MD+DI Online is part of the Informa Markets Division of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC's registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 8860726.


Articles from 1995 In November

Ohmeda Explores Partnerships with Hospitals

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

Originally published November 1995

The economic pressure being exerted on hospitals by capitation and managed care is forcing a reevaluation not only of the way medical equipment is acquired, but of how it is designed and used. Some hospitals may soon begin experimenting with new cost-saving strategies, such as the use of anesthesiology machines incorporating meters to record the amount of time they are in use.

According to Don Spence, vice president of marketing at Ohmeda Medical Systems Division (Liberty Corner, NJ), which supplies the machines, the idea is not to turn anesthesiologists into clock punchers, but to gain access to information about how the technology is used. "We need data about processes from the machine so that we have a chance to improve costs and outcomes," Spence says. Thus, metered equipment would not be a product, but rather a research tool, perhaps to be applied at institutions collaborating with Ohmeda to conduct research into the practice of anesthesiology.

Such partnerships will be integral to the future of the company, he explains. For hospitals, the data generated by devices such as metered anesthesia machines should ultimately enable them to develop purchase plans that more accurately reflect the way the equipment is used. "More and more, the operating room is not a profit center but a cost center," Spence notes. "We have to move away from this idea of selling things and start selling solutions."

One implication of the changes wrought by capitation and managed care is that the traditional methods of capital acquisition - purchasing, leasing, and renting - may eventually become extinct. Instead, customers may opt to pay for equipment by the hour, in which case anesthesiologists might indeed punch a clock on their machines. Hospitals might be better served, however, if they pay for equipment on a per-procedure basis, with different procedures incurring different charges. These charges might include not only the use of the anesthesia machine, but also consumption of the anesthesia agent and some disposables. Information management systems will help to determine how these charges will be applied and how the various components will be bundled, Spence says.

Spence's proposed formula for success applies beyond the anesthesia marketplace, he says - it applies to all medical device companies. "Companies that focus solely on providing tangible products without understanding their customers' needs and processes will suffer a significant margin squeeze," he says. "In five years, some of us vendors will be here and some of us won't. We certainly hope we will be among the survivors, but getting there will require us to be flexible and offer a wide range of programs to customers."

- Greg Freiherr

(This article originally appeared in the November 1995 issue of Medical Device & Diagnostic Industry. © 1995 CanonCommunications, Inc. All rights reserved.)

Spring Release Expected for Revised GMP and Guidances

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

Originally published November 1995

Spring 1996 is now the new target date for promulgation of FDA's long-awaited revision of its good manufacturing practices (GMP) regulation, but the agency has yet to determine how and when the new GMPs will take effect. In the meantime, FDA is also turning its attention to the development of crucial guidance documents that it hopes to release shortly after publication of the final regulation.

Final work on the revised GMP regulation follows the recent meeting of the agency's GMP Advisory Committee, which gathered in Gaithersburg, MD, on September 13-14 to hear industry testimony about the agency's July draft of the regulation and to offer advice on key areas of concern to industry. The meeting was the first in three years for the nine-member committee, which had to be reconstituted after nearly being eliminated by government bureaucracy busters. Among the issues under consideration were the applicability of the GMP regulation to component manufacturers, how it should define and regulate servicing and remanufacturing operations, and whether it should be phased in or made effective all at once.

The committee was in full agreement on the issue of component manufacturers, voting nine-to-zero to recommend that the GMP regulation not be extended to apply to them. "This vote wasn't too surprising," said device industry consultant Anita Thibeault of Anita Thibeault and Associates (Rogers, AR), who is serving as one of the two industry representatives on the committee. "No one who thought about this from a purely logical standpoint would conclude that component manufacturers should be subject to the GMP regulation."

On issues related to servicing, however, the committee was divided along a number of lines. In testimony from third-party service organizations, the committee was urged to make hospital service technicians subject to the regulation in order to provide a level playing field for all servicing organizations. "The biggest question was whether this regulation should be applied to third-party servicers and hospital personnel that it didn't seem intended for, that had not previously been under the regulation, and for whom it would be an unusual burden," noted Thibeault.

While several committee members expressed the view that FDA regulation of hospital service technicians was an essential public health issue, "there was no clear-cut consensus," said Thibeault. "Other members argued that applying the regulation to hospitals and third-party servicers would burden the health-care system by forcing users to go to the original manufacturer for parts and service, thus making it more expensive for them to buy and maintain equipment than if they were able to use third-party servicers with less overhead."

Despite FDA's admission that it does not have the resources to enforce the servicing requirements in hospital and other clinical settings, in the end the committee voted five-to-four to recommend that user-facility service technicians be subject to the regulation.

On related issues regarding the responsibility of manufacturers to provide service manuals for use by third-party servicers, the panel expressed a variety of views. "FDA had proposed language requiring manufacturers to 'ensure that the device's safety and performance specifications, as set forth in service manuals or literature,' be made available to servicers," noted Thibeault. "I felt that language was too general and didn't deal with the fact that companies that make instruments often have separate technical or service manuals that include such details as schematics, board design, and circuitry - all the things that go into servicing a device. In some instances, these manuals reveal the design of the product, and that information is proprietary, intellectual property. As written, the regulation requires manufacturers to give that information away 'at a cost not to exceed the cost of preparation and distribution,' despite the protections for intellectual property provided by copyright and patent laws. I felt there needed to be a balance in FDA's approach; patient safety is the primary part of this equation, but protection of intellectual property also has to be a factor," Thibeault added.

According to Kimberly Trautman, acting chief of the Cardiovascular/Neurology Branch in the Office of Compliance of FDA's Center for Devices and Radiological Health, the agency's proposed language was not meant to apply to proprietary information, but only to such manuals as manufacturers had already released for distribution outside their companies. "The intent was to ensure that if a manufacturer was already providing information to one group of servicers, such as its hospital customers, it would also supply that same information to all other service organizations," Trautman said. In the end, the panel voted to retain FDA's proposed language, even though some committee members recommended that it be carefully scrutinized to determine exactly what it would require manufacturers to give away.

Trautman expects that revision of the new GMP regulation to meet the committee's recommendations will take several months, and that the final version will be promulgated next spring. Release of GMP-related guidance documents will take place during the months intervening between promulgation and the final date for the statute to go into effect.

"The first guidance document that FDA wants to produce is one on design control, because that area is going to be new for almost everyone," said Thibeault. Trautman confirmed that the agency's Harmonization Task Force is now working on a guidance for design control, and that a second draft - still not ready for public circulation - is expected very shortly. A second guidance on process validation is expected to be included in a horizontal guidance on validation now being prepared by European members of the task force. Other documents being planned include a guidance on human factors, which is being compiled by the device center's Office of Health Industry Programs, and a compliance guidance on software validation.

Thibeault suggested that FDA might need to issue a compliance guide on servicing for the use of agency investigators, and that industry may need additional GMP-related guidances in areas such as the handling of nonconformances, and corrective and preventive actions. "Statistical techniques might be another area of interest, since companies are having a hard time understanding what they're supposed to do in that area," she noted.

In the wake of the citizen petition submitted by the Indiana Medical Device Manufacturers Council (IMDMC) to halt FDA's use of "improper" methods in creating industry guidances, it is unclear what process the agency intends to use for soliciting comment on the planned GMP-related guidances. "At this stage, FDA would probably not put out any guidance that would affect industry in an important way without first conducting a public review," noted Thibeault.

Although the GMP Advisory Committee has in the past been called upon to assist the agency in the compilation of guidances and conduct of public hearings, Trautman doubts that it will play a major role in the development of new GMP-related guidances. Bradley Merrill Thompson, an attorney with the firm of Baker & Daniels (Indianapolis) and counsel for the IMDMC, observed that "by itself an advisory committee hearing is not a very complete way of getting industry comments.

"The membership of FDA's advisory panels is usually not reflective of industry," added Thompson. "The members tend to be academics with little or no industry experience, and the panel meetings do not offer much opportunity for comment by industry, patients, or other stakeholders. In addition, the members are chosen by FDA, and subject to self-selective bias. In any case, holding advisory committee hearings would not fully address the concerns that are raised in the IMDMC petition."

Trautman agreed, noting that better channels for soliciting industry input might be found among such groups as the Harmonization Task Force and the International Organization for Standardization (ISO) Technical Committee 210, which is working on the application of quality systems standards to medical devices.

The burning question of how and when the revised GMP regulation should be implemented escaped from the September committee meeting without firm resolution. FDA presented several options for putting the full regulation into effect, with time frames ranging from 180 days to 18 months after promulgation. The agency also put forward an option that would have made the full regulation effective 180 days after promulgation, but with an unspecified phase-in period for design control issues. During that period, the agency would forego writing form FDA-483s for design control observations, but would issue "feedback reports" to help manufacturers learn what FDA expects in terms of design control.

The panel reviewed all of those options - and a lot of variations along the same lines - and we just could not agree," said Thibeault. "The most we got to support any one option was two people. So there was never any vote, no consensus, nothing. Now we don't know what will happen; FDA will have to make a decision based on what it thinks is best."

- Steven Halasey

(This article originally appeared in the November 1995 issue of Medical Device & Diagnostic Industry. © 1995 CanonCommunications, Inc. All rights reserved.)

Product Promotion Strategy Links Drugs and Devices

The trend toward disease management is forging alliances between device manufacturers and pharmaceutical houses that may ultimately benefit both the patient and the corporate bottom line. The strategy underlying these partnerships makes use of diagnostic products to increase demand for drug treatments.

Last summer, U.S. drug manufacturer Merck (West Point, PA) embarked on a program to support the broad distribution of x-ray bone densitometers made by Lunar Corp. (Madison, WI) and Hologic, Inc. (Waltham, MA), instruments used in the diagnosis of osteoporosis. Just weeks after those agreements were cut, Merck licensed bone densitometry technology from CompuMed (Manhattan Beach, CA). The drug company wants to make bone measurement tests as widely available as possible prior to the release of its osteoporosis drug, Fosamax, which has been recommended for approval by an FDA advisory committee.

Once the drug is commercialized, the more physicians who are capable of reliably diagnosing osteoporosis, the more prescriptions for Fosamax are likely to be written. While other therapies exist for osteoporosis, Merck's Fosamax will be the first nonhormonal drug to enter the market. The company wants to maximize sales upon its introduction, since competing nonhormonal therapies are expected to follow quickly.

The agreements with Lunar and Hologic call for Merck to pay a subsidy to the equipment companies for each bone densitometer placed with "high-risk" customers - small hospitals or group practices that have previously resisted buying or leasing these instruments because of uncertain patient demand. Merck's subsidies are intended to help offset that risk, allowing the two companies to provide more attractive terms to potential customers.

"We have agreed to place machines with qualified practices on a test basis, where the site is not committed to buying or leasing the machine over the long term," says Robert Beckman, Lunar's vice president of finance. At the end of one year, the sites would have the option to buy, lease, or enter into a fee-per-scan arrangement.

Unlike Hologic and Lunar, CompuMed does not make bone scanners. Instead, its product is a wedge of bonelike material. When placed in a standard x-ray, this material serves as a standard against which bones in the hand of the patient are compared to determine bone density. CompuMed's chief financial officer, De Vere Pollom, is excited about the deal because the device company "is not going to do the selling; Merck will do the selling." The wedges, he explains, will be distributed by drug retailers to physicians who might prescribe Fosamax if they could diagnose osteoporosis. Merck will pay a licensing fee and royalties to CompuMed for exclusive rights to use the technology for the next five years.

The deals pairing Merck with Hologic, Lunar, and CompuMed are the most recent, but not the only, agreements between drug companies and device manufacturers. Last winter, Astra Merck (Wayne, PA) cut an agreement with ChemTrak, Inc. (Sunnyvale, CA), to obtain exclusive U.S. marketing rights to ChemTrak's in vitro test for Helicobactor pylori, a bacterium that has been associated with duodenal and gastric ulcers. Although it has yet to receive approval from FDA, the finger-stick test promises a quick, easy way to diagnose the presence of H. pylori, which can be treated with Astra Merck's prescription drug Prilosec. Alene Holzman, ChemTrak's vice president in charge of sales, marketing, and business development, says that cutting such deals is part of the company's strategy: "As a company, we have had a philosophy of developing diagnostic products that marry well with therapeutics to provide overall disease management."

The availability of a simple diagnostic test might ultimately increase demand for ulcer drug therapy by putting the means for diagnosing H. pylori within the reach of not only every physician but virtually every patient. Astra Merck will not be the only vendor to benefit, but as the market leader, it has the most to gain from rising demand.

Whereas Merck plans to use established devices to generate demand for a drug that has yet to pass FDA review, the reverse is true for Astra Merck, which is banking on a technology that has not yet been submitted to FDA to increase demand for a drug it already has on the market. Making the AccuMeter test for H. pylori commonplace could grease the wheels for the market to adopt this novel device once it is approved.

In the case of drug company OncoRx (New Haven, CT) and device maker Response Biomedical Corp. (Vancouver, British Columbia), neither company has a product ready for sale. But that has not stopped OncoRx from entering into a sales and distribution agreement for a handheld diagnostic device from Response Biomedical that promises to offer a simple, cost-effective, point-of-care test for determining counts of white blood cells known as granulocytes. Oncologists would like to monitor these blood cell counts in cancer patients to ensure that the production of the granulocytes has recovered enough between doses of chemotherapy, which reduces the ability of bone marrow to make granulocytes.

At present, oncologists often forego the costly and time-consuming laboratory tests that are needed to determine these granulocyte counts and simply prescribe colony-stimulating factors (CSFs) to restore white blood cells - which has led some clinicians to suggest that CSFs are being overprescribed. A simple, disposable test could lead to more effective management of the rising costs of cancer treatment, according to William Radvak, president and CEO of Response Biomedical. "What we are trying to do is totally different from anybody else out there," he says.

The unusual approach, while distinguishing the company, also scared off some potential partners. "We couldn't get the big companies to team up with us," Radvak says. "They wanted to wait until the product proves itself in the market." OncoRx was not frightened away, however. The company agreed not only to usher the product through FDA clearance, but also to make milestone payments to Response Biomedical as the review process proceeds.

The two companies hope the diagnostic product will be ready for market in early 1997. OncoRx, which is focusing on products for the treatment of cancer, will have exclusive rights to sell and distribute the diagnostic device in North America. Because the firm completed an initial public offering in midsummer, corporate officers were unable to comment at press time on the strategy underlying the deal.

But the device technology does not have to be novel to benefit from the support of drug companies. In describing the benefits of the alliance Merck has formed with Hologic and Lunar, Joel Weinstein, HologicÕs vice president for marketing, says, "This program will make a big impact in reaching folks who otherwise would be reluctant to embrace a new modality and give it a fair chance to show what this technology is capable of doing for them."

More such deals can be expected from other companies in the medical device industry. In the past, diagnosis and therapy were two of the many different and often isolated components of health care. But the dawn of health-care reform and the growing popularity of managed care are forcing providers and vendors to recognize not only that these various components are related, but that they must be integrated.

- Greg Freiherr

(This article originally appeared in the November 1995 issue of Medical Device & Diagnostic Industry. © 1995 CanonCommunications, Inc. All rights reserved.)

An Interview with Susan Alpert

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

Originally published November 1995

Director, Office of Device Evaluation, CDRH, Rockville, MD

In the two years since her appointment as director of the Office of Device Evaluation (ODE) at FDA's Center for Devices and Radiological Health, Susan Alpert has become a well-known figure to the medical device industry. Ubiquitous at meetings and conferences and tireless in meeting with industry representatives, Alpert has displayed an openness that has met with widespread industry approval.

The primary challenges of her office in the past few years have been to bring down review times for product submissions and to eliminate the massive backlog of 510(k)s that threatened to bring industry to a grinding halt. While she admits that these tasks are not yet fully accomplished, progress over the past year has been dramatic, and industry seems now more concerned with the wide-ranging issues involved in FDA reform.

A number of these have also come to rest in Alpert's office - including industry proposals for third-party review of product applications, questions about the formulation and use of guidances, and complaints about the attitudes displayed by FDA reviewers toward industry. In this interview with MD&DI, Alpert discusses these and other issues that are now being considered at ODE.

FDA has recently released a revision of its guidance on 510(k) submissions for device modifications, which has been in the works since April 1994. What was the process for creating the revised guidance?

There was industry participation and sounding as we developed the first straw man, the draft that was released for comment in April 1994. During the announced comment period, and afterward, we received even more comments from industry, and these revealed concerns in certain areas, particularly in vitro diagnostics. Other issues included what to do about labeling changes, and how to integrate working with the matrix and flowchart that were the basis of the first draft.

Once these comments had come in, [ODE deputy director] Phil Phillips and [Office of Science and Technology acting deputy director] Harvey Rudolph gathered together a group of staff to sit down and pay really careful attention to the comments. This group also contacted members of industry and worked back and forth on some of the issues.

So when members of the group were considering a comment, they might call the person who'd made it?

Yes, in some cases, if they had a question about the comment. Or, if the comment came from a certain sector of industry, they might try to address it and then go back to representatives of that sector and ask, "Are we getting there?"

When the first draft of the device modifications guidance was released, the agency said that it was intended to be "submissions neutral" - that is, it would not stimulate a greater number of 510(k)submissions or result in fewer. Has that intent been carried over into the revised version?

Well, the intent is the same, but what the actual impact will be is really not clear at this time.

This guidance provides industry with information on the issues that need to be considered along the path to determining whether to file a 510(k) or merely to document the changes and handle them as good manufacturing practices (GMP) records. The guidance carries two strong messages. First, that record keeping is critical, and that manufacturers must record why a change was made and what its impact was. And second, that manufacturers need to maintain documentation to demonstrate the continued safety and effectiveness of their product after a change is made. For instance, if a labeling change expands the use of the product into new populations or provides new indications for use, the manufacturer needs to document the safety and effectiveness of the product under those new conditions.

With regard to manufacturing changes, we're not expecting manufacturers to file 510(k)s on every change order, and we don't want to see all of them. But again, it's a question of how many changes are being made and whether they have a significant impact on the safety and effectiveness of the device. Each company will need to evaluate its changes and determine when they cross the threshold for updating the 510(k).

One major difference between the April 1994 guidance and its new version is the latter's reliance on GMPs to keep track of the manufacturing changes.

Right. If all goes well with the July draft of the revised GMP regulation, all of this will become much easier for industry and for all of us. Because the design control requirements of the GMP regulation dovetail with the modifications guidance, the new regulation should go a long way toward ensuring that manufacturers collect and record the kinds of data that inspectors need to have on hand. By having reviewers rely more on the GMP documentation that companies have, the issue of manufacturing changes can be more often eliminated from consideration during the decision-making process about whether to file a 510(k) for a device modification. This is a simpler and easier way to handle the issue than the alternative of requiring 510(k) documentation.

How does the process used to develop this guidance differ from the one used for other guidances issued by FDA?

This process illustrates what we're trying to do in the area of guidance development. We're working out a more regularized process that is distinct from the formal notice-and-comment rule making used to produce big guidances.

I think we need to recognize that there really are different levels of guidances. At the low end, there are simple checklists that tell manufacturers the things they need to have in their 510(k) submissions. For the most part, these are compilations of information that has been developed over many, many years, and the checklists just put that information into a form that's easy to deal with. This type of information has already received an industry critique as part of the back-and-forth connected with the 510(k) review process, and compiling it into a checklist really requires minimal input from outside the review group; the division knows pretty well what the problem areas are. For guidances at this level, what we are attempting to do is compile the issue in-house. After all, guidances are a result of experience with a lot of submissions, or with a cluster of submissions.

What other levels of guidance would you distinguish, and how should they be compiled?

One level has to be devoted to new technologies - areas in which enough companies are developing products so that the agency needs to be giving them a consistent message. The goal of these guidances is to identify the issues that we know exist for the technology, and to spell out the areas FDA expects manufacturers to address in their submissions.

Guidances of this type are still one step back from the big guidances, and in making them we wouldn't expect to follow formal, 90-day, notice-and-comment rule making. Instead, we'd begin by brainstorming the issues in-house, then send the guidance out to industry for a short comment period. Probably, our notice to industry would indicate that the document is an active draft that is being revised, and that we intend to implement it in several months. So industry will be given a limited period to respond, and several months later everyone will be using the guidance.

And then there are the really high-impact documents, those like the device modifications guidance, that have potential for affecting industry on a broad scale. In those cases, we're trying to get industry and the clinical community involved early on, when we're just beginning to formulate the guidance. In this way, the agency's ideas can be sounded with industry as part of the preparation of a draft guidance. The draft can then be sent out for a formal critique, the comments can be discussed and incorporated, and a revised version can be sounded a final time. At this level of guidance there would be a lot more input from outside.

So the idea is to get industry input even for documents that the agency considers to be below the threshold for notice-and-comment rule making?

That's correct. If we were to try to do formal notice-and-comment rule making for everything we are trying to provide, the time frames for their appearance would become excessively long. Providing a framework for people to work in shouldn't take six months, or a year, or two years. Often, we need something right away, because if we wait, manufacturers don't know what they should be doing with their submissions in the interim.

ODE is really committed to getting out for comment any guidances it's developing on a new technology, or where it's making a major change in a guidance. One way we're doing this is by using our panel meetings; we're trying to make the documents available at the same time that panel meetings are announced in the Federal Register, so that anyone who is concerned can read the document and come to the panel meeting to comment on it. We're also making sure that appropriate trade associations and practice associations know that the documents are available, and we're making them accessible via the electronic docket and flash fax systems at the Division of Small Manufacturers Assistance.

In some cases, we're also doing workshops. One that was quite successful was on the reuse of dialysis membranes, where we issued a draft document and then worked back and forth with the affected industry to develop guidance for reuse labeling. At another workshop, sponsored by the North American Society for Pacing and Electrophysiology, the American Heart Association, and the American College of Cardiology, we looked at a draft guidance on clinical trials that they had created. In the course of discussing that document, the agency was able to talk about its regular target requirements and what sorts of things reviewers need to see in regulatory submissions. That interplay helped to make the draft more mature; it was later sent in for agency comment and panel review.

Do you encourage organizations to draft voluntary guidances that the agency can use as straw men for soliciting further input?

Absolutely. We've told industry and the trade groups that if they recognize an area where guidance is needed, they should feel free to put together a draft that can be sent in for agency comment. The agency can then add in the necessary regulatory bells and whistles, and send it back for further comment or adoption.

We're doing the same thing with the clinical community. In the area of orthopedics, we recently participated in a meeting sponsored by the American Orthopaedic Association, the American College of Orthopedic Surgery, and the Orthopedic Surgical Manufacturers Association, to discuss how to oversee and control new technologies, and how to develop them correctly. The meeting included representatives invited from manufacturers, the clinical community, the academic community, the research community, and the regulatory community - the National Institutes of Health, the National Institute of Standards and Technology, and FDA. It resulted in identifying some key areas - particularly for orthopedic implants - where there is a need for guidances and for a consensus on what data are needed to support submissions and how to go about getting those data. Now the sponsors have an agenda for drafting additional guidances and points-to-consider documents, and for creating a reasoned approach to the development of new technologies and biomaterials testing. These issues are really important, and they affect all of us. There shouldn't be a unilateral decision on anybody's part.

How does this approach to guidances respond to the criticisms put forward in the citizen petition submitted by the Indiana Medical Device Manufacturers Council?

Essentially, the IMDMC petition asks that FDA refrain from all informal rule making. In effect, the group is proposing that all of these types of documents be developed with notice-and-comment rule making.

Congressman David McIntosh [R-IN] has announced that his panel on National Economic Growth, Natural Resources and Regulatory Affairs will be holding hearings on the IMDMC petition in September, and it will be interesting to hear the views presented there.

Is the guidance development the same as rule making?

We don't believe it is. We believe guidances and points-to-consider documents fill different needs of the community. But the petition's point is that when FDA generates these documents, essentially they are handled as though they were rules and regulations. That's the issue the group is trying to address.

Another issue that the petition points out is an important one, namely, that guidances are not intended to be rules. Guidances are signals from FDA to industry indicating the easiest path to market. It's all right if manufacturers choose to take another path - they know best how to develop their products - but doing so may impose additional requirements on them to validate and explain to the agency what they've done.

Guidances embody the issues that FDA has learned are important in a particular device area. So if a manufacturer has a different view of what the real questions are, or a different set of tests to answer the agency's questions, those will need to be explained to the reviewers. It's a bit more work, but it's perfectly acceptable.

We have made it very clear to staff that guidances are not regulations or requirements. We cannot set thresholds or absolute criteria for anything in a guidance document.

How does the agency train staff not to enforce guidances or points-to-consider documents as though they were regulations?

We at CDRH are working closely with frontline staff to help clarify the true intent and proper use of guidances, and the impact they should have. We have a lot of new staff, and guidances are the sort of tools that a reviewer can ignore, use, overuse, or abuse - and only one choice is correct. Luckily, overuse and abuse have not been pervasive at ODE. But we have been made aware of some situations in which staff members told companies that if they didn't follow the guidance, the office would not review their submissions. That's not appropriate, and we've let staff know it.

Another issue that we watch very closely is the protection of proprietary information - making sure that reviewers do not use the information in one submission to fill in the blanks of another. In the scientific community, everyone reads everyone else's papers, and the thoughts are combined to move the field forward. But reviewers are precluded from doing that. So we have to teach our staff to deal with each submission on its face. They can't take data from one and have them support another; each submission has to have its own data.

To train staff, we're conducting essentially three levels of training. First, there's general training in the process. No one comes to FDA understanding the FD&C Act, IDEs, PMAs, 510(k)s, GMPs, GLPs, and all the alphabet soup of any regulatory agency. So we have basic training.

Second, we have division-level training in each of the divisions covering certain approaches and specific issues that the division faces. Clinical laboratory devices, implants, orthopedics, and ophthalmics are each very different, so each division has its own internal training.

Third, new employees participate in a mentoring program, where they are assigned one or two senior individuals in the division with whom they have a student-teacher relationship. Review work is not taught anywhere, so new employees need guidance from someone who has been through the process. The mentors can show new employees what a good review is, and what pitfalls to avoid. They can also teach new employees what their role is vis-à-vis industry, how to communicate with sponsors, and how to document.

In addition, the CDRH Staff College in the Office of Health and Industry Programs, which is overseen by Jerry Jenson and Marvin Rosenstein, is developing core training programs. The courses in the college are for both new and seasoned reviewers. The college recently offered a course on clinical trials taught by many staff members, including [CDRH director Bruce] Burlington, me, and staff of the Office of Biostatistics and Surveillance. It covered FDA's role in the oversight and development of clinical trials, what device trials are intended to do, and the models that exist for conducting a device trial.

We also have other training programs, and they are not restricted to ODE staff. We are trying to provide an educational environment for staff - to train them to understand the GMP and medical device reporting regulations, for instance. Mostly, this training is teaching by example, by way of the senior managers who set the goals and performance characteristics for their units. And I can't think of a better way for new employees to learn.

When does a new technology reach the point at which it is possible to write a guidance, and how do you get staff up to speed on new technologies?

Two years ago I would have said that we needed to have some in-house experience with a few submissions before we could write a guidance, but that's no longer true. Industry has been tremendously willing to come in early - at the pre-IDE stage or even earlier - and to help teach our reviewers about emerging technologies. This simplifies matters considerably, because the presenters are not talking about a particular product submission, and the reviewers can instead focus on learning about the science. Then our staff can figure out where they need more training, locate appropriate courses, read up on the subject, share information, and get some self-training. And once the IDE is up and running, staff can continue to stay on top of the changing technology.

These are the kinds of areas where industry can take a lead in helping us develop guidances. It can help us identify the areas where there will be a need for guidance, explain the latest trends, and share with us the latest publications and minutes of international meetings. Industry can initiate the process by suggesting a meeting where some early decisions about the review requirements can be made.

We've seen the industry be very willing to take these steps, and we welcome that involvement.

How is the medical device industry involved with ODE now?

Industry is playing a key role in helping us bring review staff up to speed on what they do. It's very important that the review staff understand the industry, the actual technology they're dealing with, and the devices they encounter. And hands-on experience is the best teacher.

We're conducting three types of training programs that involve industry. The first is to send reviewers on industry site visits. We don't have a lot of funding for that, but we have been able to use some of our operating budget to send groups to see manufacturing sites. Many of our staff members are new to either industry or FDA. They are well-educated academicians who may not have seen the actual implementation and use of certain technologies, and may never have seen a manufacturing plant. So educational plant visits are really valuable.

A second program involves sending members of the product review team on real preapproval plant inspections. They understand the technology, and they can help the field and compliance staff understand what they are seeing. They can also make the inspection more productive and reasonable for industry.

The third activity is a vendor day program, where manufacturers bring their products into CDRH, set up displays, and talk about the basic technologies involved in their devices. This is literally hands-on experience for our staff, and it goes a long way toward improving their understanding of device technologies. We had a vendor day on defibrillators and pacers, and another on genetic amplification technologies for the clinical lab group, and we're looking forward to more. We really owe a lot of thanks to the companies that have been willing to participate; without their cooperation it couldn't happen.

Many in the device industry are now recommending that FDA adopt the European model of using third-party reviewers for both product approvals and compliance activities. How might the agency go about ensuring that those reviewers are qualified?

Well, that is going to be a challenge, and it's one of the questions we're wrestling with. We expect that one piece of the model will involve a system for accrediting those bodies, and that would include demonstrating that their staff have adequate engineering and scientific backgrounds for performing the kind of evaluation that is expected.

We will clearly have to provide some training and guidance, and we are gearing up to do that. We will need to provide the third parties with our own guidance documents, and we will clearly have to be accessible to answer questions - particularly at the beginning. Beyond that, our job would be to perform a secondary review - to make sure that the third parties have looked at the aspects that the agency considers important in comparing a device to its predicate, to review their documentation, and to determine that we agree with their recommendation.

These issues have a lot to do with how we selected the types of devices that are included in the pilot program for third-party review. The products we chose really do need oversight; someone needs to see that they actually match their performance characteristics, and that they are substantially equivalent to what is currently on the market. We intentionally selected devices with which we have sufficient experience, and for which good and complete guidances exist. We also looked for devices that could include consensus standards as part of the review, or for which the testing methods are well accepted by the manufacturing community.

Is the primary goal of the third-party pilot program to get products reviewed or to test the viability of such a program?

The pilot program will get products reviewed, but the main idea is to determine whether or not outside groups can do a 510(k) review. We're starting with simple products, and we're hoping that this is the right threshold. We know that it would be a bit much to expect a testing company to come up with a very large and sophisticated organization just for a pilot program. So we are trying to do things in a very straightforward manner, with a lot of guidance, so that existing groups can fill in the pieces they don't have and do the review.

My personal expectation is that there are groups that can perform a straightforward 510(k) review. We have been told by some outside groups that they already do a lot of similar work for both government and industry, and that they are qualified to do it.

So the shape that's been given to the pilot program may not be the eventual shape that a third-party review system would take on. When will the agency begin to evaluate the results of the program?

I think we have to have an ongoing measure of how the program is working, and that has been designed into the program. We need to be able to make midcourse corrections, to consider how the program could be developed and expanded beyond the pilot stage, and to begin preparing for that next stage. I don't know any other way to go into this type of program.

So, assuming that everything succeeds, the pilot program would grow incrementally into a full-blown program?

Assuming that things work well and that we get positive results from the program, I don't see why not. But right now, what we're committed to is a two-year trial. We are developing the model, and we are going to see how it flies and evaluate it while it's flying. The whole reason for conducting any kind of pilot program is because you are not really sure whether it's going to fly or crash.

Given that third-party-review systems are in use in Europe and elsewhere, would FDA adoption of such a model improve the accessibility of foreign markets to U.S. manufacturers?

Well, I don't know whether access to foreign markets necessitates a third-party system. That question is probably better addressed by the development of consensus standards that cover an increasing number of device development and evaluation procedures. Eventually, there would be enough standards in place that simple assessment of compliance with them would constitute the review, with only labeling and regional differences needing to be evaluated separately.

What we see as the advantage of the third-party model is that it enables the agency to face this period of shrinking resources, when there are fewer people and financial resources to perform a large volume of work. We need to continue a program that ensures that all of the products on the market are safe and effective, and one way to do so is to have more than just FDA participating in the evaluation of products.

New technologies can significantly affect the nature of health care, but they require a lot of upfront attention if they are to be given a streamlined route to market. FDA would still be seeing the newest of the new, but there are other groups that can facilitate getting and maintaining other products in the marketplace.

We don't think old products ought to suffer for new, or that new products ought to suffer for old. They all ought to get attention, and that's going to require some managing on our part.

Are you concerned that implementation of a third-party system for product approvals would put your office out of business?

I'm not at all worried. However, that is a very-often-discussed concern at certain levels within the staff.

If you look at other jurisdictions around the world, you can imagine why. In the United Kingdom, only medical device reporting and related areas remain as government functions; otherwise, the system is almost totally privatized. For device evaluation, the UK system is funded totally outside the government. In some of the other European countries, it's all notified bodies with minimal government involvement.

But our process, issues, population, and health-care needs are quite different from some of those other jurisdictions. Not better, not worse - just different. The U.S. system has developed differently and has different approaches to what is expected in the delivery of any technology for health care.

I am not worried that we are building our own demise. I think there is plenty of work. The challenges of brand-new technologies, of developing guidances and evaluation procedures for them, and of getting them to market convince me that we are not putting ourselves out of business.

Do you think that the focus of your office might shift toward reviewing the reviewers?

There is concern that we would be regulating at a distance - regulating the people who are actually regulating. Anything is possible, and I think that there may be some of that in our future. We will be smaller in the future, and I think we will be focusing our attention differently on how we regulate technology and new clinical advances. And while my crystal ball doesn't work well enough to really say for sure, we will probably be doing some of our work through other parties.

(This article originally appeared in the November, 1995, issue of Medical Device & Diagnostic Industry. © 1995 CanonCommunications, Inc. All rights reserved.)