Medical Device Link.

Originally Published IVD Technology June 2003

IN PERSON

An office devoted to the improvement of IVD regulatory processes helps IVD manufacturers meet FDA requirements with greater ease.

Steven Gutman, MD, is director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the Center for Devices and Radiological Health. He can be contacted at sig@cdrh.fda.gov.

In an effort to unite a previously disjointed system of regulating IVDs, an office has been established within FDA to tend to the unique regulatory needs of the IVD industry. Less than one year after the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) opened its doors, plans have been put in place for revamping the way in which IVD regulation has been viewed by the agency up until this point. Industry has been encouraged to play a central role in this transformation. To reveal what changes lie ahead for the IVD regulatory process, IVD Technology editor Richard Park spoke with Steven Gutman, MD, director of OIVD. In this interview, Gutman talks about the reasoning behind the establishment of OIVD, the goals of the office, and the importance of industry's role in attaining these goals.

IVD Technology: Please describe the history of OIVD.

Steven Gutman: In early 2002, Lillian Gill, the associate director for science at FDA's Center for Devices and Radiological Health (CDRH) put together a group of people consisting of members from all of the offices in the center who were interested in IVDs. That group was charged with developing a plan to apply a total product life cycle (TPLC) approach to the regulation of IVDs.

One early idea for how to create a TPLC framework was to dramatically change the structure of the way IVDs were regulated to allow for TPLC to occur geographically as well as intellectually.

This proposal involved taking the disparate elements of IVD regulation and putting them into a single organizational unit, a new office. That idea, which was put on the table early in the process of brainstorming, was revisited repeatedly and won out against other ideas for how to implement a TPLC for IVDs.

Last summer, both a proposed organization and an internal business plan were created for the office. The office was born on November 17, 2002.

TPLC is the central concept around which the office was based; it is the heart and soul of OIVD.

Please give a brief explanation of what TPLC is.

Total product life cycle is the notion that the best regulation is regulation that considers the big picture. In other words, FDA should be concerned with products from cradle to grave. FDA should be interested in a product from its feasibility study, when it is just a twinkle in the eye of its investigators and investors; through its development, premarket review, production and marketing; to its final end when its technology becomes obsolete and is replaced by new techniques.

Beyond premarket review and manufacturing, by implementing TPLC we would take an interest in how a device really works when it enters the marketplace, so postmarket surveillance becomes critical. And then, as the technology becomes obsolete and recycled into new technologies, FDA would be more active and recycle the knowledge gained from the original device. FDA would take that knowledge and apply it to the regulatory pattern for the children and grandchildren of each device. The TPLC concept is the notion that something can be extracted and used over the course of the life of a product and its successive models. We decided that it is very artificial to chop regulation into little premarket and postmarket pieces.

You've said that there are going to be three divisions at OIVD. What are those divisions going to be?

One is chemistry toxicology; the second is hematology, pathology, immunology, and molecular diagnostics; and the third is microbiology.

How did you select these three to be the divisions of OIVD?

Historically, they have been product lines that work well together.

What are OIVD's primary goals?

Our mission is to bring TPLC to life. We intend to better integrate the different IVD regulatory programs into a unit that allows one-stop shopping, a sharing of knowledge, and a refined regulatory approach.

Our goals encompass numerous mandates, including that we be least burdensome, and that we find creative ways to protect and promote public health through our regulation of IVDs. The general concept of protecting and promoting public health is pivotal to the thinking that drives me.

A Separate Space for IVDs

Why did CDRH decide to establish OIVD?

The regulatory questions applied to IVDs have a unique and common theme. When considering feasibility studies, premarket review, quality systems, compliance, good manufacturing concerns, or postmarket assessments, IVD criteria and issues are focused on common principles: device accuracy, precision, specificity, and sensitivity. There's a common motif in the regulatory themes that apply to our products.

Among medical devices, IVDs are second to none in terms of rapid, wide-ranging innovation. We need to rethink the way we review these products so that we can provide the appropriate balance of caution and open-mindedness, and that we are both protecting public health and promoting public health by releasing new high-quality products quickly.

Our regulatory staff is quite talented and versatile, and IVDs are unique enough and have a strong enough regulatory backbone that they're in need of a separate office.

The primary goals of OIVD are quite transparent and they're clothed in the concepts of the TPLC. They're also embodied in the notion that, as hard as we work and as collaborative as we are in our regulating across different organizational units, there are differences in culture, work priorities, and work mechanisms across these units. To maximize the impact of the TPLC, establishing a single office for multiregulatory purposes is a good first step.

We intend to provide a new one-stop-shopping office.

Does the creation of an FDA office solely dedicated to IVDs indicate the agency's realization of the importance of IVDs, and, if so, how did FDA come to this realization?

Well, I'm not sure that they've only recently come to this realization. Early in the history of device regulation, FDA considered IVDs to be unique and they were regulated separately from other medical devices. So we're actually returning to the past.

Most astute regulators and scientists appreciate that it's not patient contact, but the impact of a device that makes it safe and effective, and makes it either high or low risk. The impact of an IVD lies in the information it provides from the results of the test it performs, and by the repercussions of a true versus a false positive and a true versus a false negative.

The creation of the IVD office indicates that FDA understands the importance of IVDs, but I don't think that it is a new realization.

The agency's decision to open a separate office probably had more to do with the exploding technology for IVDs, the commonality of the regulatory questions, and the talent and multitasking ability of our staff, rather than a relative assessment of the importance of IVDs in comparison with other medical devices.

Impact on Industry

How will the establishment of OIVD benefit IVD manufacturers?

It will create increased clarity and transparency in both regulatory requirements and processes. The office will produce more-unified and faster responses from FDA on regulatory matters. It will lead to better-informed regulatory policy decision making; and I hope that it will achieve these goals through the maintenance of very strong communication with outside stakeholders. This communication includes productive dialogues with both industry and professional groups, along with our efforts to be creative and proactive in our interactions with industry.

How will IVD regulatory activities be different now that OIVD has been established?

There will not be big immediate changes for manufacturers right now. IVD manufacturers are still required to provide premarket submissions as appropriate, either 510(k)s or PMAs, or in rare cases, IDEs or HDEs. Manufacturers must still follow the quality system regulations and ensure that their products comply with those regulations. They are still required to use the med watch system and medical device reporting when they run into trouble.

The immediate impact will be administrative one-stop shopping and improved dialogue and communication, but it won't be startling changes in work product. Hopefully, we'll be faster, more efficient, and clearer at what we do, but we won't be doing anything differently, at least in the short term.

I think in the medium and long term, we will rethink the context of the rules that we play the game by. We would like to reassess how we manage our work processes, whether there are better ways of doing business, and whether we could collaborate with either professional or industry groups to promote both the rapid transfer of technology into the medical marketplace and a clear understanding of how technology is working in the marketplace.

How will OIVD expedite the review of IVDs?

We are trying to standardize our review approach, ensure that our review requirements are clearly communicated, and look for administrative economies in the way we do business. I believe that having all relevant expertise under one roof will speed up a wide variety of review and regulatory processes.

What type of new compliance measures do you plan to put in place at OIVD?

We'd like to do a better job of communicating regulatory compliance requirements, so we would like to improve industry's understanding of our expectations.

We're very eager to be friendly and work with companies. We intend, when necessary, to use compliance regulatory tools, so we don't plan to abandon the tools that work well. We are striving for a new regulatory mix, but we intend to hold on to well-established regulatory patterns.

What other effects will OIVD have on the IVD industry?

The new office presents an opportunity for the IVD industry to work creatively to provide and protect public health and ensure that appropriate levels of data thresholds and appropriate labeling are in place.

I've been impressed with the fact that industry representatives have already stepped up to the plate and presented us with creative ideas. We request that when people approach us with their ideas, the ideas should be credible. FDA is looking for ideas that are realistic in the sense that they meet our mandate of protecting and promoting public health.

Regulatory options should be grounded in good science, they should be transparent, and they should be balanced to meet the needs of both the manufacturers being regulated and the laboratory users who purchase regulated products.

Ideally, the endpoint of our work is to ensure that laboratory tests meet appropriate data and labeling thresholds but enter the market in a timely fashion in order to ensure continuous improvement in laboratory medicine. The litmus test for any proposed change to a regulatory path or process is how well it serves this delicate balance.

Recent Developments

Have you and others at OIVD made any progress toward rethinking work processes there?

We are still in the process of recruiting leaders for the office. We are making some small incremental changes. We established the OIVD Web page, www.fda.gov/cdrh/oivd, to provide information to our stakeholders and we are doing a lot of thinking. We have invited both professional groups and industry groups to brainstorm with us and offer input. It's not too late, or too early, to put ideas on the table.

Granted, OIVD has only been in place since November, but have you seen an improvement in the efficiency of IVD reviews?

I have. Our times for both review and compliance responses have been faster. We're having more interactive exchanges with the folks that we regulate. We're using real-time interaction for compliance assessments to see if we can head off problems before they become full compliance problems, by collaborating with companies. We've been very impressed with how collaborative and interested companies have been, either in doing the right things, or in keeping us off their backs. So I think we're starting to see changes.

I've seen cultural changes, in that there has never been a stronger connection between review and compliance workers, in the 10 years I've been here. We, in both the review and compliance staff, have never received such immediate access to postmarket surveillance information. In a short period of time, we've been able to access information from the field that, previously, had always been filtered or kept from us.

What other aspects of OIVD are still in development and which are priority areas that must be completed immediately?

There are unique product issues that transcend the TPLC. We have real challenges in terms of administration and keeping abreast of new molecular diagnostic technology, particularly microarrays. We have a daunting agenda in terms of finding a way for FDA to play a greater role in regulation of some of the genetic tests and defining what that role might or might not be. Nowadays, we also have to make sure that we deal with both bioterrorism threat diagnostics and diagnostics for rapidly emerging infectious diseases very rapidly.

What action improvements does OIVD plan to make in the future?

We will continue to refine and improve the way we promulgate guidances and expectations. We'd like to utilize real-time processes more broadly so we can resolve scientific issues more quickly, in conjunction with industry. We'd like to improve transparency. There has been discussion about standardizing our review memos and actually posting them so that people will have examples of paths to follow, and they won't have to go through FOI (Freedom of Information) to determine which data sets they'll need to present to us.

We're looking for ways to better educate ourselves about quality system processes and to pass our technical experience and knowledge on to people who are involved in field work.

We're looking for a better way to accumulate postmarket data. And, to that end, we're working with members of the Office of Surveillance and Biometrics, to expand the Med Sun pilot to include labs in a new project called Lab Sun.

Industry Influence

What sort of input would OIVD like to get from IVD manufacturers?

The most important thing that IVD manufacturers can let us know is how they're faring on a day-to-day basis and what process improvements we can make. How has their experience been when they're interacting with us during premarket submissions, compliance activities, and postmarket surveillance? It would be helpful if IVD manufacturers would indicate what's working and what's not working.

We have an obligation to meet the spirit of the regulations and the law, so we're not entirely malleable, but we are interested in impressions and feedback. So, if manufacturers let us know whether we are doing our job quickly and correctly, we are eager to obtain their perspectives. While what we might think and what the regulated parties might think might not always be the same, dialogue about these issues will almost always be helpful to both sides.

I hope that when industry and OIVD disagree, industry understands that it has options for disagreeing with us. My request would be for manufacturers to think in terms of TPLC, knowledge management, and how can we be partners in this deal.

Has OIVD set up any sort of mechanism, formal or informal, that allows IVD manufacturers and professional groups and associations to provide you with feedback?

We meet both with industry and professional groups three to four times a year, under the auspices of roundtables.

These are not FDA meetings; they are actually industry meetings. And people who are interested in participating should contact one of the big industry groups and join that group. All of the key laboratory professional societies are represented at our professional roundtables. The meetings are sponsored by those professional societies. We participate in those meetings as an opportunity to exchange informal dialogue and engage in brainstorming and collaborative work.

However, IVD manufacturers don't have to participate in those meetings to contact FDA. In fact, private parties, single manufacturers, a single group of scientists, a single regulatory affairs person can all offer input. If someone has a great idea, the one thing they should do is call someone here in the office and talk to them about it.

Steven Gutman, MD, is director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the Center for Devices and Radiological Health. He can be contacted at sig@cdrh.fda.gov.

Copyright ©2003 IVD Technology