Update on India

The requirements for medical device regulation in India continue to evolve.  The Indian Central Drugs Standard Control Organization have recently published the draft Guidance Document on Common Submission Format for Registration of Medical Devices in India.  This guidance sets out in detail the expectations of the Indian authorities for Device technical file, manufacturing information and certifications that must be submitted in support of Indian licensing application.  The content is based very much on the AHWP CSTD template and the GHTF STED.  The Submission requires specific information on overseas regulatory status - including both product registrations AND postmarket history.  This reflects a trend for emerging jurisdictions to look specifically at the overseas postmarket track record of new products. 

Arthur Brandwood
Arthur@brandwoodbiomedical.com.au

Clinical Evaluation Requirements - Understanding the stricter European Requirements

One of the central components of the last update of the European MDD was to set out far more explicitly the requirements for Clincal Evaluation of devices.  The requirements had, of course, always been there.  Unfortunately they were so generally stated that the observance was not as widespread as it should have been  - particularly for lower risk devices. 

The new directives make the requirements and expectations much clearer.  This led to a lively debate recently on Linked In - in the Clinical Device Group Discussion Forum.  It was apparent from that discussion, mainly amongst US based RA professionals, that there's still some way to go in understanding of the tightened European requirements.

So what are the requirements?

Put Simply: every device must have, within the Technical File, Clinical Evidence to support its compliance with the Annex I Essential Requirements. At this point a simple equation and some definitions are helpful...

Clinical Evidence = Clinical Data + Clinical Evaluation

Clinical Data may, depending on the device nature and risk, be comprised of any mixture of literature, preclinical and engineering data and human clinical trial data.

Clinical Evaluation is the expert report which reviews the Clinical Data and reaches conclusions about compliance with the Essential Requirements based on that review and in particular the clinical performance of the device.

The Clinical Evaluation Report is a key part of the Technical File and needs to be updated from time to time as the device design evolves or more information comes to hand from postmarket experience - e.g. postmarket trials or from customer feedback, adverse events or other information which impact on the conclusions.

One last thing. Interpretations vary around the world (in other GHTF-model jurisdictions) as to who is qualified to sign off a Clinical Evaluation. The European interpretation tends to allow any person who is appropriately qualified by nature of training or experience - which can and is often interpreted to include scientists and engineers who are by training and experience intimately acquainted with and qualified to make sound conclusions from their review of Clincal Data. In Australia the interpretation is more strict - the TGA expects Clinical Evaluations to be signed by an appropriately clinically qualified person - meaning in general a physician but in some cases another clinical professional such as a nurse.

Click here to read the broader discussion on LinkedIn (log in required)

every device must have within the Technical File Clinical Evidence to support its compliance with the Annex I Essential Requirements.

Clinical Evidence = Clinical Data + Clinical Evaluation

Clinical Data may, depending on the device nature and risk, be comprised of any mixture of literature, preclinical and engineering data and human clinical trial data,

Clinical Evaluation is the expert report which reviews the Clinical Data and reaches conclusions about compliance with the Essential Requirements based on that review and in particular the clinical performance of the device.

The Clinical Evaluation Report is a key part of the Technical File and needs to be updated from time to time as the device design evolves or more information comes to hand from postmarket experience - e.g. postmarket trials or from customer feedback, adverse events or other information which impact on the conclusions.

One last thing. Interpretations vary around the world (in other GHTF-model jurisdictions) as to who is qualified to sign off a Clinical Evaluation. The European interpretation tends to allow any person who is appropriately qualified by nature of training or experience - which can and is often interpreted to include scientists and engineers who are by trainaing and experience intimately acquainted with and qualified to make sound conclusions from their review of Clincal Data. In Australia the interpretation is more strict - the TGA expects CLinical Evaluations to be signed by an appropriately CLINICALLY qualified person - meaning in general a physician but in some cases another clinical professional such as a nurse.

Poor compliance of Class 1 medical devices - TGA crackdown coming?

Recent figures reported by TGA showed that random application audits found 40% of Class I ARTG entries were invalid, leading to cancellation of the ARTG approvals.  Although the availability of direct electronic entry to ARTG for Class I devices is not currently under threat, TGA are currently looking for ways to improve compliance.  Expect more refined targeting mechanisms, and mandatory audits for serial offenders. 

Are you preparing a Class I device submission?  Contact us for advice on ensuring your compliance and so you can submit your entry to ARTG with confidence.

FDA takes steps toward 510(k) reform

There has been talk of change to the FDA’s 510(k) pre market notification process for some years now. Increasing pressure from lobby groups, plus the changed climate under the current US administration has strengthened the push for reform.  In February a public meeting was held by the FDA to discuss the issues surrounding the 510(k) process and its effectiveness.  Presentations by FDA representatives highlighted FDA concerns related to the current process.

The 510(k) process involves applicants claiming substantial equivalence of a new low risk device to devices already approved. This can allow applicants to compare and liken their devices to those approved up to thirty years ago, creating cause for concern over the effectiveness and validity of the process.  FDA expressed particular concerns that manufacturers have difficulty selecting appropriate predicate devices and prefer to select the "lowest common denominator" device, or a number of devices as predicates to cover all features of the new device.  FDA are considering methods of simplifying and improving the predicate selection process, with suggested ideas including the publication of more information about approved devices, and the restriction of technically obsolete predicates.

Some higher risk devices and life sustaining or implantable devices are currently permitted to apply for approval through the 510(k) process.  A recent report by the U.S Government Accountability Office (GAO) has raised concern over this and recommended a swift issue of regulations for Class III device types currently allowed to enter the market via the 510(k) process.

In addition, FDA expressed concern about perceived limits to post-market control of 510(k) devices. Post market studies are not a requirement for 510(k) devices in the U.S and FDA has no officially explicit authority to withdraw 510(k) clearances. The non-requirement for 510(k) device manufacturers to notify the FDA of purchase, sale or transfer of 510(k) ownership also presents difficulties for the FDA in tracking post-market activities and adverse events.

The public meeting addressed these issues and more, with the program including a number of presentations by CDRH and speakers from the industry.   For a transcript of the meeting – and video files of the proceedings, click here.

US industry association Advamed responded by asserting that although there’s certainly room for improvement, the 510(k) process is essentially sound.  Advamed recently released a letter of recommendations in response to the FDA’s request for comments following the public meeting, in which many of the proposals and points raised at the meeting are echoed. The news release and letter can be viewed on the Advamed website here. 

Dramatic Slow Down in 510(k) reviews

Amongst all of this discussion of reform, recent experience shows a dramatic blow out in processing times for 510(k) reviews, with applications routinely going over the 90 day review target.  A combination of pressures for more thorough review, increase in applications and FDA’s recent relocation to White Oak have all slowed down reviews.  

Need help with applications to FDA?  In the current climate, strategy is vital. Consider your needs for pre-filing consultations and the possibility of third party assessment alternatives. Brandwood Biomedical has extensive experience of direct interactions with FDA to support 510(k), PMA and IDE reviews.  Contact us  to learn more.

Significant Confusion over Significant Change

In all major jurisdictions, a significant change to a medical device design or to a manufacturing process triggers additional regulatory review. Identification of a significant change and when it’s necessary to notify a regulator can be perplexing at the very least. To complicate things, a change which is considered significant in one product may not be considered significant in another, due to differences in intended use, classification and other factors.

In general terms, a significant change is one which introduces a new design feature, intended purpose or production process and which alters the risk profile. Examples include:

• Any change to manufacturing process, facility or equipment used for the device, affecting the risk of the product. This includes any change to a “special” process which requires revallidation. For example, the addition of a new subcontractor for the “special process” of ethylene oxide sterilisation requires validation of the process and the subcontractor. On the other hand, a new supplier of straightforward components or materials with well defined specifications would not usually be considered a significant change.


• Some changes to manufacturing quality control procedures, including introduction of new methods for testing of quality and sterility of materials and the device.


• A significant design change can include a change in a component material of the product to improve performance which requires new clinical testing to confirm safety and efficacy of the product. A change in design for aesthetic reasons is not considered a significant change.


• Any changes to theintended use of the device, including new or additional uses, removal of uses or changes to shelf life.

Changes to a revised EU Medical Device Directive, which are to take effect in March 2010, include that even one significant change to a product after receipt of CE approval requires that product to undergo the approval process again. The European Notified Bodies association has released guidance for manufacturers, “Reporting of design changes and changes of the Quality System”. In Canada the manufacturer is required to have a procedure in place to identify a significant change and for amending a license in the event of a significant change for Class III or IV devices. Also available are a Canadian Guidance for the Interpretation of Significant Change and an FDA guidance to help with deciding when to submit a 510(k) for a change to an existing device. Still confused? Contact us for advice – we can advise you in determining if changes are significant and assist communications with regulators regarding the change.