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2011: A Year of Change at the FDA? By Robert J. Kerwin, Esq.

Monday, January 31, 2011

Stronger Oversight of Medical Devices:
FDA Preliminary Reports and Recommendations on the 510(k) Process

A version of this article appears on the Business Leader Post.

Each year the U.S. Food and Drug Administration ("FDA") receives over four thousand applications are submitted for approval of medical devices.  For thirty years, under the U.S. Food and Drug Cosmetic Act ("F.D.C.A."), medical device manufacturers have been required to demonstrate to the FDA that new medical devices are safe and effective.  The Medical Device Amendments of 1976 established a regulatory framework for regulation of medical devices.  Devices that pose the most significant risk and scientific uncertainty must go through the most comprehensive testing.  At the risk of oversimplification through the 510(k) process, it should be said that devices are permitted onto the market if they are "substantially equivalent" to devices already marketed.  New devices are classified by comparing them to devices in commercial distribution to determine if those devices are substantially equivalent.  Hence, the statutory scheme for approval builds on existing approved devices.  One knowledgeable trade association observer has commented that "all legislation subsequent to the Medical Device Amendments of 1976 is built into the original statutory foundation".1 The FDA has been charged with carrying out its safety oversight responsibilities in a way which fosters innovation so that devices are neither over regulated nor under regulated.   However, concerns have been raised, both internally and externally, as to whether the FDA has been reaching its goals.  Consumer groups have complained in the wake of firestorm over approval of the ReGen Biologies knee device that political influence should have no place in the FDA review process.  Other industry stake holders have suggested that FDA reviewers "post ReGen" have become overly restrictive in their reviews and that the process has become "frozen".  Mark Leahey, the respected President of the Medical Device Manufacturers Association commented: "some companies are even forgoing the U.S. market and launching outside the U.S. with no intention of commercializing here until the environment improves".  Editorial, "FDA Reviews the 510(k) Process; An overview a dated June 2010" Orthoknow.  In response to the increased criticism of the medical device review process, the Director of the FDA's Center for Devices and Radiological Health ("CDRH"), Dr. Jeffrey Shuren, established internal working groups to examine the Section 510(k) process.  (Note: the CDRH is the center within the FDA responsible to ensure that medical devices are safe and effective.)  CDRH's activities include regulatory review of product evaluation, manufacturing and distribution. 

Preliminary Reports Released

On August 3, 2010 the FDA released for public comment two long awaited reports from the internal FDA working groups on improving the FDA's medical device pre-market review process.  The FDA released a 119 page report from the FDA's Center for Devices and Radiological Health ("CDRH") entitled "510(k) Working Group Preliminary Report and Recommendations".  The FDA also released a 51 page report from the CDRH entitled "Task Force on the Utilization of Science in Regulatory Decision Making Preliminary Report and Recommendations". 2  See CDRH Preliminary Internal Evaluations.  Both reports contain summaries of the Findings and Recommendations in outline formats which are just a few pages long.  The internal reports were, in many respects, unusually frank and self-critical of the FDA's 501(k) process and seem to recommend increased evidentiary bases.   

The current framework for the 510(k) process is a composition of legislative, regulatory and administrative guidance.  However, the statutory language of Section 510(k) does not contain any specific requirements as to how the FDA should review pre-market notifications.  This has drawn criticism.  The 510(k) Working Group Report acknowledged this in its Report in this regard:   

"Some have asserted the [510(k)] program needs to be fundamentally re-thought – that a determination of substantial equivalence to a predicate is insufficient to provide reasonable assurance that marketed devices are safe and effective (emphasis supplied)". Report at 16.

The FDA Report also acknowledged the alternative view of some critics that the statutory and administrative framework is sound, but the transparency and consistency of the program's administration needs to be improved.

The "510(k) Working Group" recommendations, if adopted, will require Section 510 (k) submissions to contain greater evidentiary detail with regard to demonstrating reasonable assurances of the safety and effectiveness.  The "Utilization of Science Task Force" recommendations call for 'more complete' information about the risks and benefits of a device.  Though disagreement exists as to what will be the final outcome of the review, there seems to be unanimity that significant changes are underway at FDA.  Though it is not possible to address fully the lengthy Reports, this article seeks to provide an overview of the Reports' recommendations. 

The Working Groups' recommendations are sure to be greeted by some in the medical device industry with concern that the process will become longer and more complicated.  In an August 9, 2010 article in The Gray Sheet Dr. Shuren acknowledged that comments on the Recommendations were generally positive.  Director Shuren also noted: "by the same token, many of the comments have been tempered-some from the industry expressing concerns about some of the recommendations, although recognizing the devil is the details and some on the consumer side saying we should go further than we have already." 3  Indeed, on January 19, 2011, the FDA announced a Plan of Implementation by which twenty-five steps will be taken to implement a so called smarter and more effective 510(k) Program. See Plan of Action for Implementation of 510(k) and Science Recommendations (PDF - 130KB)  

While an additional report from the Institute of Medicine is expected to be released in the Summer 2011, and while the FDA has stated in its report that it has not made any decision on specific changes to pursue, industry observers expect that the core of the Reports' Findings and Recommendations will eventually be adopted in the form of new regulations and guidance documents.4 

510(k) Working Group Evaluation of the 510(k) program

The 510(f) Working Group was actually comprised of ten subgroups from CDRH.  These included: (1) Bundling; (2) Device Modification; (3) De Novo; (4) Indications for Use; (5) Level of Evidence; (6) Predicates; (7) Standards; (8) Technological Characteristics; (9) Third-Party Review; and (10) Total Product life cycle.  Each subgroup was made up of CDRH staff at various organizational levels.  CDRH also assembled a separate team to analyze quantitative data.  Public participation came in the form of public meetings including a public meeting on February 18, 2010, and on June 22, 2010.  The Report also includes public comments logged from January 27, 2010, through March 19, 2010.  A new public meeting on some of the agenda items is scheduled to occur on April 7-8, 2011, at the FDA headquarters.


Pre-market approvals of medical devices must occur under the Medical Device Amendments to the F.D.C.A.  The Section 510(k) process is one of two FDA pre-market review procedures for pre-market approval.  This pre-market notification procedure is often referred to as the 510(k) process by its statutory reference.  Note: The PMA process is analogous to the New Drug Application process in that sponsors must submit valid scientific evidences, often based on clinical trials to establish safety.  The "submitter must demonstrate reasonable assurance of the safety and effectiveness of the new device for its intended use", 510(k) Report at 22.   However, medical devices may be marketed without independent pre-market approval if the FDA concludes through a review of a "Section 510(k)" submission that a device meets the "comparative standard of "substantial equivalence" to a predicate medical device".  "Substantial equivalence" is determined by regulation by a comparison to a medical device that was lawfully marketed prior to 1976, or to a device that has been cleared through the 510(k) process. 

Key Findings and Recommendations

Substantial Equivalence Clarification.  The FDA acknowledged in its 510(k) Report that although the standard for device clearance under the section 510(k) process is "substantial equivalence" to a "predicate device", it is challenging for the FDA to apply consistently and appropriately the standard without a clear, coherent and reasonable explanation of key terms in the statutory definition of "substantial equivalence".  510(k) Report at 41.  Some critics had contended that the FDA reviewers alter their objections with each new submission to create a moving target of objections that cannot be satisfied.  Others suggest that a supervisory review of a not substantial equivalent decision (effectively, an administrative appeal) is not working.  The 510(k) Working Group recommended that the CDRH clarify the meaning of "substantial equivalence" through guidance and training.  The Working Group noted in particular that there is "insufficient clarity" about what constitutes the "same use" as the predicate device versus a new "intended use" and clarity issues when "different technological characteristics raise different questions of safety and effectiveness".5  Of particular significance, the Working Group acknowledged exercising past ‘flexibility' in construing the "intended use", the lack of clarity regarding "intended use" and "indications for use", both inside and outside CDRH.  The Working Group also acknowledged that submitters should be permitted, as appropriate, to change labeling on devices without such necessarily constituting a "new" "intended use".  510(k) Report at 45.  The Working Group recommended that existing Guidance's be revised and consolidated

Among the recommendations made in the reports are: the establishment of a new class of device (subset of class II) for which clinical and/or manufacturing information would typically be necessary to support a substantial equivalence determination; the disallowing of certain predicates; changes to the concept of "intended use" of a device; streamlining the de novo 510(k) approval process and improvements to the 510(k) data base and notice to the industry.

Where Do We Go From Here?

Though the FDA emphasizes that no formal decisions or timetables have been made and that the FDA is soliciting public input on these recommendations, past history advises that stakeholders ought to plan as if the key recommendations are likely to be adopted.  The FDA will of course access public comment and consider the Institute of Medicine's  ("IOM") independent study of Section 510 (k) scheduled to be released in the Summer, 2011.   Some have suggested that the FDA has left many tough decisions to the IOM. It seems prudent however given the breadth of FDA's input (from ten internal subgroups and a variety of internal and external sources) that submitters take seriously the recommendations contained in the Reports.  Of greatest portent, seems to be the findings and recommendations pertaining to "Substantial Equivalence".  The 510(k) Working Group recommended that those offering 510 (k) submissions provide greater assurance that any comparison of new devices to a predicate device should be valid and well reasoned. Guidance documents are certain to follow in this regard as well as for predicates that are no longer appropriate as comparisons.  The gravamen (if there is one) of the Reports seems to be that there is insufficient clarity with respect to when a device may be marketed without pre-market approval because of a determination that the device is "substantially equivalent" to predicate devices that are already on the market.

It is not clear that those industry stakeholders who claim that they are "frozen" and cannot encourage funding for new initiatives are going to be pleased by the preliminary reports.  Likewise, the consumer advocates may find the preliminary reports a bit uncertain as to the exact changes to be finally adopted.  However, the FDA points to its recent involvement with infusion pump recalls and its intention to draft further guidance in this area as exemplifying FDA concerns for tighter oversight.  How all of this turns out for the roughly four thousand submissions made each year remains a bit of a mystery.  It will also be interesting also to consider how all of this fits in with the recently signed information-sharing Memorandum of Understanding with the Centers for Medicare and Medicaid Devices. See "Memorandum of Understanding between the United States Food and Drug Administration and Centers for Medicare & Medicaid Services".  Future articles will also address possible linkages. We are hoping that this comprehensive analysis will enhance regulatory predictability.

Use of Predicates

The 510(k) Working Group found that CDRH has a current practice which allows for the use of some types of predicates that may not be appropriate.  See Section, Finding, 5.1.2 Report at page 55.  The Working Group further highlighted concerns that at least twenty five percent of the submitters were citing devices that were cleared at least five years before the time of submission and that eight percent of the most recent submissions cited predicates that were submitted over ten years ago.  In addition to the predicate age, the 510(k) Working Group identified that submitters sometimes cite "poorly performing predicates" and even cite devices that have been withdrawn from the market.  Report at 56.  The Working Group recommended that the CDRH consider developing a guidance document as to when a device should no longer be available as a predicate.  The Group recommended that the CDRH consider issuance of a regulation to define the scope grounds and appropriate procedures to fully or partially rescind a Section 510(k) clearance.  The Working Group also found the use of so-called split predicates was a concern.  Report at 58.  "The term "split predicates" refers to a situation in which a 510(k) submitter is attempting to split the 510(k) decision-making process by demonstrating the new device has the same "intended use" as one predicate and "the same technological characteristics as another predicate". Though there are clearly differences of opinion in the FDA on split predicates and their relative helpfulness, the FDA acknowledges these differences have led to inconsistent treatment of 510(k) submissions.  Additionally, there seems to be confusion as to the use of so-called "split"or "multiple predicates".  The Working Group recommended that the CDRH develop a guidance document on the appropriate use of more that one predicate and the misuse of multiple predicates.  Report at 62. 

De Novo Classification Process

For devices for which there are no predicate, but whose risks may not warrant a PMA approach, the "de novo classification process" was established.  The CDRH guidance provided in applicable part that "in order to be places in Class I or Class II under the evaluation of 'Automatic Class III' Designation provision a device must first have been reviewed in connection with a 510(k) pre-market notification"  Report at 64.  The longer 510(k) working Group examined the longer time frames for 'de novo classification' and noted understandably that one limiting factor is that CDRH conducts a full 510(k) review prior to initiating the 'de novo' process.  Accordingly, the 510(k) Working Group recommended that CDRH revise the existing guidance to streamline the current implementation of the de novo classification process and clarify its evidentiary expectations for de novo requests. Report at 66.  The Group encouraged pre-submission engagement between submitters and review staff.   

Disclosure to FDA of all Updates

Under current FDA regulations and guidance, a manufacturer is not required to submit a new 510(k) for a device modification unless the modification "could significantly alter the safety or effectiveness of the device".  21 CFR 807.81(a)(3).  As a result, the CDRH does not always have complete information about the current functions and features of devices.  Although submitters are encouraged to submit a list of modifications, there is no requirement to do so.  According to the Report, a new 510(k) is required for even changes which may have a positive effect.  In order to address ‘unreported device modifications' which may be occurring without adequate level of regulatory oversight, the Working Group has recommended that CDRH revise existing guidance to "clarify what types of modifications warrant a new 510(k) and for those modifications that do warrant a new 510(k), what modifications are eligible for a Special 510(k).  Report at 69, In this connection, the Working Group recommended that CDRH explore the feasibility of requiring each manufacturer to provide regular, periodic updates to the Center listing any modifications made to a device without the submission of a new 510(k) and explaining why the modification did not require a 510(k). 

"Further Definitions as to Submissions"

A 510(k) submission must, among other things, contain pursuant to 21 C.F.R. 807.87 and various FDA guidance documents6:

  1. Proposed labels, labeling and advertisements sufficient to describe the device; intended use and the direction for its intended use;
  2. Photographs or Engineering Drawings
  3. A statement indicating the device is similar to and/or different from other products (and supporting data);
  4. Performance Specifications and Device Design Requirements;
  5. List of all patient contacting components and their respective material

Notwithstanding the FDA's guidance, the 510(k) Working Group noted that the quality and clarity of the 510(k)s vary.  They note that the information is often summarized and inadequate in its level of detail.  The Working Group have recommended that CDRH consider adopting and "assurance case" framework for 510(k) submissions by which submitters formally demonstrate the validity of a claim.  The CDRH would develop a guidance to reiterate "longstanding expectations" that submissions should describe any modifications made to a device since its previous clearance.  CDRH would provide training for FDA reviewers and managers on how to evaluate assurance cases.  Report at 71.  The Working Group has recommended that detailed photographs and schematics be provided which might be added to the public database to the extent not containing proprietary information.  At least one unit of the devise would be available for FDA review.  CDRH would also provide additional guidance and training for submitters and review staff regarding the appropriate use or recognized consensus standards on the evaluation of device safety and effectiveness.  Report at 72.  To address the possibility of incomplete information, the Working Group has recommended revising 21 C.F.R. 807.87 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 know or that should be reasonably known to the submitter."  Report at 74.

Type and Level of Evidence

Though many 510(k) submissions include some bench and animal data, the Working Group has recognized a key review challenge to be determining when other types of information may be necessary to support a substantial equivalence determination.  The Working Group candidly acknowledged that the CDRH may lack familiarity with particular device types of technology.  Given that certain device submissions are commonly associated with data needs, the Working Group has suggested that a guidance "defining a subset of Class II devices, called "class IIb" devices for which clinical information, manufacturing information, or potentially, additional evaluation in the post-market setting, would typically be necessary to support a substantial equivalence determination" Report at 76. 


Industry observers are guardedly optimistic that the January 19, 2011 Plan of Action, if implemented successfully, will clarify and streamline the regulation development process.  As Director Sherun noted:  "the new actions we are announcing will strengthen our most commonly used pathway to market  for medical devices, called the 501(k) Program."  Lets hope that the innovation and safety goals are realized.

Robert J. Kerwin, Esq.  has served as general counsel to the International Association of Medical Equipment Remarketers and Services, Inc.  for seventeen years, and is a shareholder in the Boston firm of Tarlow, Breed, Hart & Rodgers, P.C.  Comments concerning the article may be sent to or to speak with Rob (617) 218-2039.


1 "The 510(k) process: The Key to Effective Device Regulation", Advanced Medical Technology Association (AdvaMed") White Paper at page 8.

2 The full titles are respectively identified as "CDRH Preliminary Internal Evaluations – Volume I-510(k) Working Group Report and Recommendations; and "CDRH Preliminary Internal Evaluations - Volume II Task Force on the Utilization of Science in Regulatory Decision Making Preliminary Reported Recommendations.

3 On December 8, 2010 thirteen US Senators issued letter to the FDA calling on the FDA to streamline the process and urging it to reform.

4 The last extensive FDA guidance document in this area was released in 1998.

5 See 21 C.F.R. 801.4 and 21 C.F.R. 814.20(b)(3)(i).

6 Guidance for Industry and FDA staff: Format for Traditional and Abbreviated 510(k)s (August 12, 2005)