Rethinking the Role of Clinical Affairs (Posted on 04/09/2013)
By Joel Batts, SANUWAVE Health
Historically, the nature and function of clinical affairs within the orthopaedic device industry have been understood from a perspective of premarket need. Ask a device firm’s leadership why a clinical affairs team is part of the company infrastructure, and the response will likely make reference to securing key product approvals. This perspective is understandable. The long, arduous road of conducting clinical trials as part of the Investigational Device Exemption (IDE), Premarket Approval (PMA) regulatory pathway is of no small consequence, at times determining whether a firm will sink or swim. It is not surprising, then, that “clinical” has become virtually synonymous with IDE. Yet, in much the same way as individual cells work together to make an organism what it is, clinical affairs should be viewed as one of many multi-related, multi-obligated teams that collectively define the organization’s life.
At first glance, use of the organism analogy may seem like Organizational Management 101. Assemble cross-functional teams—check. Make sure clinical affairs has signed off on the design control documentation—check. Regroup as needed to determine what, if anything, is necessary from clinical to secure approval or keep a product on the market—check. Such checklists are good and necessary. However, if the last five years (and counting) of tectonic shifts in the orthopaedic industry have taught anything, it is that gaining crystal clarity regarding the nature and function of roles is a healthy thing to do prior to executing within those respective roles.
In light of this background, the following perspective seeks to be a starting point for discussion on the nature and function of clinical affairs. The goal is to gain a more expansive view than the traditional IDE paradigm allows so that substantially greater benefit is realized in the overall life of a medical device firm.
1. Science is the nature of clinical affairs
Consider these terms: hypothesis, randomization, minimization of bias, statistical analysis plan, equipoise. Clinical affairs is heavily laden with such language because its nature is scientific. If product development can be said to “encode” the intended behavior of a device into its design, clinical affairs can be seen as the “decoder” of how it actually behaves in patients. The extent of overlap between the encoded intended behavior and decoded observed behavior can be measured in terms of efficacy (controlled trial) or effectiveness (observed, real-world use). Many implications emerge from this perspective, three of which can be briefly described here.
First, because this scientific nature involves quantifying the extent of desired overlap, as well as the methods used to measure that quantity, the framework for a clinical study actually begins to take shape during device conception. Put this way, it is immediately apparent that clinical affairs should be integrated in the nascent stages of product development regardless of the regulatory pathway to approval. While the eventual decision may well be that the device does not require a full-fledged clinical trial, final design review is much too late in the game for sufficient consideration.
One of the hallmarks of sound science is the selection of variables that can be accurately measured. A second implication of having a scientific nature, therefore, is the need for clear, consistent communication across the organization as to what a particular study is and is not measuring. Clinical affairs professionals, this author included, should strive to promote ubiquitous inter-departmental understanding of the main features of specific trial protocols. In doing so, the entire organization will anticipate the same deliverable which, when derived from the data, will be on target with the pre-defined questions the trial is attempting to answer.
Finally, the scientific nature of clinical affairs necessitates taking a long-term view with respect to firmly characterizing product performance. Comparative Effectiveness Research (CER) grew out of the realization that short-term, controlled clinical trials have limitations in making real-world conclusions precisely because they are short-term and controlled. Device registries and other tools have surveillance capabilities to make real-world observations, but conclusions can take several thousands of patients over several years. Nevertheless, one of the tectonic shifts in the last five years was the European Union’s Medical Device Directive (MDD) essentially mandating a long-term view. Using the language of product “life cycle,” the MDD clarified that “clinical evaluation is an ongoing process conducted throughout the life cycle of a medical device. It is first performed during the conformity assessment process leading to the marketing of a medical device and then repeated periodically as new clinical safety and performance information about the device is obtained during its use.”
2. Construction, execution and results dissemination of trials are the function of clinical affairs
Based on the view that science is the nature of clinical affairs, it is only a short distance to see its function—the construction, execution and results dissemination of clinical trials. The singular form of the word “function” is used to imply continuity and dependency, or put negatively, to communicate that dysfunction results when construction, execution and results dissemination are performed independently.
A helpful analogy for illustrating clinical affairs function is the design control process in product development as shown in Exhibit 1.
Exhibit 1: The Design Control Process in Product Development
The point of this analogy is not to present clinical trials as necessarily the same in complexity or workflow scope as that required for device development. Rather, the analogy aims to make the function of clinical affairs clearer by relating it to the more tangible science of creating a medical device. In so doing, the engine of clinical function—investigators, coordinators and clinical affairs team—can continually assess improved ways for optimizing output, much the same as engineers, drafters and prototype makers evaluate better ways of optimizing device characteristics.
Although not nearly exhaustive, the above discussion attempts to show that an IDE-only paradigm is inadequate if a firm is to reap the full benefit of investing in a clinical affairs team. If the nature of clinical affairs is science and its function is construction, execution and results dissemination of clinical trials, a commensurately broad value proposition is in order. Clinical affairs leadership should establish such a proposition by thoroughly understanding the objectives of all other teams within the firm, and then defining as internal customers, those teams whose objectives will be served by clinical data. The value proposition should be formally written so that clinical team members perform in the context of obligation to internal customers, while the internal customers themselves gain progressively broader scope regarding the value they are being provided. This initial step of establishing a value proposition aims to culminate in firm-wide desire for maximizing the range of benefits derived from a clinical affairs team.
Joel Batts joined SANUWAVE in October 2011 to lead the dermaPACE clinical study. He previously served as Senior Director of Clinical Affairs at Wright Medical Technology where his focus was orthopaedic reconstructive products, foot and ankle products and wound therapy. He has a Bachelor of Science in Exercise Physiology from the University of Florida and is finishing a master’s in bioethics and health policy at Loyola University Chicago’s Stritch School of Medicine. Contact Joel at firstname.lastname@example.org.
This article also appeared in BONEZONE®, March 2013.
Companies Receiving First Orthopaedic 510(k) Clearances in 2Q/3Q12 (Posted on 09/15/2012)
Dallas, Texas, USA
Matisse Anterior Cervical Interbody Fusion Cage, K121569
Kalamazoo, Michican, USA
Erisma-LP Pedicle Fixation System, K120469
San Diego, California, USA
IM Nail System, K102577
- High Strength 6-4 Titanium Alloy to ASTM F 136; intended for tibiotalocalcaneal arthrodesis, stabilization of hindfoot and ankle including transverse tarsal joints coupling mid-foot to the hindfoot
Washington, D.C., USA
2GC Hip/Knee Modular Spacer, K112470
- Both devices made from fully formed polymethylmethacrylate, radiopaque, contain gentamicin
Calypso Spinal Fixation System, K120564
Cranbury, New Jersey, USA
Seviin Reverse Shoulder, K120374
- Ti-6A1-4V alloy metaglene plate with titanium plasma spray coating, Ti-6A1-4V alloy bone screws, Co-Cr-Mo alloy glenosphere, Co-Cr-Mo alloy humeral cup and ultra high molecular weight polyethylene (UHMWPE) inlay
San Mateo, California, USA
Tempus Cervical Plate, K120515
- Company “dedicated to exploring cost-effective approaches and less-invasive surgical options that provide optimal outcomes for the surgeon and the patient.”
Daytona Beach, Florida, USA
Laminoplasty Plating System, K121276
Woodbury, Connecticut, USA
Twin Peaks Lumbar Cage, K112696
- Company focuses upon “off-patent products that have years of success in the market,” bringing them to
customers “direct and without the extra middleman costs”
Eldorado Hills, California, USA
Pedicle Screw System, K120091
Sources: FDA 510(k) Releasable Database, company press releases, web sites
Companies Receiving First Orthopaedic-related 510(k) Clearances in 1Q12 (Posted on 04/10/2012)
Complete information on these filings is found in FDA’s 510(k) Premarket Notification Database.
Las Vegas, Nevada USA
OsteoLaso Bone Void Filler, K111018
Granule and strips
· Beta-tricalcium phosphate and polyphosphate
Titanium Nailing System, K113387
· Dinamic T Humerus for proximal humeral fractures, Endovis BA Femur for lateral proximal femoral fractures, etc.
Slatington, Pennsylvania USA
R&R External Fixation System, K113106
· Aluminum, Ti6A14V alloy, stainless steel
· For use on all long bones
Lyndhurst, New Jersey USA
Patient/Technique-specific Humeral Plate, K112663
· Start-up company; management includes notable orthopaedic industry-specific experience
· Company has also designed a “crowd-funding and collaboration platform that empowers medical professionals to hatch good ideas into great products.”
Orthopaedic Implant Company
Reno, Nevada USA
Cannulated Screw/Sliding Hip Screw System, K113123
· For adult and pediatric patients as indicated for pelvic, small and long bone fracture fixation; for use in subtrochanteric, intertrochanteric and basilar neck fracture
· Company formed as a “collaboration
between practicing orthopaedic surgeons, hospital administration and orthopaedic industry insiders” to provide “high quality implants at a fraction of current costs”
Cedar Knolls, New Jersey USA
Total Hip System, K112802
CR Primary Knee System, K113122
· Founded by management team with “more than a century of experience in orthopedics”
· Company created to focus on “design of high tech orthopedic implants, manufactured with novel biomaterials, for use with navigation and robotic bone preparations”
Avondale, Arizona USA
Spinal System, K113755
· Adaptable titanium alloy fixation system designed to allow dorsal stabilization of the spine
Skeletal Design Partnership
Hambrook, Bristol UK
Foundation Spinal System, K120074
Sources: FDA 510(k) Releasable Database, information in the public domain
The View from Washington: What Device Makers need to Know about FDA\\\'s Latest Strategic Priorities and Initiatives (Posted on 07/15/2011)
Continuously hammered by Congress, news media and the international health community, the U.S. FDA has responded with a five-year plan that could have far-reaching consequences for the medical device industry.
In late April 2011, FDA Commissioner Margaret Hamburg and her staff released a 50-page report on FDA’s Strategic Priorities, 2011-2015: Responding to the Public Health Challenges of the 21st Century. The report outlines five goals and accompanying actions that cut across all types of FDA-regulated products. In addition, the report sets two
more goals specifically targeted to the medical device industry.
FDA’s five cross-cutting priorities over the next five years include:
* Advancing regulatory science and innovation
* Strengthening the safety and integrity of the global supply chain
* Strengthening compliance and enforcement activities to support public health
* Addressing the unmet public health needs of special populations, and
* Advancing medical countermeasures and emergency preparedness
The theme running throughout the entire strategic plan is the agency’s renewed focus on regulatory science and innovation. “Science underlies everything we do at this agency, and to serve the public health we must have the capacity to effectively oversee the translation of breakthrough discoveries in science into innovative, safe and effective products and life-saving therapies for the people who need them most,” the Commissioner says.
Let’s examine where these priorities intersect the interests of the device industry.
Priority #1: Advance Regulatory Science and Innovation
Under its first priority, FDA wants to facilitate the development of new biomedical products and emerging technologies. The agency plans to become more engaged in what it calls “mission-critical” fields of applied research, including wireless healthcare devices, nanotechnology, medical imaging, robotics and combination products. To support this goal, FDA is identifying strategies to recruit and retain top-level scientists and work more collaboratively with industry as well as other government agencies and academic institutions.
Also in support of better regulatory science, FDA wants to standardize the enormous amounts of product data it receives from industry. Now that the agency is getting more clinical data and medical device reports (MDRs) electronically, FDA believes standardized data will make its product review, approval and surveillance processes more efficient. The agency’s ultimate goal is to create a common database of harmonized information that allows its staff to compare multiple studies and reports, and query the database by specific topics. As the first step for meeting this goal, FDA is developing a clinical trials data repository.
Priority #2: Strengthen the Global Supply Chain
The agency’s second priority is particularly relevant to the device industry, in which the use of outsourced suppliers for key components and assemblies is widespread.
FDA admits that the growing challenges of globalization have far outstripped its resources for inspecting and monitoring product quality. As a result, the agency wants to shift more responsibility to industry, expecting device makers themselves to identify and control supplier risks. In addition, the agency says that it may develop new regulatory standards to encourage corporations to monitor these risks throughout the product’s entire life cycle.
Priority #3: Strengthen Compliance and Enforcement Activities
As part of its third cross-cutting priority, FDA is implementing a number of new programs designed to make its enforcement systems faster and more effective. One is establishing new deadlines for industry to respond to significant inspection findings. Another is a new process for prioritizing follow-up inspections after the agency has issued Warning Letters, classified major recalls or taken some other significant enforcement action.
FDA’s enforcement plans also include creating more vigorous alliances with global regulators and standard-setting bodies. In the next five years, FDA wants to use its network of FDA field offices, local, state and territorial regulatory authorities and foreign government officials to share more laboratory and enforcement data.
A big component of the agency’s new enforcement focus will be criminal prosecution. Used sparingly in previous administrations, FDA’s criminal enforcement program includes prison sentences, fines, restitution and forfeiture. FDA says these criminal sanctions will be highly publicized, with the intention of informing consumers and making an example of bad-acting individuals and corporations to deter future criminal behavior.
Priority #4: Address Health Needs of Special Populations
In discussing its fourth priority, FDA says there are many vulnerable and underserved populations that deserve special attention from regulators and the public health community. It especially singles out women, minorities and children as underrepresented in clinical trials.
The agency expresses concern that medical devices often are not tested in or sized for a relevant pediatric population. It also would like to see the industry make additional efforts to understand the long-term safety of devices used chronically in children. Over the next five years, FDA plans to expand its research efforts, grant and communication programs and international collaborative efforts to reach out to these special populations and encourage industry to do the same.
Priority #5: Advance Medical Counter-measures
Regarding its fifth strategic priority, FDA admits the U.S. still does not have the range of medical countermeasures (MCMs) needed to effectively respond to a chemical, biological, radiological or nuclear attack or infectious disease outbreak. The agency says there are not enough FDA-approved MCMs such as vaccines, diagnostic tests and personal protective equipment to respond to these types of public health emergencies.
Going forward, FDA is developing an MCM action plan with three main efforts:
* Upgrade the MCM review and approval process by building multidisciplinary public health and security action teams.
* Advance regulatory science for MCM development and evaluation through internal and collaborative external research. FDA’s goal is to identify situations where the application of new
science could simplify or speed product development and/or the regulatory process.
* Optimize and, if needed, overhaul the legal, regulatory and policy framework for effectively responding to public health emergencies.
Industry Specific Priority: Advance Medical Device Safety and Effectiveness
A summary of FDA’s long-term objectives for medical devices appears in Exhibit 1, below.
SUMMARY OF FDA’S LONG-TERM OBJECTIVES FOR MEDICAL DEVICES
Fully implement a total product life-cycle approach that enables well-supported regulatory decisions at any stage of a device's life cycle.
Enhance and integrate premarket, postmarket and compliance information and functions by taking actions to:
* Strengthen Premarket Review
* Aligh scientific resources throughout the program
* Optimize data collection and analysis
* Address challenges associated with globalization
* Enhance compliance capability
Proactively facilitate innovation and address public health needs
* Foster development of innovative medical devices
* Develop a personalized medicine program
Beyond the five strategic priorities that impact all FDA-regulated products, the new FDA report specifically cites two more focal points for its device program:
* Improving the quality, consistency and predictability of regulatory decision-making, and
* Facilitating medical device innovation
The agency plans to take a total product life cycle approach to regulating the medical device industry – from development and design through obsolescence. As part of its effort to strengthen its device premarket review programs, FDA completed a comprehensive assessment of the 510(k) program and its use of science in regulatory decision-making.
In August 2010, the agency released its findings and recommendations in two reports, “CDRH Preliminary Internal Evaluations (Volumes I and II).” FDA solicited feedback on the reports at two public meetings, three town hall meetings, three open public dockets and several meetings with individual stakeholders.
Based upon feedback from the device industry and the concerns it expressed about being able to innovate under new rules, FDA announced in May 2011 it would:
* Publish guidance for industry to clarify when clinical data should be
submitted to increase predictability and transparency
* Develop a network of external experts who can use their knowledge and experience to help the agency address important scientific issues regarding new medical device technologies
* Establish a new Center Science Council of senior FDA experts within CDRH to foster more timely and consistent science-based decision making
While encouraging innovation, FDA says it must not stray from its equally important mission of ensuring safe devices. Accordingly, the agency plans to:
* Establish a public database of important device information, such as
labeling and summaries of the basis for FDA’s decisions to clear specific devices
* Require device manufacturers to provide a brief description of scientific information regarding known safety and effectiveness issues for select high-risk devices
Meanwhile, the device industry awaits the recommendations from the Institute of Medicine (IOM), which is conducting an independent evaluation of the 510(k) program. Published reports from April 2011 show that the IOM has completed its internal review and is now soliciting comments from the industry. The IOM report is expected later this summer, while the entire FDA five-year strategic report can be accessed now from the agency’s website.
Responding to These Initiatives: Suggestions for Industry
What does FDA’s five-year plan mean to the medical device industry – now and in the future? I would suggest companies use this time – while the agency is deciding how best to meet these priorities – to “get ahead of the curve.” We all know that change at FDA can be slow, but as a 22-year veteran of the agency, I am confident in saying that many of these changes are inevitable.
I suggest you gather the highest levels of your management together and conduct a thorough and honest appraisal of your following activities.
1. Supplier Selection and Control
FDA holds management, not the quality assurance department, responsible when outsourcing decisions go bad. Anything and everything can be outsourced, except responsibility. Review your policies, Standard Operating Procedures and even your corporate culture to ensure that you have integrated supplier selection and control throughout your quality program.
Don’t just periodically audit your suppliers, monitor them continuously – just as you would any other critical manufacturing process.
All too often, when a company outsources a process or a component, it reduces its quality assurance staff, assuming that the supplier will handle those responsibilities. But in reality, the more you outsource, the more you need a vigorous and vigilant
quality assurance department. Monitoring an outsourced operation can be far more difficult and time-consuming than monitoring any internal operation.
2. Inspection Preparedness and Response
Understand that there will be heightened oversight of your operations – worldwide. The most obvious evidence of this oversight will be inspections, not all of them directly conducted by FDA. There will be better local, national and international coordination of inspection strategies and more sharing of inspection results. You’ll see more “corporate Initiatives,” meaning that FDA will undertake coordinated inspections of multiple manufacturing sites, looking for common quality control problems that may cut across diverse product lines.
One of the tools to use to improve your inspection readiness is FDA’s own publicly available “Investigations Operations Manual,” a collection of agency policies, guidelines and checklists used by FDA field investigators. With the Manual in mind, EduQuest has written an Advisory on “Using FDA’s Own Playbook to Prepare for Your Next Inspection,” available by contacting me via email.
FDA will continue to place a high priority on documentation. The agency’s unstated motto is, “If it isn’t documented, it isn’t done.” So document everything associated with your product decisions. Have those documents easily accessible for your own staff and for FDA inspectors.
In the past 30 years, I’ve audited literally hundreds of device design, manufacturing and distribution facilities around the world and found that documentation is universally poor. Everyone loses design records and other key documents, and just about everyone fails to record (i.e, document) key product decisions and justifications. But understand that poor documentation is low-hanging fruit for agency inspectors. It also makes for embarrassing and share-price deflating fodder for the news media when the information gets out (as it inevitably does).
4. Risk Management of Your Product’s Life Cycle
Understand the agency’s expectations for risk management and incorporate them in all of your decisions – business as well as scientific. Factor risk management into the very initial stages of your product design and carry it through to postmarket surveillance. Expect that MDRs, recalls, and device advertising will attract more agency attention and enforcement resources.
5. New Product Development and Scientific Support
Monitor FDA’s actions on the 510(k) program closely, including its response when the new IOM report is released. Make your voice heard whenever possible. But be prepared that most likely, as a tradeoff for more expeditious agency reviews, you will need to share with the agency and eventually the public more scientific information about your product than ever before.
Increasingly, the information you develop and share will need to be standardized. Get involved now with industry trade groups and standard-setting bodies so you can participate in the decisions and get a head-start on adapting your internal systems to the evolving standards.
If you have especially cutting-edge products or emergency medical countermeasures, look for opportunities to collaborate with the agency either directly or through third-parties such as academia. FDA wants your product to succeed, but you have to do your part in establishing and documenting solid scientific evidence of its safety and effectiveness.
FDA’s Strategic Priorities, 2011-2015: Responding to the Public Health Challenges of the 21st century. www.fda.gov/aboutfda/reportsmanualsforms/reports/ucm227527.htm
FDA’s Investigations Operations Manual. www.fda.gov/ICECI/Inspections/IOM/default.htm
Martin Browning is the President and Co-Founder of EduQuest, a global team of FDA compliance experts based near Washington, D.C. He spent 22 years with the FDA as a local, national and international expert investigator, then served as special assistant to the Associate Commissioner for Regulatory Affairs. He also was the vice chair of the agency’s Electronic Records and Signatures Working Group, which drafted the 21 CFR Part 11 regulations. Martin served as the chair of the U.S. government’s ISO 9000 committee; on the Global Harmonization Task Force, and on the committee that developed the Good Manufacturing Practice regulations for medical devices, otherwise known as the Quality System Regulation (QSR).
He is the program chairman of EduQuest’s popular training courses, including “QSR Compliance Fundamentals,” “Design Control for Medical Devices,” “FDA Auditing of Computerized Systems and Part 11” and “The CAPA Clinic: Effective CAPA Systems and Failure Investigations,” all offered globally. Details are available at www.EduQuest.net. Comments and questions about this article can be addressed to Martin Browning in care of Info@EduQuest.net.
Special thanks to Martin Heavner for his assistance in securing this article.