CLIA Waiver for IVD Medical Devices

"The plan is useless, but planning is essential." --Dwight D. Eisenhower. "I need to see your useless plans in order to know you have been planning." --Zi-Ping Fang, Manager.

Project management falls into five broad phases, whether the project is to conduct a clinical trial, throw a birthday party, or go to the moon:

1. Concept
2. Planning
3. Implementation
4. Maintenance
5. Close-out

But embedded within those phases are a myriad of details, starting with Gantt charts and budgets through cost-analysis, metric tracking, site and study maintenance, and close-out issues.  

Most device companies, small or large, don't apply their project management skills to clinical trials; then they are surprised that six months passes before before the first subject is enrolled, or when as much as 60% of the study budget is spent before the first subject is enrolled, or or that subject recruitment is the rate-limiting step.

I wrote this book at the request of a smart client who recognized that traditional project management skills could be applied to planning a clinical trial, and it would give top management better information for making decisions.

After it's first debut it was clear that clinical research managers needed more than just simple project management, they needed schooling in contract law, managing CROs, and common communication problems. The second edition addresses all these issues.

Medical Device Biological Safety
The biocompatibility of medical devices is approached differently in the States than it is in Europe. FDA prefers a data-based approach. Europe prefers a literature-based defense. In either case, following the ISO 10993 or ISO 10993/G95 matrixes is only a beginning; the data supporting the biological safety of the final device must give 'reasonable assurance' of its safety in real use situations. You need to play 'devil's advocate'; thinking of all the ways your device might cause a biological reaction with the body and then address each possibility with data, proposed labeling, and a plan for mitigation.

For example, FDA raised the question if an implanted material might have a local oxidative effect. The question required the design of a unique animal test and a focused literature search reviewing the chemistry of the materials. In another example, FDA wanted to know the concentration of unreacted monomers, bimers, and trimers to the ppb level in a plastic, the analytical testing required a unique design. In a third example, reviewers wanted to know the possibility of an implanted material injuring a nerve, the solution required a sub-chronic test in which devices were implanted in dogs.

Clinical Device Group's Rescue Squad
Your first contact with Clinical Device Group will be with Nancy J Stark, PhD. With a doctorate in biochemistry, Dr. Stark will assess your biological safety questions and determine if the firm is able to help you. She will answer your initial questions about the company, its history, services, and rates; will sign a confidentiality agreement and negotiate a service agreement with you. Once the administrative end of the relationship is in place, you'll be referred to our primary toxicologist, Dr. Daniel McLain.

The Expert Himself
Next you'll be referred to Dr. Daniel McLain, MS/PhD, Nutritional Toxicology and Preventive Medicine, who will begin immediately to assess your issues and recommend strategies and solutions. He may recommend a literature review, he may provide expert interpretations of laboratory reports, he may recommend additional testing at the test house of your choosing, he may assist in writing unique protocols for sub-chronic or chronic tests, or he may provide expert justifications of safety based on the data you have now. Dan can prepare risk assessments, preclinical strategies, or prepare the biological safety sections of 510(k)s, PMAs, or BLAs.

Dr. McLain is an internationally recognized toxicologist in the medical device industry and currently serves as the Convener for ISO 10993: Biological evaluation of medical devices – Part 11: Systemic toxicity evaluation. It is an extreme honor to serve as a convener, because it is a nomination of your peers, recognizing your expertise in the technical area and ability to work with people to bring them to consensus. He has had extensive interaction with global regulatory bodies as it pertains to product safety submissions and is held in high regard for his development strategies and commitment to product safety.

Now for Some Fun
First, click on the image to the right to solve the puzzle of biological safety.  

Second, take Poll du jour 6, a 30-second quiz about FDA's views on biological safety and see how your answers compare to others.

Contact Us
Clinical Device Group Inc
773-489-5721
mailto: cdginc@clinicaldevice.com

We don't usually associate 'choice' with regulatory submissions. Usually we think of the requirement for a 510k or PMA as being cut and dried--the decision is already made, our job is to figure out what the decision is.

In this e Conference I've invited Janice Hogan (of Hogan an Hartson) to teach us how we, as manufacturers of medical devices, do have choices about our regulatory strategy. The type of submission we need depends on the claims we want to make for the device. The claims we want to make may be influenced by market forces as well as the device's physical performance.

For example, if I have a department full of people who know how to file a PMA, I'll be sure to word my claims so that a PMA is required and I can roadblock for my competitors. But if I'm a start-up firm and getting venture capital is my worry, I'll go after the easy claims first. My primary goal being to demonstrate that I can get a submission through FDA and generate income.

Work with the words...that is part of the message Janice will bring. If you are a regulatory professional in medical devices you should plan to attend this lively and informative e Conference.

When FDAMA first came out in 1997, Congress instructed FDA to find a way for device manufacturers to make changes during the course of a clinical study without having to get prior approval. Eventually, §812.35 IDE Supplements was issued. It is a short section, just a couple of paragraphs. The real meat is in a guidance document called Changes or Modifications During the Conduct of a Clinical Investigation (May 01).

In the guidance FDA identifies three categories of IDE amendments: administrative changes (to be tabulated in the annual report), non-significant amendments (the sponsor can make the change and tell FDA later in a 5-Day Notice), and amendments (changes which require prior FDA approval.)

If we think about it, non-significant amendments are really planned deviations, and we can use this guidance to develop policies for managing the many clinical trial deviations that inevitably occur.

In developing the 3-hour workshop "Deviations and Amendments" I used this logic to walk through many examples of deviations taken from FDA warning letters with the goal of being able to identify deviations when they occur in a study and determine the reporting requirements. If you are a monitor who is responsible to identify deviations in the field, or a manager responsible for reporting them, this workshop will help clarify your thinking. --> more information

Medical device companies are shifting their allegiance from Republican to Democratic. In this election cycle, Democratic candidates have received $7.4 million in campaign contributions from political action committees and individuals associated with medical device and pharmaceutical companies according to the Center for Responsive Politics. In the past six election cycles, device and pharma companies contributed twice as much to the Republican candidates as to the Democratic candidates.

Why the shift from Republican to Democratic? Does the industry itself perceive change in the air? Overwhelmingly, Americans want some kind of universal health care in this country. I'm in favor of it too, but most Americans think Europeans have a dreamland situation—free health care for everyone, anytime. But it isn't so. In the UK, public health care is often augmented by private health insurance. And universal health care can lead to political tensions. In Denmark, 60-70% of salary goes to taxes, including taxes to finance the 'free' health insurance. Yet those who don't work and don't contribute to the system still have access to it, meaning a large minority of immigrants from Middle Eastern countries are taking advantage of the system.

If the Democrats are more likely to actually implement a universal health care system, then it makes sense that device and pharma companies would want to be in a position to influence how that system is constructed. Will there be a single-payer system, doing away with the 350+ health insurance companies in this country (I hope so)? Who will have access to it: all persons or only citizens? Will the entire reimbursement scheme be rebuilt? Today, devices are not usually reimburse as separate entities, but rather as part of a procedure. So an incremental improvement to your medical device doesn't automatically get you a better price, because the differential comes out of the hospital's pocket. How would the reimbursement system change and would it benefit the device industry?

CDG recently sponsored a conference on medical device reimbursement and it is now available on CD or On Demand video. You can learn more about our reimbursement practices today, and interpret for yourself the complexities of implementing a universal health care system, by viewing Mary Ann Clark, VP for Health Economics & Reimbursement for the Burgess Group, at CDG e Conferences, or call me          773-489-5721       .

FDA has banned seven doctors from doing clinical trials so far this year. That is the highest number since 2002, you can see the entire disqualification list at  http://www.fda.gov/ora/compliance_ref/bimo/disqlist.htm. Physicians or other medical professionals are banned from conducting clinical trials that will result in data being submitted to FDA; put another way, these people can still do clinical research, but no data generated by them can be used to support an FDA marketing application. Which means that medical device companies who have ongoing clinical trials with these investigators, or are considering using these investigators, should look elsewhere.

The list of investigators banned in 2008 is:

01/31/2008 Jamie Kapner, M.D.—Urologist, Scottsdale, AZ
02/15/2008 Bertrand Agus, M.D.—Rheumatologist at New York University
02/25/2008 Stephen D. Rossner, M.D.—Cardiology Associates of Central Connecticut
03/05/2008 William H. Ziering, M.D.—Pediatric Allergist, Central California Research Institute
03/05/2008 Mary Sawaya—Dermatologist, University of Florida, Miami, FL
03/21/2008 Patrick J. Daley—Pediatrician, Tulsa, OK
04/28/2008 Manjeet Kaur Achreja, M.D.—Family Medicine, Seagrove, NC
05/06/2008 David N. Lofgren, M.D.—Pediatrics, Sandy, UT
05/15/2008 James C. Vestal, M.D.—Urologist, Urology Associates of North Texas
06/02/2008 Maria Anne Kirkman Campbell, M.D.—Weight Loss Clinic, AL

The physicians come from various walks of medicine, but all contributed to fraudulent data being submitted to FDA. Fraudulent data is the omission of data, the fabrication of data, or the alteration of data. It can be committed by anyone who has contact with the data, but is usually committed by someone likely to experience financial gain. Investigative sites should be audited by third-party CROs whenever data are pivotal to proving your device's success. For information about site audits contact CDG. 

I didn't understand until recently why in vitro diagnostic device companies had to worry about CLIA waiver. CLIA, the Clinical Laboratory Improvement Act, is a certification for clinical laboratories. An individual laboratory is certified according to the complexity of in vitro diagnostic test they are qualified to run. The idea is that laboratories who have the best trained technicians, experienced PhDs as laboratory directors, and the most modern equipment are the laboratories that perform the most complex of diagnostic tests; laboratories with lesser trained technicians and less equipment perform the simplist of IVD tests. But I always considered it to be a laboratory issue, not a medical device manufacturer's issue.

Then comes the new FDA guidance "Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices" 30 Jan 08, http://www.fda.gov/cdrh/oivd/guidance/1171.html#1, and suddenly a light-bulb comes on. Of course a manufacturer of IVD devices wants their product to be 'waived' because it means they can offer the device for sale to more laboratories. The marketplace increases as the level of complexity category decreases.

I got so excited I asked Dr. Gail Radcliffe to give a virtual e conference on the topic on 11 June. Learn more....

In a Press release issued 22 May 08, HHS Secretary Mike Leavitt announced new efforts to help FDA improve the safety and quality of medical products. By 2014 FDA will proactively access Medicare Part D (drug reimbursement) information and private-payer information to determine what, if any, adverse events have occurred. The report is available at: http://www.fda.gov/oc/initiatives/advance/reports/report0508.html.

I have more reactions to this as a consumer than as a professional. I know first hand that delayed-type hypersensitivity reactions are underreported. My own allergic reactions were reported and were, frankly, boring to my doctors once they determined that I would live. Furthermore, it wasn't clear what caused the problem, I was exposed to half-a-dozen medical devices during a procedure, any of which could have been the sensitizer. Since there was no way to know, no one knew what to report, including me.

Accessing masses of data and looking for patterns may be the best way to identify what's causing what--both for drugs and devices. It's a little 1990-ish to have the FDA looking at my private medical information, yet a practical necessity for the safety of all. 

The CMS final rule and a related fact sheet may be viewed at www.cms.hhs.gov/PrescriptionDrugCovGenIn/08_PartDData.asp