting with regulatory bodies, and benchmarking with regulatory affairs groups, and other sources, RA learns what the regulatory trends are, the agency’s thinking, and the enacted new guidance and regulations all over the world. RA must share that knowledge with sales and marketing to provide a vision of what is coming their way. RA should not wait for marketing to ask, but offer the information instead. There are many ways to do it. Regulatory updates can be disseminated by means of inter-office memos/emails, training, and internal panel discussions to provide an opportunity to discuss the impact of a determined regulatory change. By the same token, marketing and sales get a lot of field input. Sometimes, we learn of an off-labeling use because of an HCP practice that the manufacturer is unaware of. In these instances, marketing and sales must bring the information home to evaluate how this could affect the business from a regulatory compliance perspective. The RA-to-marketing/sales, or the marketing/sales-to-RA communication, must become a habit in order to be effective, and a project approach is suggested to ensure the issues are evaluated, documented and made actionable.

GARY BARRETT: I would sum up this way. We need discussion and an understanding of perspectives. Too often each discipline is demonized by the other, and RA becomes an impediment to sales and sales becomes a danger to compliance. Rational discussion and education on each other’s roles is a good start.

How can you improve sales reps’ understanding and communication of regulations?

GARY BARRETT: Training on the regulations and implications. Make the sales groups intrinsic to the regulatory process.

ROBERT GUZMAN: Yes. The best approach is training and active interaction. We cannot leave training alone, as it can easily become a paper exercise. To create a culture around the intended result, we need to have an interaction with all the individuals that we want to influence. Equally important, we need a steward who is savvy in the subject or an expert. Someone who understands and rationalizes the sentiment behind every regulation related to marketing-approved products. Sales personnel have in their DNA to ask relevant questions and volumes of it. If the trainer is not able to answer these concerns we will end up with bad practices in the field that can get the organization in trouble. We need to spend the time to improve the overall understanding of the subject by all functions. Only this way can we improve the culture to one of compliance and excellence.

LISA GRANEY: I think it is a matter of keeping the message clear. Sales reps have such a different job to do that trying to explain every detail would be confusing. Attending sales meetings, getting to know the reps, and providing key talking points will help them engage and remember.

ANDREW STOREY: It really needs to be through a thorough and standardized program that is highly efficient in delivery and effective in outcomes. E-learning is great for the large numbers but personal delivery of training information is highly valuable, due to its interactive nature.

How have you measured regulatory success in your company?

ANDREW STOREY: We have an extensive goal-setting process and results are measured by a multifunctional group of senior leaders.

GARY BARRETT: Approvals linked to specifically associated sales. Compliance goals.

ROBERT GUZMAN: There are tangible and intangible ways that reflect regulatory mindset evolution in a company. Those that are tangible rely on metrics presented in management meetings, where days to approval or clearance are discussed. These discussions look for the material factors that delay each individual approval and how they can be reduced or eliminate risk the next time a product application is submitted. We show the charts based on historical data through years and within the current year. Regulatory work directed to sustaining engineering projects is also tracked for improvement. This is the business aspect of regulatory. However, the best measure is the intangible one. When regulatory has been a regular contributor to each strategic and key tactical meeting, or included by other function management in relevant communications, that is a sign positive cultural change where regulatory is considered a part of the process and not a constraint. I have also experienced increase in participation by other functions when they are made part of the regulatory discussion. Some good examples have been the function request to be part of an FDA inspection as main support, when invited to Type B meetings at the FDA office, or Type B meetings on-site debriefs after meeting with the agency.

LISA GRANEY: I have not formally defined what regulatory success is and measured it. What I have observed is reduction in review time due to fewer regulatory errors, early and often engagement of my regulatory staff occurring with great frequency, and project plan line items for claim support discussions.


How early should regulatory be involved in the marketing/sales process, and to what extent?

LISA GRANEY: Again early in the process, when messages are being crafted, will help a great deal to improve the efficiency of reviews of collateral. Understanding the entire campaign and the key messages is critical. Even if this is so early that the key messages haven’t been defined fully, regulatory might be able to suggest that a particular message is easier to support than another, or evidence exists for one but not for another. It’s informal at this point, and regulatory must have an open mind and listen.

ANDREW STOREY: Absolutely. Right from the beginning. The real question should be “How soon should commercial get involved in the drug development process?” And the answer to that question varies from company to company and product to product, but in general, the earlier the better. Commercial input into Phase II study designs are critical for obtaining the most valuable commercial asset upon approval.

ROBERT GUZMAN: Yes. The earlier the better, because only RA will know when their expertise must be required. We cannot leave this decision to executives that presumably have never worked in RA, as only the expert knows when their expertise is necessary. However, a safe approach may be to bring in RA as soon as we start discussing claims and the indication for the product. It is in this phase where we know what testing is required by regulation and the required regulatory submission (e.g. NDA, BLA, PMA, 510k, Orphan Status, HDE). Also, the development of claims presents its own challenges, as a simple deletion or addition of a word may have a serious impact on the regulatory submission or prescription for the product. These changes could represent millions of dollars in product launch strategy due to additional clinical trials or testing if not carefully evaluated.

GARY BARRETT: Cost is indeed a major factor. Regulatory submissions are dictated by what sales and marketing wish to sell. The process of feasibility should include a consideration or market potential in direct comparison to the costs of registration. For instance, a simple registration of a device changes significantly depending on the desired claims. If sales/marketing wishes to aim for a pediatric market, the difficulty of registration changes dramatically. It is important that all groups involved are aware of the implications of the claims matrix.

How can regulatory help ensure that launches are planned and timed to allow for proper regulatory review, so that changes can be made in sufficient time?

GARY BARRETT: The design process needs to include a consideration of all aspects of product development. Regulatory is only a part of the process, research and development, sales and marketing, quality, etc. should all be considered and factored in to the process.

ANDREW STOREY: Right. It is a company-wide effort to ensure that launches occur with success. It requires full brand team support with strong project leadership. Regulatory needs to ensure that they have the right people with the right talent on the program.

LISA GRANEY: One: setting up a claim support process with sales and marketing; Two: being highly engaged in the early planning process, Three: knowing when major product launches, academy meetings, and other critical opportunities to the business are occurring, so that they can block and prioritize time for reviews in the weeks leading up to the meetings.

ROBERT GUZMAN: Most regulatory submission processes have a statutory cycle or impose a response time by the regulatory agency to the applicant. For example, a 510k for medical devices has a 90-day period for the FDA to provide clearance. However, the cycle may be interrupted when the agency comes with questions regarding the submission. When there is not an established cycle, the regulatory agency may be able to provide an answer on how long some processes may typically take. The RA function may be able to provide time input to the project by communicating to the agency continuously. We have what is called pre-meetings. These are meetings with FDA before the submission of an IND, BLA, PMA, and/or 510k to understand the expectations and what would be necessary for the future filing. These meetings may not be limited to RA, and other key functions could be invited. Certainly, these meetings are a forum to discuss approval timeliness and the minutes can be shared with management once back in the office. The timelines discussed with FDA must be incorporated into the project management plan.

What does regulatory want sales to know with respect to product information that may not be off-label and how that can be communicated?

LISA GRANEY: When in doubt, call RA before communicating to any external party.

GARY BARRETT: Regulatory wants sales and marketing to know that we are on their side! We are just providing a feedback service on the regulations that, if broken, have huge penalties. Ultimately we are on the same side and want to get product out in the market in the best way possible.

ROBERT GUZMAN: It must be on the label in order to be compliant. There is no way around that. Arguably, some school of thought may support that so long you have clinical or scientific data to support the claim it is reasonable. But the strict meaning for off-labeling is that it has not been approved/cleared by the FDA for the subject use. Having some scientific or clinical data does not satisfy the agency’s standard for safety and effectiveness, as it will be necessary to have valid statistical studies to meet this standard. This sometimes involves hundreds of individuals and not a handful of results collected in a white paper or article, which on some occasions is the proof obtained to support the off-labeling. Also, it is important for sales to not be involved in an HCP decision regarding off-labeling. If aware of this activity, you must notify your organization’s compliance officer to ensure this is handled properly. Since off-labeling directly affects Medicare and Medicaid, the DOJ and its states’ counterparts have been involved in the investigation of off-labeling issues. Cases like US vs Caronia may present an alternative to off-labeling, but this is considered a very high-risk practice by any company and are by no means recommended. The DOJ has changed its approach since US vs Caronia to one of where the necessary evidence to build a case has been significantly increased. This in turn ensures the effective prosecution of off-labeling practices in any court of law.

Can you relate any incidents in which coordination between marketing/sales and regulatory were well-handled?

ANDREW STOREY: Examples of successful coordination at AbbVie include strong asset teams, labeling review committees and submission planning. It is important to identify all the key items required for a successful launch and to rank them in terms of priority and probability of success so all groups are working from the same playbook. We have had some great success of late in working together to come up with very creative and intelligent labeling material that meets the needs of the healthcare professional, the health authority and the commercial drivers.

GARY BARRETT: This is always a challenge and is the responsibility of all parties to try and understand the others’ perspective. Off-label protection is the responsibility of all groups and can only be achieved when there is mutual cooperation. I have seen it work well and go terribly wrong. When it works it is a seamless early discussion with clear guidelines and mutual, if grudging, agreements. When it goes badly, it can always be traced to poor communication and/or intransigence.

LISA GRANEY: An orthopedic device was being overhauled in a two-year project to regain the market leadership in that category. The “new and improved” device had all the bells and whistles. Regulatory Affairs fully participated in the development project, all team meetings, and, as part of the project, the marketing team met with the regulatory representative regularly to discuss the product launch messaging. As a result, the product claims were documented, along with the evidence to support. At the time of launch, this reduced collateral review time by more than 50%, since review consisted of verifying that the collateral used the verbiage was documented.

ROBERT GUZMAN: Many times, the exercise of adding a claim or to clear a new 510k device becomes a direct interaction between marketing and RA for new claims in the indication. Once agreed, then R&D testing follows in the strategy. I have had the opportunity of working on many of these scenarios in my career. They are very dynamic. Basically, we hear from the market what they want. Then, we look into our portfolio for what products could satisfy that demand if improved. The improvement could be the addition of a coating to protect against certain disease, or a lubricant to ease insertion, or any other physical characteristic that would improve HCP dexterousness, or reduce patient pain. Since the subject device has a previous clearance, the marketing/ RA discussion is centered on how the new clearance must be in light of the added attribute requested by marketing. The discussion is around clinical and testing data necessary to support a specific claim.

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