Category Archives: Government Impacts

MEDICAL DEVICE STANDARDS- Can we shed a little light?

Sometimes identifying the standards that apply to your medical device can seem like looking down a dark tunnel.  Is that a light at the end, or a train coming towards you?  It could be both! 

Long ago and far away, clearance of a US device with FDA did not depend upon conformity to a standard.  FDA, believe it or not, didn’t recognize “voluntary” standards and according to regulation, only FDA could issue a “performance” standard. Some years back, the ice broke and certain standards for evaluation of a device became “recognized”.  One of the earliest was for the evaluation for biocompatibility (ISO 10993 Part 1), which took the place of the old “tripartite agreement”; and now we have a deluge of standards to consider for any new medical device. Soon the trickle became a roar and regulatory bodies began to see the wisdom of recognizing certain “peer reviewed” standards.

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Transfer a 510(k)?

Medical device manufacturers frequently acquire by merger and acquisition a 510(k) from a previous company.  The FDA draft guidance issued December 22, 2014 provides information on how to notify FDA of such transfers.  This is the FDA’s current thinking on this perplexing issue.

The recipient of the 510(k) assumes the responsibility to verify when a 510(k) changes hands that there has been no significant change of the device since the original 510(k) or when the device was most recently cleared by the FDA.  The validity of the 510(k) becomes the responsibility of the purchaser once the sale or acquisition has been made.  Due diligence to determine what changes could have been made which might require an updated 510(k) submission is not the subject of this guidance.

In 2012 the FDA modified regulation 21 CFR part 807 to reflect statutory amendments to the FD & C Act  brought about by the FDA of 2007.  These changes launched the Unified Registration and Listing System (known as FURLS) which allowed FDA registration and listing to be tied to the 510(k) number, for those which require a premarket notification.  This innovation now allows the FDA to track the “K#” with the registration and listing, and thereby follow the sequence of historical transfers of a particular 510(k).

FDA has not yet implemented this cross-functional database feature but in the future the 510(k) database is supposed to link to FURLS, thus permitting the most up to date registration information to be linked to the 510(k) number.  Until this is completed, manual analysis is all that can be accomplished by the general public.

If your company has acquired by acquisition or merger, a premarket notification [510(k)], the notification of FDA that the 510(k) is now owned by your company is as simple as updating the Registration and Listing database.  This information must be updated annually, but may be updated at any time.  There is no additional fee required to update the annual registration for such 510(k) holder update information.  If your company has not previously registered or listed, then there is of course the annual registration and listing fee.  Your company would need to have supporting information concerning the 510(k) transfer in the appropriate 510(k) internal file.  Be aware, if a company had already registered and listed the same 510(k) in the same calendar year, the database might temporarily allow the same 510(k) number to be shown with two companies.  FDA will contact the two companies and seek to resolve the conflict.  Therefore it is important if a 510(k) is transferred by sale, the seller should remove the 510(k) number from their listing to avoid confusion.  Only one company may “hold” a 510(k) at any given time.

For additional information about registration and listing you can go to, contact for help us by way of our website:

Good Laboratory Practice Q&A

FDA frequently issues guidance documents in the form of Questions and Answers.  The August 28, 2013 draft is still lingering on the FDA website pending comments.  But with the FDA’s Refuse to File Checklist, some companies may be in for a shock if preclinical studies are submitted without a statement of compliance to Good Laboratory Practices.  For many years, device studies have been informally allowed to skim GLP regulations but future studies may be in peril if the sponsors don’t appreciate the risks involved in failure to demonstrate GLP compliance.

The Good Laboratory Practice for Nonclinical Laboratory Studies Regulations, 21 CFR part 58 are NOT a suggestion!  According to the GLP preamble, safety studies must follow GLPs, but “functionality studies” are excluded.  This has been the source of confusion since for many device manufacturers, testing an animal-version of a medical device constitutes a “functional” model.  Unfortunately this draft guidance does nothing to clarify this definition. To understand the meaning of this exemption the device test sponsor must understand that the GLP regulations grew out of the pharmaceutical industry where a “safety” study in animals was quite different from one that evaluated the “function” of a drug. When device manufacturers evaluate a medical device for biocompatibility, bone in-growth or potential wear; particularly when histopathology is an outcome measure, FDA typically views these studies as first and foremost: safety.  For all the trouble to develop this guidance, it might have been nice if FDA had made this clear.

If it is too late and your study is complete and you must submit the data to FDA with a submission, it is important to recognize that the FDA will allow a well-written deviation discussion.  It is important to understand that if a study is a pilot trial, failed to include sufficient specimen and there are no “controls”—even literature, then FDA may still reject the data from the study as inadequate for its purpose.  As the saying goes, “you can’t make a silk purse out of a sow’s ear”—pun intended.  If you believe the study was scientifically sound but the laboratory does not employ a Quality Assurance Unit (QAU), there may be ways to demonstrate how well the study was managed and that the data has integrity.  We employ an itemized checklist and demonstrate section by section how the study quality was maintained.  Post-study data auditing can be useful to demonstrate the data should be considered valid, as well as including the laboratory’s AAALAC and/or USDA inspection results with your report.  The most critical issue may be simplest: can you account that all test specimen and all test articles resulted in reported data?  If animal data is missing, if animals died during the study without an autopsy or vet examination of the cause, don’t expect FDA to jump right into believing the data have integrity.  This is risky business and no medical device study sponsor should go into a preclinical study with the idea the study can be conducted as “GLP-like”.  You don’t want to bet your submission, and maybe your company, on the prospect that FDA will accept your position.

Paladin Medical can assist you in developing a scientifically sound preclinical protocol that will result in data that will support your submission.  We can help you to qualify the laboratory and instruct you on methods to augment GLP-compliance deficiencies if certain sub-contractors are not currently compliant.  Despite the FDA’s Question and Answers guidance, it is still more cost and time effective to do the best study the first time with the best laboratory for your device.  Go to for additional information.

Device Master File (MAF)

DEVICE MASTER FILE (MAF) Companies that sell materials, components or manufacturing services should consider the benefits of a DEVICE MASTER FILE (MAF) with the Center for Devices and Radiological Health (CDRH).  A MASTER FILE is a service for your customers but also helps you to maintain control on your company’s proprietary information.  Consider the content of a Device Master File, how it is used by the FDA and your customers, and how it provides a shield around your company’s intellectual property, while providing the quality information your customer needs for their medical device application.  Originally conceived as a means for submitting data in support of a PreMarket Approval Application (PMAA), Master Files also serve to support Investigational Device Applications, 510(k) applications and deNovo submissions. The Device Master File owner controls the content and access to the file by way of a letter to the customer and FDA indicating the scope of access to the proprietary information.

CONTENT:  A Device Master File typically provides proprietary data about a material, a component, or a manufacturing process that the holder of the Master File wishes to make available to FDA on behalf of the customer, without relinquishing control of the contents to the customer.  The proprietary information can take many forms, including proprietary test results and manufacturing processes.  A typical material MAF might include proprietary chemical test results, formulations, biocompatibility and toxicology test results, literature articles and comparative analysis to other materials.  Components, such as batteries, may have reliability and compatibility data, including decay curves, explosive and altitude testing results and storage information.  Contract manufacturers may include process validation protocols and reports, cleaning validation reports and other proprietary manufacturing information.  Process flow charts, raw material suppliers and process risk analysis documents are also included in aDevice Master File.  Consider the content of a Device Master File can be any proprietary information that FDA may need in reviewing your customer’s medical device submission.

ACCESS: Only customers that you designate by letter may have access to your Device Master File at the FDA.  You can indicate in the letter the portions of the Device Master File to which you will allow the access and for the specific device submission; so customers have to request access each time it is referenced.  Some suppliers charge their customers for access to the Device Master File, but this has become less common. The value of the access to the Device Master File is only worth the amount of money that your customer saves by having access to your MAF on file with the US FDA.  If you don’t manage the content to keep it fresh and accurate, there is no value to your customer.  The best Device Master Files are organized with a detailed Table of Contents which allows the customer to know whether or not the contents may be of value to their regulatory efforts.  Typically the holder of the MAF will provide a copy of the Table of Contents at no charge to prospective customers to demonstrate the value of the file contents.  Although unusual, a device manufacturer may choose to file their own MAF in order to facilitate review by different divisions to the same corporate quality information.

HOW FDA USES the CONTENT: FDA will only access your Device Master File when your customer makes a submission to the Agency and includes your access letter.  Only at that time, as the FDA reviews the submission and as the customer designates within the submission, the FDA reviewer will open and review the referenced contents.  This is when the customer will need to be specific as to how the content in the Master File supports their requirements for the submission.  As an example, if the applicant contends that the material’s biocompatibility testing is included in the master file, that section of the MAF would be referenced with a justification for why these data are relevant to the device under review.  If the FDA needs more data, the reviewer states that to the applicant.  If the applicant should request of the MAF holder to add more information and the holder agrees, then the existing File may be supplemented as an amendment to the MAF.  Some Master File holders might decide that the additional testing is the responsibility of the customer, or both parties might strike an agreement to share costs and data access.

PROTECTING DATA in the MAF: Your proprietary information is more secure in the DEVICE MASTER FILE than it is under a confidential disclosure to your customers because the only time the information is accessed by the FDA is when a submission is filed.  However, FDA has made it clear that “under the Freedom of Information Act (FOI), information in 510(k)s, IDEs, PMAs and other device-related submissions, such as MAFs, is subject to public disclosure unless determined by FDA to be trade secret or confidential commercial or financial information within the meaning of 21 CFR 20.61 or otherwise prohibited from public disclosure.”   FDA is required to publish a detailed summary of the safety and effectiveness data forming the basis for the FDA decision to approve, or deny a customer’s PMA (other submission types have different disclosure requirements.)  Therefore it is possible that some information included in the publication would be derived from the contents of the MAF.  To ensure the best protection of proprietary data, MAF holders should identify information in their MAFs which are trade secret or confidential commercial/financial information within the meaning of 21 CFR 20.61. Of course, MAF information already in the public domain is subject to disclosure (e.g., any published literature, catalog, or product specification sheets distributed by the MAF holder to potential customers).

HOW TO SUBMIT A MAF: There is no fee to submit a Device Master File to the FDA, nor any charge to make amendments.  There are however, certain requirements in the file submission so that FDA can log-in the MAF in an expedient manner.  Each MAF is given a file number that must be used on the access letters.  Maintaining the data within the Device Master File as current and of value to your customers should be simple if the MAF is laid out initially with a comprehensive outline.  Not all sections of the MAF need be filed at the same time, as some companies find that filing the portions needed by the first customer helps to expedite the process and “break the ice”.  It is important to realize that FDA does not “approve” the data in the Device Master File in advance when it is filed.  It is only reviewed by particular FDA reviewers when the customer submits the access letter, and only for that particular submission.  There is no limit to the number of MAF that a single company may file.

If you think your company would like to know more about creating and filing a Device Master File, you can find additional information at or contact us at Paladin Medical, Inc.   We can help you get started, work with your staff to compile and file the MAF and help you to decide the content that can best help your customers succeed.  We have outline templates and guides to maintaining a current MAF.                

©Paladin Medical, Inc. 2015

Run the FDA RTA & e-COPY 510(k) Gauntlet

Filing a 510(k) according to the current FDA “refuse to accept” policy can be challenging.  The former checklist of a few pages is now more than 26 pages for a traditional 510(k).  The new policy is supposed to help FDA focus its resources on those submissions which are complete.  Unfortunately some of the quirks of the checklist and the UBER-interpretations of guidance documents and regulations have caught some folks with one or more recycles of their 510(k) submission.  At Paladin Medical, Inc. we have the experience to help you avoid the recycling syndrome by working with you early to plan the content of your 510(k).   Working efficiently and effectively with FDA is much more than checking boxes.  But in like token, we understand that the initial Refuse To Accept review is critical to speedy processing.  For example, we use the checklist to annotate and direct the initial reviewers attention to the location in the document that the required elements can be found.  We know where the trip wires are in the checklist that can stall an otherwise complete submission.   We’d like to share these tips and tricks of the trade with you and discuss your next submission project.  Maybe we can help, or maybe just a look at our presentation given to the LifeScience Alley “Smoldering Submission Issues” can give you the help you need.  Please go to the CONTACT PALADIN MEDICAL tab and sign in for the information request.  We can send a copy of the presentation to your email address.


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