CDG Whitepapers

Reimbursement Strategies for New Technologies

A Whitepaper by Dr. Nancy J Stark and Dr. Vincent Jaeger

Reimbursement strategies
A reimbursement strategy is a plan for: 1) working in clinical research to design studies that show "medical benefit" and "added value" to secure coverage; 2) identifying codes for new technologies (i.e., drugs, medical devices, medical and surgical procedures and services); 3) working with the FDA to phrase the intended use and indications for use to fit coverage and coding; and 4) presenting the clinical trial data to the Centers for Medicare and Medicaid Services (CMS) for reimbursement approval. Ideally, reimbursement strategies must be part of the early-on process of development for every new technology. Unfortunately, most manufacturers wait until they launch their product or are faced with resistance from Medicare before they begin to formulate a pathway toward reimbursement.

Reimbursement is the primary driver to profitability of a new technology in that it assures the all-important revenue stream that keeps a company viable. Medicare, by far the largest third-party payer, is limited by the Social Security Act to only cover technologies that are "reasonable and necessary" for diagnosis or treatment of diseases, conditions or injuries. (1 Social Security Act) In this whitepaper, Dr. Vincent Jaeger and I will review only the Medicare reimbursement process with the understanding that, because of its size and influence, private payers will usually adopt the same or similar coverage, coding and payment policies.

The challenge of new 510(k)'d technologies
Isn't it interesting that one of FDA's missions is to foster medical device innovation, (2 FDA & Innovation) but CMS has no parallel mission to reimburse it? Approximately 5000 510(k)s are cleared by the FDA each year, and most of these represent incremental improvements to medical devices and other technologies already on the market. Medicare’s bundled payment systems, i.e., diagnosis-related groups (DRGs) for inpatient care and ambulatory payment categories (APCs) for outpatient services, allow payment for incremental improvements without additional clinical evidence. Most 'new' technologies fall into the bundled payment system and do not face a full reimbursement challenge.

 

Although it is often possible to make a substantially equivalent argument to the FDA and gain 510(k) clearance to market a new technology, the technology may not meet Medicare's bundled-payment requirements or qualify for reimbursement. Some start-up manufacturers don't realize that it can take 3-4 times as long or more to gain CMS coverage as it took to get 510(k) clearance and that approaching the necessary activities to gain reimbursement in a sequential manner will unquestionably add to the overall timeline. The most serious obstacle facing manufacturers is not gaining FDA approval, but securing a positive reimbursement decision by Medicare.

Reimbursement decision process
The term reimbursement is used to describe activities related to the mechanisms by which patients have access to medical technologies through their health insurance payer. The elements necessary for reimbursement are: [1] coverage; [2] coding; and [3] payment. (3 Innovators' Guide) It is most important that a strategic plan is begun early in product development to ensure a positive coverage and reimbursement outcome. It is imperative to develop parallel regulatory, clinical and reimbursement paths that address the needs of both the FDA and the payers who ultimately control the technology’s marketing destiny through their policy-making decisions. Hospitals and physicians may use the device, but public and private payers reimburse and they set the rules.

 

Coverage
Coverage refers to the terms and conditions under which Medicare and private payers will (or will not) provide payment for drugs, services, procedures and medical devices. Coverage is the first, and unquestionably the most important, component of the reimbursement process. The decision for or against coverage of a new technology is directly related to the presence of valid scientific evidence from well-designed comparative clinical trials published in the peer-reviewed medical literature. The evidence must support the medical device’s effectiveness in substantially improving health outcomes over existing technologies. Over the last twenty years a system for ranking the quality of evidence has been developed and is known as evidence-based medicine. (4 Jaeger) Randomized, blinded, controlled clinical trials designed to overcome the many possible sources of bias rank as the highest quality of evidence. Testimonials rank as the lowest quality of evidence. (5 Evidence)

In May 2000 Medicare published a Notice of Intent (NOI) proposing a set of criteria to be used for determining which items and services are reasonable and necessary and therefore eligible for coverage. (6 NOI) The NOI proposed that technologies must demonstrate "medical benefit" as well as "added value." But just how medical benefit and added value should be measured remains controversial.

.....Registry studies
Randomized controlled trials (RTCs) for new technologies are sometimes difficult to conduct because physicians, surgeons, interventionists and patients are often reluctant to compare the new technology to an existing standard of care. And blinding device studies is usually an impossibility.

In these circumstances, registry studies, conducted according to the Agency for Healthcare Quality and Research (AHRQ) "Registries for Evaluating Patient Outcomes: A User's Guide", lend themselves well to comparative studies for commercial medical technologies. (7 Registry User's Guide) (8 Stark) Registry studies have been successfully used by manufacturers to gain CMS coverage. (9 CMRI) A registry study is research carried out in a prospective, observational manner in which subjects with certain shared characteristics are studied, and ongoing and supporting data over time is collected on well-defined outcomes of interest for analysis and reporting. Investigators are instructed to select and use 510(k) cleared devices as they would in their normal practice. The protocol refrains from dictating treatment or follow-up care. The value is that objective, observational data comparing new technologies to other technologies already being used can be gathered. These effectiveness data address benefits, outcomes, complication rates, adverse events, and deficiencies in real practice settings.

Don't be misled, a well-controlled registry study costs about the same as a well-controlled clinical trial. It requires a protocol, case report forms, informed consent, IRB review, monitoring, data collection, data analysis and a final report. The regulatory advantage is that the study is exempt from the Code of Federal Regulations (CFR), Title 21, Part 812 - Investigational Device Exemptions.

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Codes, codes, codes
There is no lack of codes. There are current procedural terminology (CPT) codes used primarily to identify medical and surgical procedures and services performed by physicians and other health care professionals. ICD-9 (International Classification of Diseases, 9th Revision) codes, used in both the inpatient and outpatient settings, convey a patient’s diagnosis(es), and provide the medical justification for the episode of care for which the provider is filing a claim. There are ICD-9 procedure codes primarily used by hospitals to identify and define procedures performed during an inpatient stay. Codes for diagnosis related groups (DRGs) are a classification system developed by Medicare as part of the prospective payment system for inpatient care. There are T-codes for emerging technologies, as well as nondescript codes (-99 codes) to identify new medical technologies until a specific code is assigned. Healthcare Common Procedure Coding System (HCPCS) codes are intended to report supplies, medical equipment and services that are regularly billed by suppliers, not physicians. (10-Clark) ICD-10 will add a new complexity to the mix in 2013.

In other words, code sets have been created to accurately describe and convey information between the various providers of healthcare and payers about medical diagnoses, procedures, products and services rendered to patients. These codes, when placed on a claim form, operationally link coverage to payment. When seeking reimbursement, it is better for the manufacturer to have an existing CPT code that adequately describes the procedure which is recognized by payers as valid for payment levels acceptable to physicians.

  

No Codes?
If there is no existing code which adequately describes the new medical technology, application for creation of a new code must be made to the appropriate committees within CMS and the American Medical Association (AMA): ICD-9 diagnosis codes to CMS, CPT procedural codes to the AMA, and HCPCS codes to CMS. New code applications are received on strict deadlines and take a long time for approval, which certainly is a major factor in the long delay for reimbursement approval by Medicare.

....Step 1—CPT
The first step in obtaining codes is to apply to the American Medical Association (AMA) for a CPT code. The AMA first developed and published CPT in 1966. The first edition helped encourage the use of standard terms and descriptors to document procedures in the medical record, helped communicate accurate information on procedures and services to agencies concerned with insurance claims, provided the basis for a computer oriented system to evaluate operative procedures, and contributed basic information for actuarial and statistical purposes. (11 AMA & CPT codes)

 

To ensure that physician services across all specialties are well-represented, the AMA established the Relative Value Scale Update Committee (RUC). Annually, the RUC makes recommendations regarding new and revised physician services which are then accepted, rejected or modified by CMS. As such, the RUC significantly influences the relative value units (RVUs) of CPT codes and, as a result, how much physicians are paid. The impact of the RUC becomes even more important when one considers that Medicaid and private payers tie their fee schedules to Medicare's.

The first step in obtaining a new CPT code is to make application to the AMA, specifically, to the Department of CPT Editorial Research and Development. The AMA staff reviews all applications to evaluate their coding suggestions. If they determine that the request is a new issue, or significantly new information is received on an item that the CPT Editorial Panel reviewed previously, the request is referred to appropriate members of the CPT Advisory Committee. If the advisors concur that a new CPT code should be added or a change should be made to an existing CPT code, the application is approved. If two or more advisors disagree, the issue is referred back to the CPT Editorial Panel for resolution. The Panel meets three times each year, evaluates approximately 350 new technologies and deletes those procedures that are outmoded.

....Step 2—ICD-9-CM
The second step is to apply to the Coordination & Maintenance Committee at CMS for an ICD-9 code. (12 ICD-9) This Committee provides a public forum where thoughts and comments are given; however, no decisions are made. All final decisions are made by the Director of the CDC’s National Center for Health Statistics (NCHS) and the CMS Administrator. Tentative agendas for the scheduled meetings are usually posted one month in advance.

Applicants can make presentations at these meetings, describing the clinical issues of their products. The participants at the meeting are encouraged to ask questions concerning the clinical and coding issues and to offer recommendations to those applicants requesting a change. Recommendations concerning proposed code revisions can be made either at the meeting or in writing before the end of the comment period. Final decisions on code revisions are made through a clearance process within the Department of Health and Human Services.

....Step 3—HCPCS
HCPCS is a standardized coding system that is used primarily to identify services (such as ambulance services) and durable medical equipment (DME), prosthetics, orthotics, and supplies (DMEPOS). These codes are primarily used by medical suppliers, so they are typically not costs that get passed through a physician's office. HCPCS coding is intended to be used to identify DMEPOS and formulate fee schedules in a consistent manner for billing purposes. "Level III" HCPCS codes refer to Medicaid and other state and local codes.

The preliminary step in the process for recommending a modification to the HCPCS coding system for DMEPOS is to contact the Statistical Analysis Durable Medical Equipment Regional Contractor (SADMERC). (13 Level II) CMS contracts with SADMERC to provide assistance to the public in determining whether or not a HCPCS code exists which describes the new product. If none is found, an application form for a new code, a cover letter outlining the new code request and a brief summary of why the code is needed should be submitted to CMS, together with the FDA letter confirming 510(k) approval, data supporting clinical effectiveness, and product brochures and/or booklets. Samples of the device can be included with the application. Once the application is received, the product is placed on an agenda and reviewed by a panel whose membership includes representatives of Medicare, Medicaid, and private insurers. These informal, public meetings permit interested parties to make oral presentations or to comment in writing regarding the coding issues.

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Vincent Jaeger, MD, a proven expert in reimbursement strategy, has 15 years experience in evaluating new medical technologies for Aetna, Health Net, and Connecticut Health Network. Dr. Jaeger’s considerable experience on the payer side now qualifies him to offer his advanced skills and knowledge to the medical technology industry to ensure a positive coverage and reimbursement outcome. No matter where you are in the developmental cycle of your new technology, Dr. Jaeger can help you create a reimbursement strategy which will ensure commercial success of your product and generation of the all-important revenues you need to keep your company viable. Phone or email us at 773-489-5721 or cdginc@clinicaldevice.com.

Council on Technology and Innovation
The Council on Technology and Innovation (CTI) at the Centers for Medicare & Medicaid Services (CMS) oversees the agency's cross-cutting priority on coordinating coverage, coding and payment processes to enable CMS to more efficiently identify high value technologies and services that will improve healthcare quality and the lives of Medicare beneficiaries. (14 CTI) CTI is developing the capacity to better prepare for new kinds of medical innovations. The agency recently issued a revised guidance on Coverage with Evidence Development (CED). (15 CED)

Payment
Payment refers to the amount of monetary compensation provided to the physician and other healthcare professionals who use the new technology. It is important to realize that Medicare pays for the procedure associated with a medical device, not for the device itself. Medicare’s inpatient and outpatient prospective payment systems include provisions designed to provide an extra payment amount for certain new technologies. To merit such additional payment, the new technology generally must represent a substantial clinical improvement relative to existing technologies and meet specific cost thresholds. (16 Innovator's Guide)

Conclusion
FDA approval, clinical trial outcomes data, the presence of appropriate coding and payment levels are vital for reimbursement of new technologies. The quantity and quality of the outcomes data arrived at by randomized controlled trials (RCT) or an observational, well-controlled registry study will dictate the decision for or against reimbursement. Products with explicit reimbursement pathways to increase revenue are more likely to be used by providers than products with limited or no coverage. As improper coding is often the cause of Medicare’s delayed or denied payments to providers, manufacturers must make certain that an identifying code is clearly available for placement on the insurance claim form. The somewhat long and drawn out timeframe for coverage can be reduced if a thoughtful reimbursement strategy is implemented at the earliest stages in product development.

References
(1 Social Security Act) Title XVIII, The Social Security Act of 1965, sec. 1862(a)(1)(A).
(2 FDA & Innovation) http://www.fda.gov/downloads/MedicalDevices/NewsEvents/WorkshopsConferences/UCM192268.pdf.
(3 Innovators' Guide) https://www.cms.gov/CouncilonTechInnov/Downloads/InnovatorsGuide5_10_10.pdf.
(4 Jaeger) Cost Effective Analysis and Medical Device Utilization (Nov 2009).
(5 Evidence) http://en.wikipedia.org/wiki/Evidence-based_medicine.
(6 NOI) Federal Register 65, no. 95 (16 May 2000): Proposed Rules, 31124–31129.
(7 Registry User's Guide) http://www.effectivehealthcare.ahrq.gov/repFiles/PatOutcomes.pdf.
(8 Stark) Registry Studies for Medical Devices - Workshop (Mar 2010)
(9 CMRI) https://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=228&ver=16&NcaName=Magnetic+Resonance+Imaging+(MRI)&bc=gQAAAAAAIAAA&.
(10 Clark) Device Case Studies for Reimbursement Codes (Nov 2008).
(11 AMA & CPT Codes) http://www.ama-assn.org/ama/pub/physician-resources/solutions-managing-your-practice/coding-billing-insurance/cpt/cpt-process-faq/code-becomes-cpt.page.
(12 ICD-9) https://www.cms.gov/ICD9ProviderDiagnosticCodes/03_meetings.asp
(13 Level II) https://www.cms.gov/MedHCPCSGenInfo/Downloads/2012HCPCSApplication.pdf
(14 CTI) https://www.cms.gov/CouncilonTechInnov/01_overview.asp
(15 CED) http://www.cms.gov/coverage/download/guidanceced.pdf
(16 Innovator's Guide) https://www.cms.gov/CouncilonTechInnov/Downloads/InnovatorsGuide5_10_10.pdf

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc

Getting to First-in-Man Studies

Last month I had the opportunity to attend the CRT2011 meetings in Washington, DC. My purpose was to report on the March 1 "Workshop with the FDA" on device development in the US. My whitepaper today is to combine the cardiovascular message from "Workshop with the FDA" with significant findings published by AdvaMed in a November 2010 publication titled "FDA Impact on US Medical Technology Innovation." I hope to take a deeper look into the why behind the what, and then hopefully propose a way forward.

The Device Development 'Ecosystem'
When I talk about innovation, I am referring to either the conception and invention of new devices or to incremental improvements to existing devices. When I talk about development, I am referring to the bench, animal safety, pre-clinical and clinical studies that occurs before FDA clearance or approval or EU certification. When I use the adjective "clinical" in this paper, I am referring to human studies. By the way, the 'ecosystem' is the new buzzword for global device development, including regulatory, economic, and resource availability effects.

  
While the US is still the leader in medical device innovation, development has largely fled to other continents. Most first-in-man studies are done in Europe, Asia, Latin or South America. The reasons are a ready patient population, modern hospital facilities, and English-speaking physicians trained in Western medicine and good clinical practices.

But all of this begs the question, how is it that it is easier to get first-in-man trials approved in countries outside the US?

First-in-Man Approval in the US
In the States, first-in-man trials require the same review process as any other clinical trial, which means you must get an IDE from FDA if the device is significant risk. While FDA reports an average of 27 days to get IDE approval from time of IDE submission, and six months if you count from first communication, Advanced reports an average of 14 months to get an IDE approval from the time of first communication with FDA. The long lead-time results in costs and delayed revenue stream that venture capital firms are becoming unwilling to fund.

  
First-in-Man Approval in the EU
In many European countries the Ethics Committees (ECs) have the real control over approval for clinical trials; the National Authority is only notified of the trial's initiation but doesn't take an active review role. The Notified Body serves as the inspection arm and reviews certification sometime after the device is commercialized. This means the level of review for first-in-man studies rests in the hands of the Ethics Committees, which are usually local and most certainly not funded or trained to the level of FDA.

I can't find any figures for the time required from first EC submission to initiating the first-in-man study, but AdvaMed reports that a 510k-level device requires an average of only seven months to certification. When you compare the benefits of earlier revenue stream with the inconvenience of implementing studies on the other side of the ocean, it is small wonder that American manufacturers have moved their development process to Europe.

 

The Global Harmonization Task Force
As an aside, the Global Harmonization Task Force (GHTF) has attempted to close the gap between continents but it lacks regulatory teeth. Its documents are written with more hope than how-to, (Medical devices should be designed and manufactured in such a way that...they will not compromise the clinical condition or safety of the patients....), and an Australian report says GHTF is closing shop and will reopen as "regulators only."

The Flight of Device Development
Both the speakers at CRT2011's Workshop and the report from AdvaMed draw a disturbing picture of the flight of medical device development to Europe. Sean M Salmon of Medtronic (VP and General Manager, Coronary and Peripheral) said he does 95% of his clinical trials outside the US, "why bother with FDA?" He acknowledged that US investigators feel left out and that he, too, is frustrated with the US system. But exceptional competencies exist around the world and there is no reason to restrict clinical studies to the US.

As device development moved to Europe and to other countries, US investigators fall increasingly behind the curve. One trend is the development of international relationships between US and outside-US hospitals (example) whereby American physicians can participate in international clinical trials by practicing outside the country.

So if manufacturers have found a way to go to Europe and elsewhere, and investigators are finding a way to go to Europe and elsewhere, where does that leave the American patient? According to the Medical Tourism Association, medical tourism is one of the fastest growing industries within healthcare. Traveling to another country to receive healthcare is the pathway of choice for many Americans seeking leading-edge care. Many insurance companies, such as Aetna, the Blues, WellPoint, and others, have implemented medical tourism pilot programs to support such care.

The workshop with the FDA can be summarized in a few simple statements:
[1] Device development has moved to Europe.
[2] US investigators are following.
[3] Device availability is delayed two-to-five years in the US.
[4] Medicare reimbursement doesn't necessarily follow FDA clearance/approval.
[5] Patients are following the new technologies through medical tourism.
[6] As development leaves the US, innovation and jobs will follow.
[7] The device industry is struggling under Healthcare Reform's federal excise tax on sales.

FDA's Response
Next at the workshop it was FDA's turn to speak. Dr. Ashley Boam (Branch Chief, Interventional Cardiology Devices, CDRH, FDA) summed FDA's position up simply: "Bring us better pre-clinical data."

Pre-clinical Strategies
In addition to ISO 10993 biocompatibility testing, preclinical animal testing to investigate potential harms to humans before doing first-in-man studies may be necessary. Such testing is often done in large animals in order to mimic clinical use of the device. You need to select a species whose anatomy can receive the device or provide reasonable feedback regarding human use.

There is no single, prescribed protocol for preclinical studies. Instead the intended use of the device is reproduced as best as possible. The potential harms from the device are identified from the literature or prior experience, including biological harms, mechanical harms, electromagnetic harms, software harms, harms from human error, or harms from any other source. Finally a protocol is developed to investigate the device's safety and performance. The species of animal, sample size, endpoints and pathology must all be justified. The protocol should be approved by an Animal Care and Use Committee and implemented in conformance with ISO 10993-11 "Systemic toxicity" Section 6. FDA favors the involvement of an experienced toxicologist in the development of the protocol and the final report.

For example, an embolization system was evaluated in a rabbit model, a thrombectomy device was evaluated in porcine whose arteries had been injected with fribrin-laden thrombi, a robotic spinal surgical system was evaluated in a porcine model, but I could find no accepted animal model for evaluating joint surface repair or osteonecrosis.

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CDG Can Help with Pre-Clinical Strategies

Dr. Dan McLain, convener of ISO 10993-11, is available to assist with pre-clinical strategies for your device. Our style is to work collaboratively with a point-person on your side so that you are involved in the process every step of the way. Phone or email us at 773-489-5721 or cdginc@clinicaldevice.com.

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Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc

ISO 14155 (2011) Good Clinical Practices for Medical Devices Is Here

It's time to update your procedures!
Coming into force very, very soon.

The International Standards Organization (ISO) has finally done it. Earlier this week they published the good clinical practices for medical device clinical investigations: ISO 14155 "Clinical investigations of medical devices in human subjects—good clinical practices" (2011). You can buy your very own copy at www.iso.org for 158 Swiss francs, search for 14155.

 

Once the standard is harmonized via publication in the Official Journal of the European Union it comes into force immediately; it will be tough, so you should start updating your procedures for European studies now. What's the "proof" that enforcement is immediate? And what will it mean for your study? Read on.

No phase-in period—the tedious proof
You can take my word for it, or you can follow the tedious proof presented in the next paragraphs to convince yourself about the enforcement date. We will look only at the Medical Device Directive (MDD); you can follow the same logic for the Active Implantable Medical Device (AIMD) directive on your own.

Annex ZA of the standard
Annes ZA of the standard states: "Once this standard is cited in the Official Journal of the European Communities under that Directive and has been implemented as a national standard in at least one Member State, compliance with the normative clauses of this standard confers, within the limits of the scope of this standard, a presumption of conformity with the relevant Essential Requirements 6a of that Directive and associated EFTA regulations."

Which means—in American English—once the standard is cited in the Official Journal, you will meet the Essential Requirements of the MDD for clinical investigations if you conform to the standard.

Essential Requirements of the MDD
Turning our attention to the MDD, in Article 3 we read:

"Article 3
Essential requirements
The devices must meet the essential requirements set out in Annex I which apply to them, taking account of the intended purpose of the devices concerned.”

And in Article 4 of the MDD paragraph 2, we read:

“Article 4
2. Member States shall not create any obstacle to:
— devices intended for clinical investigation being made available to medical practitioners or authorized persons for that purpose if they meet the conditions laid down in Article 15 and in Annex VIII,”

And in Article 5 of the MDD, paragraph 1, we read:

“Article 5
Reference to standards
1. Member States shall presume compliance with the essential requirements referred to in Article 3 in respect of devices which are in conformity with the relevant national standards adopted pursuant to the harmonized standards the references of which have been publishes [sic, published] in the Official Journal of the European Communities; Member States shall publish the references of such national standards.”

Harmonized standards
You can check the MDD at ec.Europa.eu to see if the standard has been harmonized to the directive. Scroll down on the page to see the long list of harmonized standards. As of today, the 2003 versions of the clinical investigation standards are still in force. I'm told it takes 5-6 months before the a new ISO standard is cited in the Official Journal and harmonized to the directive.

 
 

Frequently asked questions—my guess at the answers
Your Notified Body is your final arbiter for enforcement of the new ISO standard for ongoing studies. A good rule of thumb is that the standard applies to your investigation from the time it is harmonized and going forward, but does not apply retrospectively to activities that are already completed.

[1] When the standard comes into force, what happens to clinical investigations that are currently enrolling?

The new rules will apply to the remainder of the investigation. This means investigators and study staff must to be trained to the new standard and their heavier responsibilities, new data forms for collecting device deficiencies should be created, and the like. It may be useful to develop an educational pack for the Ethics Committees.

[2] When the standard comes into force, what happens to clinical investigations that are completed (last subject is out) and I am analyzing the data?

The final report, i.e. clinical investigation report, should follow the format and content of the standard.

[3] When the standard comes into force, what happens to clinical investigations I am setting up? Let's say I have investigators and sites, and I have EC approval, but I have not yet enrolled the first subject?

Your clinical investigation procedures and quality management system should be updated now to meet the intense requirements of the new standard. Because you haven't enrolled subjects yet, you can expect to redo most of your administrative set-up if it wasn't done in conformance to the new standard.

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CDG Can Update Your Procedures

CDG was actively involved in writing ISO 14155 (2011). We understand the intention behind the words and can help explain standards-speak in a way you can understand. We can review your procedures, provide recommendations to bring them into conformance, or write additional procedures if needed.

Our style is to work collaboratively with a point-person on your side so that you are involved in the process every step of the way. Phone or email us at 773-489-5721 or cdginc@clinicaldevice.com.

 

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc

CDRH's 510(k) Working Group Preliminary Report—Findings 6 & 7

 Valuable, not-commonly-known information

In August 2010, CDRH's 510(k) Working Group published a preliminary report consisting of more than 60 recommendations grouped under seven findings aimed at improving the Center's effectiveness in implementing its missions. In our cycle of whitepapers, Kathleen and I have been reviewing the findings and recommendations, offering our observations of how they will affect the industry, and making alternative recommendations when we think we have a better idea.

Last week FDA issued its plans for Next Steps, but before we look at them I'd like to make some comments on Findings 6 and 7 because we uncovered some valuable, yet not-commonly-known information.

To recap, the first five findings were:
[1] There is insufficient clarity with respect to the definition of "substantial equivalence".
[2] CDRH's current practice allows for the use of some types of predicates that may not be appropriate.
[3] The de novo pathway is important and has not been optimally used across the Center.
[4] It is challenging for reviewers to obtain the information they need to make well-supported clearance decisions.
[5] CDRH's knowledge management infrastructure is limited.

In this final whitepaper we will look at Findings 6 and 7.

Finding 6: Variations in the expertise, experience, and training of reviewers and managers, including third-party reviewers, may contribute to inconsistency or uncertainty in 510(k) decision making.

More than 30% of reviewers, 31.5% to be exact, have less than two years experience; which means that one-third of the 510(k)s submitted to FDA will be reviewed by people with little agency history in their heads. One former high-level manager from CDRH advised me to study the preambles to every regulation. Preambles have legal standing, but most reviewers have never read them. I once asked a mid-level manager from CDRH BiMo how they could give a warning letter to a sponsor over a consent form that had been approved by an IDE reviewer; she scoffed and said: "Reviewers don't have time to read all that stuff."

 

[1] Reviewer Memoranda
Reviewers prepare an internal "review memo" for every 510(k) reviewed. The review memo documents the rationale of their decision. The Working Group Report states that less experienced reviewers write lengthier review memos, which are presumably more efficient. Something unexplained seems to happen with reviewers with more than ten years' experience; their highest percentage falls into an "unknown page count" column. (See Table 5.9 of the Report.)

 

Working Group Recommendations
The Working Group did not make recommendatations specific to review memos.

CDG recommends the very existence of review memos be more widely publicized. A careful search of the FDA website, Device Advice, and Google turned up very litle information about review memos. In fact, the only information I found concerned the 510(k) Quality Review Program, which states that a random selection of 510(k)s will be selected for review each quarter. A phone call to CDRH's Office of Device Evaluation gleaned the information that an internal review memo is written by the reviewer for every 510(k) reviewed, the memos are not generally offered to the submitter, and are available under the Freedom of Information Act. A call to FOI Services Inc (301-975-9400) confirmed this information, and copies of review memos for specific 510(k)s can be obtained through their office.

The review memo is of vital importance in gaining insight into the reviewer's thinking. Because the memos are available under Freedom of Information, why not make them available in the 510(k) database so that everyone can see them without making an independent FOI request? It would contribute to better submissions and more consistent reviews.

In addition, if your 510(k) submission was not cleared or received an NSE decision, the review memo should automatically be included in the FDA letter to the submitter.

[2] Third-Party Review
Class I and Class II 510(k) that do not require clinical data may go through a pre-review by an accredited third-party. While data show that submissions that have gone through pre-review tend to go through the final FDA review faster, there are no data to show if the total review process (pre-review plus FDA review) is longer or shorter. Concerns have been raised about the quality and consistency of third-party reviews.

Working Group Recommendations
The Working Group recommends regular evaluation of what devices are eligible for third-party review and that the agency enhance its third-party training programs.

CDG agrees. The third-party review program should be promptly expanded as planned in the Next Steps. Kathleen's personal experience with third-party reviewers has been extremely positive. She recommends shopping for companies who have reviewer's experienced in your type of product, checking their schedule for reviewing, and assessing the cost of the review. Typically the reviewer willl require less than a month to give tentative approval (or discuss deficiencies) for the submission. In Kathleen's experience FDA has always concurred.

[3] Enhance reviewer training
The Working Group recommends that reviewer training, professional development, and knowledge-sharing be enhanced.

CDG agrees. A lack of reviewer experience has serious consequences for manufacturers. Submissions are not reviewed consistently, reviewers may not have the scientific training to adequately review the submission, decisions may be delayed, review decisions may be inadequately documented, unnecessary or even outdated or inappropriate testing may be requested. In one situation, the reviewer of an IVD submission utilizing de-identified data asked the submitter to obtain additional information from the clinical subjects—an illegality because it would violate privacy rules, as well as impossible because the subject's identity was not known. In the case of the IDE approved informed consent form, BiMo nevertheless issued a warning letter for alleged deficiences.

Finding 7: CDRH does not currently have an adequate mechanism to regularly assess the quality, consistency, and effectiveness of the 510(k) program.

CDRH's primary tool for assessing the quality of 510(k) reviews is its 510(k) Quality Review Program. Through this program, managers in ODE and OIVD assess a sample of review memoranda on a quarterly basis. A standardized checklist is used to evaluate the completeness of each review memorandum, but not the adequacy or appropriateness of the reviewer’s decision making rationale and explanation.

Further, although CDRH collects information on device performance in the postmarket setting, important limitations, including the inability to consistently link postmarket events to specific 510(k)s, make this information, in isolation, an unreliable measure of program effectiveness.

Working Group Recommendatons
The Working Group recommended that CDRH develop metrics to continuously assess the quality, consistency, and effectiveness of the 510(k) program, to periodically audit 510(k) review decisions, and to measure the effect of any actions taken to improve the program.

CDG agrees and is hopeful that such information will be made publicly available in ODE's annual reports. Submitters can only increase the quality of their submissions if they have examples to work from.

CDG Can Write Your 510(k)

CDG's extensive Network Staff has expertise in writing 510(k)s in a wide variety of therapeutic, management, or diagnostic areas. My co-author, Kathleen Johnson is a regulatory consultant with more than 10 years experience in medical devices. CDG has capabilities in regulatory submissions, clinical research, toxicology, biostatistics, information research, medical writing, design control—we focus exclusively on medical device pre-approval issues.

Our style is to work collaboratively with a point-person on your side so that you are involved in the process every step of the way. Phone or email us at 773-489-5721 or cdginc@clinicaldevice.com.

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc

European Medical Device Update

A Few Items of Note about Device Regulation in the European Union

Life keeps moving along in Europe in spite of the snow and closed airports. Here are three important medical device regulatory issues you'll want to address in the new year.

[1] No phase in period for ISO 14155 "Clinical investigation of medical devices in human subjects—good clinical practices"
If the stars align, Jupiter stays in the heavens, and my cat stops catching birds, ISO 14155 may be published in the first quarter of 2011. But don't wait around for the big event. Implementation will be immediate and there is no phase in period!

The convener recommends all sponsors start updating their clinical investigation procedures now. However, updating your procedures is a little bit difficult because the final draft of the standard is not available for purchase on the www.iso.org website. ISO.org lists the standard as being under publication (stage 60.00) but provides no means to add it to your shopping cart.

 

The same is true for the Association for the Advancement of Medical Instrumentation at www.aami.org, which has inexplicably truncated the title to "Clinical investigation of medical devices for human subjects" and left off the declaration of "good clinical practices". AAMI claims identical equivalency to ISO 14155/Ed.3 (edition 3?), and states the draft is not available 'outside of committee'.

CDG can update your clinical procedures to ISO/FDIS 14155

Clinical Device Group is a corporate member of AAMI, a member of ISO TC 194, and has access to the final draft versions of ISO/FDIS 14155 "Clinical investigation of medical devices for human subjects—good clinical practices". While we can't provide you with a copy of the unreleased document, we can review your existing procedures and make recommendations to bring them into conformance. Our style is to work collaboratively with point-person on your side so that you are involved in the process every step of the way. Phone or email us at 773-489-5706 or cdginc@clinicaldevice.com.

 If you don't work for one of the thirty or so firms who pay corporate dues to AAMI, are members of TC 194, and have access to the final draft standard, you will have to figure out another game plan. You might consider hiring a CRO with access to the final draft to update your procedures for you.

2] MEDDEV 2.7/3 Serious adverse event reporting under the amended Directives
The European Commission published MEDDEV 2.7/3 "Serious Adverse Event Reporting under 90/385/EEC and 93/42/EEC" in December 2010. Although the guidance is voluntary, you are strongly urged to follow it. The guidance uses the ISO/FDIS 14155 definitions of adverse events and effects, and recommends that all serious adverse events (SAEs), device deficiencies that might lead to SAEs, and any new findings regarding existing SAEs, be reported to every National Competent Authority (NCA) in which the investigation is being conducted.

Two categories of SAEs
The guidance takes the odd approach of dividing SAEs into two categories: a) those that require prompt remedial action, and b) those that do not.

SAEs that require prompt remedial action to mitigate an imminent risk of death, serious injury, or serious illness should be reported immediately but no more than 2 (two) calendar days to the NCAs using the Reporting Form provided in the guidance Appendix. SAEs that do not require prompt remedial action should be reported no more than 7 (seven) calendar days. The MEDDEV 2.7/3 guidance and an Excel spreadsheet of the Reporting Form are provided on CDG's website.

Observations
A serious adverse event that occurs at a US site should be reported to every European NCA in which the investigation is also being conducted. CDG recommends that investigations in the US and EU be administered and managed as separate studies because: 1) it is difficult to meet the reporting requirements of two different regulatory entities in the same investigation, and 2) it is difficult to justify pooling data given the differences in medical practice. Patients in countries with socialized medicine tend to be farther along in the disease process before receiving medical care than patients from countries with for-profit medical care.

The guidance makes no mention of reporting serious adverse events to Ethical Committees. It doesn't discuss sharing of data between National Competent Authorities. It doesn't address setting up a European database of serious adverse events. And it doesn't address making the SAE reports available to the public. As much as we have complained about a lack of transparency and organization at FDA in recent whitepapers, Europe has a long way to go before it catches up.

[3] MEDDEV 2.7/4 Clinical investigations: A guide for manufacturers and Notified Bodies
The European Commission also published MEDDEV 2.7/4 "Guidelines on Clinical Investigation: A Guide for Manufacturers and Notified Bodies" in December 2010. Again the guideline is not legally binding, but it reflects the thinking of the European Commission and what manufacturers can reasonably expect from their Notified Bodies.

Distinctions
The guideline tries to clarify the European distinctions between clinical data, clinical evaluation [reports], and clinical evidence. The logic is not obvious, so I've designed a graphic to help sort it out.

 

Clinical data are numbers, values, measurements, and the like, taken from the literature, sponsored clinical investigations, and other reports such as complaint history files and risk management systems.

Clinical data are assessed, analyzed, and written up in clinical evaluation reports.

Clinical evidence is both the original clinical data (numbers and values) and the clinical evaluation report.

If the clinical evidence is sufficient to establish the safety and performance of a device for its intended use, then the manufacturer may declare conformity to the essential requirements and proceed to market the device. If the clinical evidence is insufficient to establish safety and performance, the manufacturer may withdraw the claim or proceed to a new clinical trial in an effort to generate data to substantiate the claim.

Differences between US and EU
The fundamentals of good clinical practices haven't changed and are not much different between the US and EU. The new ISO 14155 standard was written to harmonize as close as possible with the existing ICH-GCPs; so if you are an experienced clinical research professional there will be no surprises. But there are some differences in implementation.

The first difference is the heavy level of adverse event reporting in Europe. Even for European Class I and IIa devices, all adverse events are reportable to sponsors, Ethics Committees, and NCAs; and all serious adverse events—device related or not—are reportable to NCAs within 2-7 days. In the States, for significant risk devices, only adverse device effects are reportable to sponsors, IRBs, and FDA (unless FDA requires more for a particular investigation); and for non-significant risk devices, adverse device effects are only reportable to sponsors and IRBs.

The second difference will be the increased emphasis on risk management in the clinical investigation process and figuring out how to apply ISO 14971 "Application of risk management to medical devices" to clinical investigations.

Got feedback?
If you have comments, disagreements, or additional information, please post them below. I look forward to hearing from you.

Happy New Year,

Nancy J Stark, PhD
President, Clinical Device Group Inc
cdginc@clinicaldevice.com

 

 

CDRH's 510k Working Group Preliminary Report: Finding 5

A GLIMPSE AT THE FUTURE?
A Cycle of 510(k) Whitepapers by Nancy J Stark and Kathleen Johnson

In August 2010, CDRH's 510(k) Working Group published a preliminary report consisting of more than 60 recommendations grouped under seven findings aimed at improving the Center's effectiveness in implementing its missions. Will the recommendations work? Do they comprise a forward-thinking strategic plan for the device industry? Herein you'll find CDG's summation of Finding 3 and part of Finding 4, along with our opinions of their worth.

Finding 5: CDRH's knowledge management infrastructure is limited

Neither Center staff nor 510(k) submitters have access to meaningful information
The only comprehensive electronic source of non-public information on prior 510(k) reviews available to Center staff is a database of archived image files. The database is searchable only by 510(k) number. To find information within each file, staff must conduct a labor-intensive, file-by-file text search. Without looking through each file individually, it is impossible to determine what predicate(s) the reviewer used as the basis for a substantial equivalence determination, and what the rationale for the decision was. Moreover, archived files contain varied levels of detail. Older 510(k) submissions and review memoranda are inconsistent in format and content, and many of them are handwritten.

[1] Enhanced 510k database needed
The Working Group recommends that both internal and public information systems be enhanced.

CDG agrees and further suggests the databases be made available through PubMed, Embase, or even Google where the ability to limit date ranges, use 'not' operators, turn on keyword explosion, use fuzzy logic, and use sophisticated text-search tools are available. Furthermore, the database in its entirety should be downloadable to Excel. The Summaries of Safety and Effectiveness or 510(k)s themselves should be keyworded by K number, product code, predicates, generic and brand names to allow for 'family trees' or 510k pedigrees to be constructed. The information should be available all the way back to 1976, and not stop at 2002.

CDG can write your 510(k)
CDG's extensive Network Staff has expertise in writing 510(k)s in a wide variety of therapeutic, management, or diagnostic areas. My co-author, Kathleen Johnson is a regulatory consultant with more than 10 years experience in medical devices. CDG has capabilities in regulatory submissions, clinical research, toxicology, biostatistics, information research, medical writing, design control—we focus exclusively on medical device pre-approval issues.

Our style is to work collaboratively with a point-person on your side so that you are involved in the process every step of the way. Phone or email us at 773-489-5721 or cdginc@clinicaldevice.com.

[2] Product Codes, also known as classification numbers
Product codes are the underpinning for CDRH’s information management systems. They are the primary tool for organizing medical device information in CDRH’s databases, and staff across the Center rely on product codes in their day-to-day work. Product codes are used for tracking and analysis of medical device data across a device’s total product life cycle, including information from premarket submissions, adverse event reports, device recalls, inspections, and compliance actions. Review staff and 510(k) submitters use product code searches to identify and obtain information about potential predicate devices. Product codes were intended to provide more granular distinctions than the general descriptive language provided in the classification regulations. However, inconsistencies in the way product codes are assigned make it difficult to access meaningful device information.

The origin of "product codes" is so old even the Working Group could not give it an accurate reference; a day of research revealed the term "classification number" on FDA Form 2892, which was introduced in 1977 in 21 CFR 807.26, somehow transformed itself into the term "product code" (for a three letter, non-numeric code) at some point in time.

Working Group Recommendations
The Working Group recommends that the agency develop procedures for assigning product codes consistently and that special attention be given to IVD multiplex devices.

CDG agrees and suggests the search engine for product codes be improved. At this time, in order to find a predicate device you can: 1) search keywords in the classification database (simple search) to get a list of product codes and regulation numbers that match your keywords, 2) then search on the product code in the 510(k) database to find possible predicates for your new device. But this method is laborious, time-consuming, and the list that results may not contain good matches for your device. Furthermore, if your device is made of multiple components you will have to do a separate search for each component. And the list does not go back to 1976, so a comprehensive search is not possible. We also suggest that the device listing Form FDA 2892 ask for a product code rather than a classification number to dispel confusion, and that a history of the relationship between the two terms be clarified.

[3] 510(k) Databases
The 510(k) database is not easily searchable for either reviewers or submitters. Lacking a reliable source of accurate information, 510(k) submitters may be forced to look at how the predicate is advertised, which does not necessarily reflect the intended use for which it was cleared. Once cleared, device 510(k) are not accompanied by a revewer-prepared Decision Summary or a reviewer-prepared Summary Basis of Approval, as are IVD 510(k)s or pharmaceuticals. These Summaries are written by the FDA reviewer and capture the thought process and rationale for clearance.

 The data are from page 39 of the Working Group Preliminary Report

 
Working Group Recommendations
The Working Group recommends that CDRH develop a publicly available, easily searchable database that includes, for each cleared device, a verified 510(k) summary, photographs and schematics of the device (to the extent that they do not contain proprietary information), and information showing how cleared 510(k)s relate to each other and identifying the premarket submission that provided the original data or validation for a particular product type.

CDG believes that if a decently searchable 510(k) database were made available to submitters, the quality of submissions and appropriateness of predicates would improve automatically and the time to clearance would decrease. The database should go as far back as 1976 to facilate comprehensive searches. No further changes or requirements should be made until a functional seach engine is developed.

CDG further recommends that a reviewer-prepared Decision Summary be prepared for every cleared 510(k) as an enhancement to the 510(k) Quality Review Program (I96-1). It should be made available to the public, along with the company-prepared 510(k) Statement or Summary. This would enhance quality in 510(k) submissions and consistency in 510(k) clearances.

[4] Final Device Labeling
One frustration for FDA is that final device labeling and updates to labeling are not routinely reviewed; hence labeling may be inconsistent with, or over-interpret, cleared indications.

Working Group Recommendatons
The Working Group recommended the agency explore the requiring manufacturers to submit final device labeling to FDA by the time of clearance or within a reasonable period of time after clearance, and also to provide regular, periodic updates to device labeling.

CDG's concern is that requiring final labeling before a 510(k) is cleared would merely add to the timeframe for clearance. Annually updating device labeling—when taken together with the previous recommendations for annual updates for device modifications and the recommendation that all scientific information be included in the original submission, regardless of whether or not it supports an argument of substantial equivalence—is tantamount to requiring an annual 510(k) supplement similar to that required for PMAs. It is unduly burdensome for manufacturers of 510(k) devices and an already overburdened FDA staff could not handle the additional data.

We suggest that FDA update the 1997 guidance document "Deciding When to Submit a 510(k) for a Change to an Existing Device" and make available an online webcast to educate manufacturers about its contents.

[5] 510(k) Ownership
CDRH’s databases rarely reflect changes in 510(k) ownership that occur after clearance, largely because the Center is not typically notified of transfers of ownership.

Working Group Recommendations
The Working Group recommends the agency develop guidance and regulations regarding appropriate documentation of transfers of 510(k) ownership. The Center should update its 510(k) database in a timely manner when a transfer of ownership occurs. CDG, as well as a majority of public comments, support the recommendation.

CDRH Missions
The Center for Devices and Regulatory Health has two important missions: 1) to protect the public health, and 2) to foster medical device innovation. Their difficult job is to keep these missions in balance, never compromising one in favor of the other. Do you have the original citation for fostering medical innovation?

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc

CDRH's 510(k) Working Group—Finding 4

A GLIMPSE OF THE FUTURE?
A Cycle of 510(k) Whitepapers by Nancy J Stark and Kathleen Johnson

The Center for Devices and Regulatory Health has two important missions: 1) to protect the public health, and 2) to foster medical device innovation. Their difficult job is to keep these missions in balance, never compromising one in favor of the other.

In August 2010, CDRH's 510(k) Working Group published a preliminary report consisting of more than 60 recommendations grouped under seven findings aimed at improving the Center's effectiveness in implementing its missions. Will the recommendations work? Do they comprise a forward-thinking strategic plan for the device industry? Herein you'll find CDG's summation of Finding 3 and part of Finding 4, along with our opinions of their worth. If you wish to comment, please do so below.

Finding 4: It is challenging for reviewers to obtain the information it needs to make well-supported clearance decisions

[5] Improper use of recognized standards—require a summary of testing
Section 514(c)(1) of the Act describes the possibility of using, as part of a 510(k) submission, consensus standards that have been entirely or partially recognized by FDA. This section states, “[FDA] shall, by publication in the Federal Register, recognize all or part of an appropriate standard established by a nationally or internationally recognized standard development organization for which a person may submit a declaration of conformity in order to meet a premarket submission requirement or other requirement under this Act to which such standard is applicable.”

Working Group Issues
The problems are that: 1) a device may raise questions of safety and performance not addressed by the consensus standard; the standard provides only partial evidence of substantial equivalence, 2) submitters may not use the most current version of a standard, they may not be able to determine which sections of the standards are recognized and which are not (you must turn to the supplemental information sheets), and 3) submitters do not always indicate how they have used the standard or deviated from the standard.

CDG Comments: The recognized version of a standard, not the current version, should be used. The 510(k) Manual should be updated to discuss the proper use of consensus standards and the "Standards Data Report Form for 510(k)s" should be modified to provide a place for summary information and all other relevant information FDA requires.

CDG can write your 510(k)

CDG's extensive Network Staff has expertise in writing 510(k)s in a wide variety of therapeutic, management, or diagnostic areas. My co-author, Kathleen Johnson is a regulatory consultant with more than 10 years experience in medical devices. CDG has capabilities in regulatory submissions, clinical research, toxicology, biostatistics, information research, medical writing, design control—we focus exclusively on medical device pre-approval issues.

Our style is to work collaboratively with a point-person on your side so that you are involved in the process every step of the way. Phone or email us at 773-489-5721 or cdginc@clinicaldevice.com.

[6] Incomplete information—how much is enough?
Current regulations require 510(k) submissions to provide "data to support the statement" regarding substantial equivalence to a predicate device. Under PMA regulations, PMA applications are explicitly required to contain a summary of all information known concerning the safety and/or effectivenes of the device under review. FDA's concern is that submissions may contain biased information, including only clinical or scientific information that supports device equivalency.

Working Group recommendations
The Working Group recommends that 21 CFR 807.87 be revised to explicitly require 510(k) submitters to provide a list and brief description of all scientific information regarding the safety and/or effectiveness of a new device known to or that should be reasonably known to the submitter.

CDG comments: The recommendation to review all available literature is not in keeping with the original intention of the Act, which was to demonstrate substantial equivalence to a predicate. It sounds like a Clinical Evaluation Report for every medical device in Europe. The result could inundate FDA with so much information that an already stressed Agency would increase its review times rather than become more efficient.

Summarizing data generated by other parties on similar, but not equivalent devices, is not helpful; summarizing data generated by other parties on equivalent devices but dissimilar test methods is not helpful. Much information is developed using early design or prototype devices. Would the recommendation require a review of every document in the design history file and before? It has the feel of a PMA, where safety and performance are established de novo.

Listen to Experts Janice Hogan and Yarmela Pavlovic
Discuss "The Successful 510(k)"

Listen to experts Janice Hogan, Esq and Yarmela Pavlovic, Esq. present the whys and hows of crafting a successful 510(k) on CD or OnDemand and take advantage of their vast experience. Their detailed and thorough presentation covers: 1) the legal framework, 2) finding predicates, 3) chosing the right claim, introducing new features, 4) assessing data requirements, 5) software and combination products, 6) dealing with a not-substantially equivalent (NSE) determination, 7) handling device modifications, and 8) seeing the 510(k) from the reviewers perspective. You'll receive the slide deck, video/audio recording, and links to important guidances. Order here.

[7] Type and level of evidence needed
The reviewer's first step is to determine if the device and predicate have the same intended use. However, once this is done, most devices have either different indications for use and/or different technological characteristics than the predicate, and FDA may want data to show that any differences have not altered the intended use or significantly affected the safety and/or effectiveness of the device. In most cases data from bench and/or animal testing is sufficient to complete the argument of safety and effectiveness, but in some cases the Agency wants additional data.

Working Group recommendations
The Working Group recommends the agency develop guidance defining a subset of devices, i.e. Class IIb devices, for which clinical information, manufacturing information, or post-marketing information would be typically necessary.

CDG has already stated that it disagrees with defining Class IIa and Class IIb devices because it will lead to confusion with European Class IIa and IIb device classification schemes. If clinical, manufacturing, or post-market information is necessary to successfully argue safety and effectiveness, the agency can address this via a "Super" 510(k). As prevsiouly stated, the regulation numbers of devices and the required information for Super 510(k)s should clearly defined; the information requirements cannot change with each submission.

[8] Clinical information
The Working Group acknowledges there is common misunderstanding as to what constitutes clinical data. Yet within the space of four paragraphs on pages 76-77 of the report the Working group refers to "clinical information", "clinical data", "clinical evidence", "clinical investigation", and "clinical study". According to CDRH staff, submitters sometimes cite the definition of “valid scientific evidence” together with the “least burdensome” provisions of the Act, claiming that it is sufficient for them to provide any type or level of evidence that meets the definition of “valid scientific evidence” with the lowest possible level of burden, even if such evidence fails to provide "reasonable assurance" of safety and effectiveness.

 

 
Working Group recommendations
The Working Group recommends a “Class IIb” guidance provide greater clarity regarding the circumstances in which the agency will request clinical data in support of a 510(k), what type and level of clinical data are adequate to support clearance, and to define clinical data. Would this mean that all IVD 510(k)s are Class IIb?

CDG recognizes there are situations in which new clinical data may be necessary to establish substantial equivalence and demonstrate safety and effectiveness.

For the most part, however, substantial equivalence, safety, and performance can be clearly established with valid scientific evidence obtained from bench and animal data. Needlessly requesting new human clinical data is unethical. All clinical trials expose human subjects to risk by their very definition. It is not that not conducting a clinical trial should be justified, but that the very act of conducting a clinical trial should be justified.

By needlessly raising the bar to 510(k) clearance, FDA neglects is obligation to foster medical device innovation.

With regard to clinical information, FDA should harmonize its definitions of clinical information with Europe and GHTF so that communication between submitters and reviewers can be clear. In the Europe and GHTF world clinical information is data from the literature, research in humans is a clinical investigation (study or trial may be used colloquially), clinical evaluations are reviews of clinical information and clinical investigations and the risk management system altogether.

[9] Postmarket information
CDRH feels that for certain devices, including novel or particularly complex technologies, it is not feasible to conduct a large-scale clinical trial prior to clearance [does this mean such devices are now cleared without adequate clinical data?] They feel it is necessary to collect additional data after clearance in order to better evaluate the safety and effectiveness of a device over a longer time period, or in a wider patient population.

CDRH has the authority to require postmarket surveillance studies (also called Section 522 studies) as a condition of 510(k) clearance for devices that are expected to have significant use in pediatric populations, but there is no explicit authority for CDRH to order Section 522 studies as a condition of premarket clearance in other situations.

Working Group recommendations
The Working Group recommends the Agency seek greater authority to require postmarket surveillance studies as a condition of clearance for certain devices.

CDG comments: The public health may benefit from postmarket registry studies for certain long-term use devices or devices with very long-lasting effects, however the decision to conduct such studies should be that of the manufacturer and not a condition for clearance.

The agency should continue to develop a unique device identification (UDI) system. There is a vast store of information collected everyday from Medicare billing records, Medicaid billing records, the Health Care Utilization Program (HCUP), and other public information sources, which will allow "real-world" anonymized data on device use and outcomes to be searched, sorted, and correlated.

[10] Manufacturing process information
Working Group recommendations
Because 37% of device recalls are associated with manufacturing problems, the Working Group recommends CDRH develop guidance to provide greater clarity regarding what situations may warrant the submission of manufacturing process information as part of a 510(k), and include a discussion of such information as part of its “class IIb” guidance. The Working Group further recommends the agency seek authority to withhold clearance on the basis of a failure to comply with good manufacturing practice requirements in certain situations.

CDG comments: There are situations, as with novel materials, when manufacturing process and design control information should be part of the 510(k) and that such situations should be addressed in a guidance.

A requirement to have evidence of a good manufacturing practice system in place prior to clearance moves the 510(k) process into the arena of a PMA. Many of the proposals by the Working Group blur the line between the 510(k) and PMA processes. The distinction is clear in the Act and should be honored by the Agency.

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc

 

CDRH's 510(k) Working Group—Findings 3 & 4a

A GLIMPSE OF THE FUTURE?
A Cycle of 510(k) Whitepapers by Nancy J Stark and
Kathleen Johnson

The Center for Devices and Regulatory Health has two important missions: 1) to protect the public health and 2) to foster medical device innovation. Their difficult job is to keep these missions in balance, never compromising one in favor of the other.

In August 2010, CDRH's 510(k) Working Group published a preliminary report consisting of more than 60 recommendations grouped under seven findings aimed at improving the Center's effectiveness in implementing its missions. Will the recommendations work? Do they comprise a forward-thinking strategic plan for the device industry? Herein you'll find CDG's summation of Finding 3 and part of Finding 4, along with our opinions of their worth. If you wish to comment, please do so at our blog.

 
Finding 3: the de novo pathtway is important and has not been optimally used across the Center.

The de novo process is an essential tool but difficult-to-use tool
The de novo classification process was established under FDAMA to allow for the 510(k) clearance of devices for which there is no predicate but whose risks do not warrant a PMA approach. The problem with the current system is that a device must first be classified as a Class III through a formal process. The issue is how to expedite classification.

The Working Group recommendation
CDRH reform its implementation of the de novo classification process to provide a practical, risk-based option that affords an appropriate level of review and regulatory control. While the number of de novo requests increases every year (there were 15 in 2009) the review process has become an incredible 2-3 years!

CDG Comments: We agree with the Working Group recommendation and further recommend that the Agency develop a separate de novo application which would include: 1) evidence of no predicate for the intended use and/or technology, 2) demonstration of low risk through design control and biological safety information, and 3) a mechanism for de novo meetings with the Agency. The application should be reviewed within 60 days of submission.

Typically CDRH develops device-specific guidance documents as special controls for de novo devices. CDRH should develop a single generic set of controls that could serve as the baseline. Device-specific guidelines can be added later, as needed.

This would give the Agency an avenue to either quickly classify a device as Class I or II via the de novo process or determine that the device is actually a Class III device.

 

Finding 4: It is challenging for reviewers to obtain the information it needs to make well-supported clearance decisions.

Class IIb Devices versus a "Big Mac" 510(k)
Working Group recommendations
The Working Group recommends creation of a new "class IIb" device classification.

CDG is baffled that the Working Group thinks a new "class IIb" classification is necessary or would even helpful to their obtaining sufficient levels of information about a device to make fully informed decisions.

First, it would add to global confusion. The European Union has a Class IIa and Class IIb device classification system and the EU Class IIb and US Class IIb are unnlikely to be the same. Because most companies do business globally, we should at least be creative enough to think of a new phrase.

And why not build on what we already have: a Special 510(k), Abbreviated 510(k), and Traditional 510(k). If we follow our existing pattern and instead create a new type of 510(k) called a "Super 510(k)" or "510(k) Plus." The Super 510(k) would describe additional information, over and above a traditional 510(k), that would be required for certain, significant-risk Class II devices. A new category of 510(k) can be structured to meet FDA needs, provide more options for the manufacturer, and avoid confusion with the world's second largest device market. We would like to see clear identification of the devices that require clearance under the "Super 510(k)" and defined requirements for data.

Device modifications: to report or not report?
Under current regulations, manufacturers are only required to submit new 510(k)s for device modifications when the modification "could significantly affect the safety or effectiveness of the device" or there has been a "major change or modification to the intended use of the device." The Agency has observed that minor, incremental modifications sometimes accrue to the point that safety, effectiveness, or intended use are affected. Also, there is concern that manufacturers misinterpret the regulation to mean that a new 510(k) is only necessary if a modification definitely does affect safety and/or effectiveness. There is also concern that manufacturers misinterpret the regulation to mean that a new 510(k) is only necessary if a modification could negatively affect safety and/or effectiveness.

When a 510(k) is submitted for a particular modification, CDRH must evaluate not only the effect of that modification itself on the device’s safety and effectiveness, but also the cumulative effect of any unreported modifications that preceded it. There is no explicit requirement for submitters to list the modifications that have been made since the last clearance. This can create challenges for review staff and may result in requests for additional information in the midst of a review.

Working Group recommendations
The Working Group recommends CDRH revise existing guidance to clarify what types of modifications do or do not warrant submission of a new 510(k), and, for those modifications that do warrant a new 510(k), what modifications are eligible for a Special 510(k) (i.e. declaration of conformity to design controls in lieu of providing detailed performance data to FDA as part of a 510(k).) The guidance should clarify that a new 510(k) is also required for changes that potentially could have a positive effect, because what was expected to have a positive impact may in fact create new risks that would not be detected without an adequate assessment.

Finally, the Working Group recommends that CDRH require each manufacturer to provide regular, periodic updates to the Center listing modifications made without 510(k) submission.

CDG comments: Modernizing guidances as to what type of modification requires a new 510(k) submission would be useful. When a 510(k) is submitted, it is reasonable to expect the submitter to identify all interim modifications in both design and/or labeling made since the previous submission.

Periodic modification reporting would result in a huge work overload for both manufacturers and reviewers. Neither party has the human or financial resources to manage regular reporting.

CDG can write your 510(k)

CDG's extensive Network Staff has expertise in writing 510(k)s in a wide variety of therapeutic, management, or diagnostic medical device areas. My co-author, Kathleen Johnson has more than 12 years experience in medical device regulatory affairs. CDG has capabilities in regulatory submissions, clinical research, toxicology, biostatistics, information research, medical writing, design control—we focus exclusively on medical device pre-approval issues.

Our style is to work collaboratively with a point-person on your side so that you are involved in the process every step of the way. Phone or email us at 773-489-5721 or cdginc@clinicaldevice.com.

Quality of submissions—crafting an argument
In this section the Working Group takes great pains to avoid stating outright that some submitters can't write: we do not make logical and scientifically developed arguments for safety and effectiveness (i.e. we don't apply the scientific method when structuring our arguments), we are disorganized, and we omit information that is clearly required.

CDRH reviewers state: "...information contained in the “Device Description” section of a 510(k) is often a general summary, and it frequently does not provide an adequate level of detail about the new device...." and "...or many 510(k)s, information provided in one section is inconsistent with information provided in another."

Working Group recommendations
The Working Group recommends the agency adopt the use of an "assurance case" framework for 510(k) submissions. An assurance case is defined as a documented body of evidence that provides a convincing and valid argument that a specified set of critical claims regarding a device's safety and performance are adequately justified. The definition parallels three steps of the scientific method.

 
Further, the Working Group recommends that both photographs and schematics be included with a submission, and that manufacturers retain at least one unit of a device and make it available to the agency for current or future reviews (e.g. when the device is cited as a predicate.)

CDG comments: FDA should update the 510(k) Manual (FDA publication 95-4158) and make it available under "guidances" in Device Advice. This document provides detailed guidance of what each section of a 510(k) should include. There is no need to develop yet another model, when a sufficient and familiar model already exists. Kathleen has used this manual as her guide in developing numerous, successfully cleared 510(k)s.

 
We searched for "510(k) Manual" in Device Advice and it isn't there. We searched for "510(k) Manual" in Google and it isn't there. Kathleen had a copy in her library so we could find the FDA publication number. When we searched for "FDA publication 95-4158" in Google we found a copy under FDA dockets. We were amazed that the 510(k) Manual was so difficult to find and not available at all under Device Advice.

FDA has a website for most of its databases, but the database for guidance documents—surely a key database for good 510(k) submissions—is not there. The website is called FDA Databases and you can see from the image above that there is no tab for guidances!

Part of the problem is that new companies can't find the information they need to tell them how to prepare a 510(k). Maybe FDA should sponsor a public workshop, live or available free as webcasts, to educate new submitters about requirements and expectations for 510(k) submissions.

Listen to Experts Janice Hogan and Yarmela Pavlovic
Discuss "The Successful 510(k)"

As useful as when it was first recorded, Janice Hogan and Yarmela Pavlovic present the whys and hows of crafting a successful 510(k). Listen on CD or OnDemand and take advantage of their vast experience. Their detailed and thorough presentation covers: 1) the legal framework, 2) finding predicates, 3) choosing the right claim, introducing new features, 4) assessing data requirements, 5) software and combination products, 6) dealing with a not-substantially equivalent (NSE) determination, 7) handling device modifications, and 8) seeing the 510(k) from the reviewers perspective. You'll receive the slide deck, video/audio recording, and links to important guidances. Order here.

CDG disagrees that exemplar devices be retained for current or future reviews. Some devices cost many thousands of dollars, some fill an entire room, and some are not stable. Retaining examples would be unduly burdensome and in some cases an impossibility. Furthermore, one manufacturer should not be compelled to make an example device available to FDA so that FDA can have it available for reviewing a submission from another manufacturer.

Improper use of recognized standards—require a summary of testing
Section 514(c)(1) of the Act describes the possibility of using, as part of a 510(k) submission, consensus standards that have been entirely or partially recognized by FDA. This section states, “[FDA] shall, by publication in the Federal Register, recognize all or part of an appropriate standard established by a nationally or internationally recognized standard development organization for which a person may submit a declaration of conformity in order to meet a premarket submission requirement or other requirement under this Act to which such standard is applicable.”

Working Group Issues
The problems are that: 1) a device may raise questions of safety and performance not addressed by the consensus standard; the standard provides only partial evidence of substantial equivalence, 2) submitters may not use the most current version of a standard, they may not be able to determine which sections of the standards are recognized and which are not (you must turn to the supplemental information sheets), and 3) submitters do not always indicate how they have used the standard or deviated from the standard.

CDG Comments: The recognized version of a standard, not the current version, should be used. The 510(k) Manual should be updated to discuss the proper use of consensus standards and the "Standards Data Report Form for 510(k)s" should be modified to provide a place for summary information and all other relevant information FDA requires.

Where's the rest? The last five recommendations under Finding 4 will come out next week. Got something to add? Please comment below.

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc 

 

CDRH's 510(k) Working Group—Findings 1 & 2



A GLIMPSE OF THE FUTURE?
A Cycle of 510(k) Whitepapers by Nancy J Stark and Kathleen Johnson with
IVD input from Gail Radcliffe

I have to see something visually to really grasp it. It took me nearly a day to reconstruct the timeline presented here and I doubt that it is comprehensive. It's value, I think, is that it emphasizes how events have been happening at CDRH in rapid succession and that respected public groups, such as Consumer's Union, have been complaining for a long time.

In February 2010, CDRH held a two-day "town hall" meeting called Strengthening the Center in which they presented several of their concerns and invited selected industry and user representatives to present theirs. This was followed by two internal surveys—one from the 510(k) Working Group and the second from the Task Force on Utilization of Science in Regulatory Decision Making—published in August 2010.

The 510(k) Working Group's Preliminary Report—What's it to me?
The 510(k) Working Group preliminary report is 120 pages in length. It took me a good four days to make my way through it in detail. My goal in this first cycle of whitepapers is to reduce the report to a manageable chunk of reading, yet to give you a good sense of FDA's probable direction. And, because you are mostly device clinical and regulatory professionals, I intend to speculate on what it may mean in your daily work-life. I've invited my regulatory colleagues, Kathleen Johnson (medical devices) and Gail Radcliffe (in-vitro diagnostics—IVDs), to keep me out of trouble.

The Working Group had seven findings and made a number of recommendations for improvement within those findings, many of them will make our lives easier. But for some firms there will need to be a re-thinking of regulatory procedures if the recommendations are implemented.

Finding 1: There is insufficient clarity with respect to the definition of “substantial equivalence”

The terms "intended use" and "indications for use" are poorly defined
Substantial equivalence begins with determining that a device and its predicate have the same intended use. For IVDs Gail tells me a statement of intended use is required in the electronic submission and is then incoporated into the IVD Decision Summary. It is defined as a description of what the manufacturer intended to measure with a certain test, and typically consists of the following elements: 1) mechanism of assay, 2) what is being assayed, 3) the population being assayed, 4) whether the assay is quantitative or qualitative, 5) whether the assay is an adjunct or a replacement for the gold standard, and 6) what is the next step (surgery, further diagnosis, and the like.)

For non-IVDs, 21 CFR 801.4 defines intended use as the "objective intent of the persons legally responsible for the labeling of the device" and 21 CFR 814.20(b)(3)(i)] defines indications for use as "a general description of the disease or condition...." Kathleen tells me no overt statement of intended use is actually required in a 510(k) submission; instead 21 CFR Part 807.87(e) approaches the subject obliquely saying a 510(k) submission should contain "proposed labels, labeling, and advertisements sufficient to describe ... its intended use...." and 807.92(a)(5) mixes concepts asking for "a statement of the intended use...including a general description of the diseases or conditions...." In practice, the reviewer turns to the labeling and interprets your intention.

The Successful 510(k) Janice Hogan, Esq and Yarmela Pavlovic, Esq Listen to Janice Hogan and Yarmela Pavlovic present the whys and hows of crafting a successful 510(k) on CD or OnDemand. Their detailed and thorough presentation covers: 1) the legal framework, 2) finding predicates, 3) chosing the right claim, introducing new features, 4) assessing data requirements, 5) software and combination products, 6) dealing with a not-substantially equivalent (NSE) determination, 7) handling device modifications, and 8) seeing the 510(k) from the reviewers perspective. You'll receive the slide deck, video/audio recording, and links to important guidances. Order here.

The meaning of indications for use is much cleaner: for IVDs it is a description of why a patient would use a certain test; for non-IVDs it is a disease or condition for which a device will be used [21 CFR 814.20(i)]. A statement listing the indications for use must accompany every 510(k) submission.

If you get a 510k for an intended use and then you add a new intended use, you have to file a new 510(k) and demonstrate, newly, that your device is substantially equivalent to a predicate. But if you get a 510k for an intended use and then add a new indication for use, you do not have to demonstrate substantial equivalence newly. So hypothetically you can keep adding new indications for use to an existing device and never file a new 510(k).

But suppose you add indications like "relieves cancer pain", "relieves pain from third-degree burns", or "relieves pain during childbirth"? These statements meet the definition of a new indication, but they also introduce new questions of safety and effectiveness and FDA will expect to see a new 510(k).

Working Group recommendation
The Working Group recommends combining the concepts of "indications for use" and "intended use" and then calling the combined concepts "intended use". They further recommend only certain characteristics be included under the term “intended use” so that modifications that are currently considered to be only changes in “indications for use” are not in the future construed as changes in “intended use”.

CDG comments: Thirty years of device submissions and regulation are built upon the phrases "intended use" and "indications for use". To reshuffle the definitions now will only cause new confusion but could also create a large backlog of additional 510(k)s that would not normally have to be submitted.

An unambiguous definition of "intended use" and exactly how it differs from "indications for use" is what CDG believes is required. For non-IVDs we recommend the term "intended use" be defined to mean the purpose (such as treatment or diagnosis) or function (such as provide support or stabilize) of the device and that the intended use be clearly set forth in the 510(k) rather than rely on a reviewer's interpretation of the labeling. We would like to see an "intended use" statement form like the "indications for use" form included in the 510(k) required documentation.

Currently, a new 510(k) is not required for the addition of a new indication that does not raise new questions of safety or effectiveness. If the terms are combined, will we end with ten times more 510(k) submissions every year? At the present time, we look for a predicate device that has the same intended use and similar indications for use; if the terms are combined, what will constitute a legitimate predicate?

Amend the Act to provide agency with authority to consider off-label use
It has been known to happen that a manufacturer identifies an easy-to-get-cleared intended use for a device, knowing full-well the device will be used for another purpose or even promoting it for that purpose. But it happens we live in a legal society where, although we may contemplate a crime, we aren't guilty until we commit it.

Working Group recommendations
The Working Group recommends seeking an amendment to the Food, Drug, and Cosmetic Act (Act) so that FDA can consider the possibility of off-label use when reviewing a 510(k) and even force the submitter to change the intended use.

CDG Comment: FDA doesn't regulate medical practice (read the Belmont Report), so if a physician uses a device off-label it is between him, his professional society, and his malpractice insurance. And CDRH already has the authority to clear a device as "substantially equivalent with limitations", meaning the labeling has to contain a statement that there is no data for likely unintended uses.

But giving a reviewer the authority to force an intended use on the submitter confuses the roles of reviewer and submitter and pretends the reviewer is a mind-reader. And as a submitter, you may be forced into a regulatory pathway you don't want, or forced into gathering literature or clinical data you can't afford.

Questions of safety or effectiveness
Here are the reviewer's steps toward clearing a 510(k) submission: 1) determine if the device under review has the same intended use as the predicate device, 2) if so, determine the device has the same technological characteristics as the predicate device, 3) if not, determine if the technological differences raise new questions of safety or effectiveness. If there are none, the device is substantially equivalent (SE) to the predicate and the 510(k) is cleared.

Recommendations
The Working Group recommends the agency develop a core list of technological characteristics that, when different, are likely to raise new new questions of safety or effectiveness.

CDG Comment: The recommended core list will be helpful even in the early stages of device design and development. Some of the technologies identified may be addressable in literature reviews, but others may require animal studies or even human studies. The ability of the manufacturer to predict the downstream consequences of a design change will allow them to plan better and design more wisely.

Finding 2: CDRH's current practice allows for the use of some types of predicates that may not be appropriate

One quarter of 510(k) submissions rely on predicates more than five years old
Predicate age is not, in and of itself, a concern. Using an older predicate may be appropriate for mature technologies. But in many cases device performance has improved dramatically and older predicates are widely recognized as substandard. The Working Group felt that submitters sometimes cited poorly performing predicates, including predicates that had been withdrawn from the market.

In 2009, 29% of the predicates cited were devices not registered and listed in FDA's Establishment Registration & Device Listing database. In most cases the predicate itself was cleared through the 510(k) process and was not required to have an independent showing of safety and effectiveness. Because the agency does not have the technological infrastructure to trace a device backwards to arrive at the "original" predicate for the intended use the reviewer is unable to trace the predicate's pedigree.

Recommendation
The Working Group recommends developing a guidance to describe when a device should no longer be available for use as a predicate because of safety and/or effectiveness concerns.

CDG Comment: We disagree that any legally approved device should be unavailable for use as a predicate, even if the device has been recalled or removed from the marketplace. If a manufacturer makes strides in improving the performance of an older device, they should not automatically be restrained from using the original device as a predicate. FDA has the authority to require evidence of safety and effectiveness if that is necessary.

First, FDA should do its part by improving the 510(k) database with features like term explosion, predicate lists, and text search capabilities. For example, yesterday I entered a single keyword into the classification database and got three hits, all for Class III PMA devices, and then I entered same keyword into the 510(k) database and got 16 records. The classification database is clearly flawed. With better research tools at our disposal, we believe the quality of 510(k) submissions will improve on their own.

Rescission authority
The Act is silent with respect to rescission or modification of device clearance, although the Working Group argues that agencies have inherent authority to reconsider their decisions in certain circumstances such as fraud or error, or to rectify their mistakes.

Recommendation
The Working Group recommends that CDRH issue a regulation to define the scope, grounds, and appropriate procedures for partially or fully rescinding a 510(k) clearance.

CDG comment: Clearly, events of the past few years have shown that CDRH should have the ability to rescind 510(k) clearance. In situations where new information comes to light, or errors have been made, it is reasonable for the agency to revoke a decision. What the industry wants and needs is a level playing field that promotes innovation. What the public wants and needs is an agency that makes impartial decisions to protect the public health.

Multiple predicates, split predicates and bundling
First, let's get some definitions straight. You can argue substantial equivalence using two or more predicates for, say, a multi-parameter monitoring system which combines the functions of several devices. For example, you might combine an ECG and a blood pressure monitor into a single device that performs both functions. Another example of multiple-predicate devices are IVD multiplex assay systems, where two or more analytes are assayed in one well. The "Guidance on the CDRH Premarket Notification Review Program 6/30/86 (K86-3)", also known as the Mohan Memorandum, has allowed this use of "multiple predicates" since 1986.

A "split predicate", on the other hand, is a completely different animal. Here, the intended use of a device is based on one predicate and the technological characteristics are based on another. It's like using a lawn mower to trim a hedge.

"Bundling" is yet a different situation. Bundling refers to grouping many devices into a single submission, with one predicate for each separate device. This is a logical approach to save on user fees for a family of devices. Bundling is described in the guidance "Bundling Multiple Devices or Multiple Indications in a Single Submission" and is accepted by FDA when the devices or indications may be addressed in one review.

The chart on the left shows that the more predicates you use in your submission, the longer the review time. This is logical because the reviewer is compelled to assess the scientific issues associated with each predicate mentioned.

The agency's problem is that it does not have an adequate database to trace the predicates backwards over a number of submissions. They are forced to manually review the text of each 510(k) submission to asses its predicates.

Recommendation
The Working Group recommends the agency develop a guidance describing when multiple predicates are appropriate, disallowing the use of split predicates, and updating its existing bundling guidance to distinguish between multiplex devices and bundled submissions.

CDG Comment: we agree the guidance is necessary and that using multiple predicates makes sense for two or more products combined into one or for multiplex IVD assays; and we agree that bundling predicates makes clear sense for families of similar devices. Furthermore, CDG believes that using split predicates—one for the intended use and one for technological characteristics—is acceptable when accompanied by new data to support safety and effectiveness.

Updated and expanded guidance documents are welcome because they make they make planning regulatory strategies easier and review processes more efficient.

CDG can help write your next 510(k)
Kathleen Johnson is an independent monitor and regulatory consultant for non-IVD medical devices. Gail Radcliffe is an independent regulatory and clinical expert for IVD devices. Both are part of a family of technical professionals who work with CDG, many with 10-15 years experience in their field. CDG has capabilities in in-vivo diagnostic, in-vitro diagnostic, and non-diagnostic medical devices; regulatory engineers; a toxicologist experienced in device biological safety; statisticians; and other professionals who may contribute to 510(k) preparation or clinical trial implementation. We work collaboratively with a point-person on your side so that you are involved in the process every step of the way.

Contact us
Phone or email us at 773-489-5721 or cdginc@clinicaldevice.com.

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc

 

CDRH's 510(k) Working Group Preliminary Report

TAKE THE 510(K) REVIEWER SURVEY
A Cycle of Whitepapers by Nancy J Stark and Kathleen Johnson

It's been a long time coming, with complaints dating back for several years, but FDA's problems really became public when a group of FDA scientists and physicians wrote to John Podesta, head of then President-elect Barack Obama's Transition Team that "America urgently needs change at FDA because FDA is fundamentally broken...the scientific review process for medical devices...has been corrupted and distorted by current FDA managers...." The open letter was particularly significant because it was copied to six senators and four congressman and published in the national press and on every blog on the internet concerned with medical devices.

It was followed by a host of General Accounting Office (GAO) reports, the resignation of Center Director Daniel Schultz and Office of Device Evaluation Director Donna-Bea Tillman, and initiation of an Institute of Medicine (IOM) review of the 510(k) process due out in 2011.

 
Internal Assessment at CDRH
Meanwhile, the Center itself initiated a series of activities to assess the 510(k) process by establishing a 510(k) Working Group and a Task Force on Utilization of Science in Regulatory Decision Making. The Working Group and Task Force published preliminary reports in August 2010.

The working group, comprised of representatives from across CDRH, was assigned to develop an understanding of the way the 510(k) process currently functioned, the perspectives of CDRH staff and a range of external constituencies on the program, and potential areas for improvement.

As part of its research, the Working Group co-hosted a public town hall meeting called "Strengthening CDRH and the 510(k) Process" on 18 February 2010 in conjunction with the Task Force on the Utilization of Science in Regulatory Decision Making. A CD of the public meeting is available at Strengthening the Center.

510(k) Survey
To assess the consistency of CDRH reviewers’ interpretation and understanding of 510(k) regulations, guidance documents, and review practices, the Working Group conducted a survey of the Center’s premarket reviewers and managers. The survey consisted of twenty questions related to reviewers’ and managers’ knowledge and opinions on a range of areas of concern.

Reviewer Cohort. The survey was sent by email to all reviewers in CDRH’s two premarket review offices, the Office of Device Evaluation (ODE) and the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD). All reviewers were strongly encouraged to complete it. Out of a total of 308 reviewers, 215 reviewers took the survey, and at least 162 respondents answered each question.

Manager Cohort. Premarket review managers also completed the survey as a separate cohort of respondents. Out of a total of 38 managers (Branch Chiefs, Deputy Division Directors, and Division Directors) in ODE and OIVD, 21 ODE Branch Chiefs and Deputy Division Directors took the survey, and at least 13 respondents answered each question.

Take the Survey Yourself
We've put the Working Group survey into SurveyMonkey so that you can take the it yourself, benchmark your answers against your colleagues', and then compare your answers to Center staff. It's useful and information to see if your understanding of the 510(k) clearance process is the same as the agency's. Click on survey to take the test, click on benchmark to compare your answers to your colleagues, and then Center Reviewers to see the agency's responses.

When you've finished, submit the form at the end of the survey to receive your OnDemand access to "Surviving Medical Device Recalls" presented by the Center's Bioresearch Monitoring staff.

When you need to write a 510(k), CDG has people who can help
CDG has a family of technical professionals, each with 10-15 years experience in medical devices and eager to help you write your 510(k). We have regulatory professionals for in-vivo diagnostic, in-vitro diagnostic, and non-diagnostic medical devices; regulatory engineers; a toxicologist experienced in device biological safety; statisticians; and other professionals who can contribute to 510(k) preparation. We work collaboratively with a point-person on your side so that you are involved in the process every step of the way. View our company brochure and capabilities sheet.

Contact us
Phone or email us at 773-489-5721 or cdginc@clinicaldevice.com.

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc