October 1, 2019

What role does the CER play in getting a Medical Device Approved for Marketing in the EU?

Author: Suzanne Broussard

Clinical evaluation is an integral part of technical documentation mandated for regulatory compliance of medical devices sold in the European Union (EU); therefore, having a well-designed and clearly written clinical evaluation report (CER) is paramount for manufacturers of both existing and new medical devices. 

This is especially true with the passing of Medical Device Regulation 2017/745 (MDR). The MDR directive places stricter regulations on medical device safety and performance 

Not only are new devices seeking regulatory compliance impacted, devices on the market prior to the initiation of the MDR directive are also affected as every device must be re-submitted for CE marking before the end of the May 2020 transition period. This effect will require manufacturers to update the CER for each device to current MDR standards in order to be in regulatory compliance. 

A survey of medical device manufacturers revealed that 78% of respondents do not sufficiently understand MDR, while 58% do not have a strategy in place to correct gaps in their clinical data or a process for collecting the data needed (KPMG & RAPS). 

With so little time left to meet the MDR May 2020 transition deadline, consider hiring a professional to help your organization prepare the CER document.  

Why is the CER Important for Marketing in the European Union? 

The CER documents a device’s entire clinical evaluation process and is required to achieve regulatory compliance for marketing in the EU. Essentially, the CER outlines the assessment and the clinical data that determine if evidence sufficiently verifies the clinical safety and performance of the medical device. Furthermore, the CER is considered a living document and must be updated on an ongoing basis throughout the devices’ life cycle.  

Key Updates in MDR as Outlined in MEDDEV 2.7/1 Revision 4 

Device Equivalence and Risk/Benefit Profile 

The MEDDEV guidance document 2.7/1 revision 4 outlines the stricter regulatory requirements placed on medical device manufacturers. Several key differences exist between the previous EU Medical Device Directives (MDD) and MDR, including the data requirements to determine device equivalency and clarification on the risk/benefit profile.  

For a detailed gap analysis of the differences in the requirements for device equivalency and risk/benefit profiles between the previous and the current standards see our white paper Gap Analysis Report: MEDDEV 2.7/1 Guidance and Risk/Benefit Profile 

State of the Art is a Central Theme in the Clinical Evaluation  

Establishing and describing the state of the art for each medical device is central to the clinical evaluation because it establishes a reference standard that is used to determine if the device’s safety and performance are compatible with current treatment options. This information is used throughout the clinical evaluation process and is documented in the CER.  

Criterion Edge’s Founder and President Laurie Mitchell outlines steps for developing state of the art to comply with MEDDEV 2.7/1 revision 4 in the white paper “State of the Art: Best Practices and Literature Review Using DistillerSR.”  

Experience Writing CER Documents Matters 

Manufacturers have a lot at stake. Having experienced CER writers that can integrate the complex regulatory requirements with the device’s specific characteristics and can present the information with clarity can save both headaches and money. Pulling together the CER document requires a thorough understanding of the regulations’ meaning and, as importantly, the ability to apply the MDR regulations to each device’s specific situation.  

The role of the clinical evaluator is so pivotal that expected qualifications for the clinical evaluation authors and evaluators are outlined in the MEDDEV 2.7/1 rev 4 guidance document right along with the stricter standards for device equivalency, risk/benefit justification, and scientific validity of data.  

“The clinical evaluation should be conducted by a suitably qualified individual or a team.” 

The list of qualifications to consider when choosing a clinical evaluator to author the CER is clearly stated in section 6.4 of the MEDDEV 2.7/1 rev 4. Foremost on this list are the author’s and evaluator’s qualifications and experience, including an advanced degree, documentation experience, and knowledge of the device being evaluated, research methodology, information management, regulatory requirements, and medical writing.  

All of these requirements can be difficult to find in-house. Poorly organized or incorrect CER documents can hold up the compliance process delaying obtaining a CE mark or result in removal from the market during subsequent inspections.  

Professional CER writers at contract regulatory agencies such as Criterion Edge can help manufacturers on multiple levels: 

  • Provide a gap analysis  
  • Provide a thorough knowledge of the current regulations 
  • Author a complete QC’ed CER document 
  • Review existing submission documents 
  • And so much more…

At Criterion Edge, our clients enjoy our transparency in the services we provide as our candid scoping includes a time frame for delivering the CER and detailed information on gaps in compliance. All of our writers have experience writing CERs and are up to date on current regulations. Providing a comprehensive analysis and subsequent solutions sets us apart from other vendors. Contact us if you would like to have a conversation about what we can do to help with your writing and regulatory needs. 

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September 9, 2019

Managing CER Writing Better with EndNote: Advanced

Author: Ashley Self

Most CER writers work collaboratively with other writers and researchers to complete CERs that often run hundreds of pages and contain roughly five times as many citations. This is where EndNote’s more advanced and collaborative features shine. Within EndNote, medical writers can share libraries and even view/share notations they make on the reference’s corresponding full-text PDF. EndNote also allows writers to group resources and filter out unwanted resources via its robust search functionality.

These 11 EndNote features are sure to increase your efficiency on your next CER project:

Having access to the full text PDF of every resource in your EndNote library is indispensable when working collaboratively. Writers and analysts working over a shared library (covered below) can discuss, highlight and mark-up certain sections of the article when deciding what and how to include the resource’s data points and findings.

EndNote automatically searches for and downloads available PDFs for all citations you import. Note: You can help it by adding your company’s open URL. Open EndNote Preferences > Find Full Text > and input the URL in the OpenURL field. If necessary, add a URL to the Authentication field.

If some resources in your library don’t have the full text PDF attached, you can manually locate those PDFs by selecting the reference or group of references in your list and going to: References > Find Full Text. If EndNote can’t find the PDF of your reference, you can find and download the PDF manually online. Then, in EndNote, select the reference from the list and attach the PDF by clicking the paper clip icon in the lower right window. Or go to: References > File Attachment > Attach File.

If you have a PDF but don’t have the reference for it in your list, you can import the PDF by going to: File > Import > then click Import Options and choose PDF File or Folder > Then select the item you want to import. Using this feature, you can also import an entire folder of PDFs by selecting the Folder and clicking Import. Or, you can designate a folder for EndNote to import from any time you add a file to that folder. Go to: EndNote > Preferences > select PDF Handling from the menu on the left, check the box to Enable automatic importing and select the designated folder. Note: Some older PDFs or scanned PDFs may not contain sufficient metadata.

To markup an imported PDF, click on the reference and open the PDF in its own window. You can then use most standard Acrobat tools to annotate or call out text or sections within the PDF. Note: EndNote can even search your notations.

While most CER writers use a research tool like Distiller SR to locate and screen data studies and resources, EndNote can also be used effectively as a screening tool by way of its Groups categorization and Duplicate Detection tools. In one case, a writer was able to narrow a search resulting in 500 entries (some of them junk) into a small batch of highly relevant resources by filtering out duplicates, outdated data, conference abstracts, non-relevant or excluded keywords, and study types, all in EndNote.

Categorizing existing references from your library into groups makes working with large reference libraries much easier. Particularly when working with CERs when a wide net of data gathering must initially be cast. Many medical writers use EndNote’s Groups feature as a search or screening tool by inputting specific keywords, study types, or journals into the search criteria, and even using specific keywords to exclude unwanted references. Internally, the Groups feature can be used to temporarily flag articles that need further review, need full text, or need additional notations. By assigning a 1- to 5-star star rating to these entries, you can later use the Groups feature to search for those entries by rating and process them accordingly. This is a great way to batch find and process reference groups that don’t necessarily share a common keyword, author or title.

Smart Groups is an automated feature that tells EndNote to automatically add references that meet a specified criteria to a group. Setting up specific Smart Groups in advance is well worth the time as it automates a manual search step. For example: you can tell EndNote to automatically add any new or existing resources that contain the keywords heart valve and the date of 2018 to a 2018 Heart Valve group. To use this feature, go to Groups > Create Smart Group and input the search criteria you desire. Subsequently, any matching reference you add to your library will automatically be added to that group.

Medical writers may also use the Group feature to create new groups from existing groups. Choose Groups > Create from Groups and then input your inclusion/exclusion criteria. For example, say you have created various groups for different types of heart stents and you want to combine some of those groups into a new group. You can select to include the types of stents you want and exclude those you don’t.

Note: The Smart Group feature can even be programmed to search the full text PDF attachment and even your notations within the PDF.

EndNote also has a robust tool for reconciling Duplicate entries. This is a recommended first and final step (when you first import your references into a new library and before you finalize your document) and can be done by going to the References menu > Find Duplicates. This will generate a list of duplicates. From there you can simply delete the outdated references, or click on them to review the data included within each reference, copy and paste desired data into the most recent reference, and only keep the most up-to-date entry.

Library sharing is one of the most attractive advanced features of EndNote and one CER writers use regularly. When multiple users are working on one CER, it is critical that they have viewing and notation access to all the references. The primary creator of the reference library can share the library with up to 100 users (version X8). Anytime any of the users makes a change to the library or notation within in a reference, EndNote keeps track and other users can view the list of changes.

To use this feature, all users must first set up an EndNote Online account. Then, the primary user can sync their library online (this takes a while) and then elect to share the library with a list of users (specified by email address). Recipients will be notified via email and can accept access and then have full privileges within the library. Because the library is constantly changing, the original owner of the library should make periodic backups of the current version via File > Compressed Library.

Similarly, if you are working on multiple devices you can sync your EndNote library across those devices. In order for any changes or updates to transfer to other devices, all devices must be online. Once you have synced your existing library online, open EndNote on the new device and go to: File > New. Here you must create a new library file of the exact same name as the library file on your current device. Then, simply sync that file. (Remember, initial syncing takes some time. Subsequent synced updates happen every 15 minutes and when you close EndNote…and are much quicker.) Now you can work from multiple devices and rest assured your changes will be updated.

When working with new clients, you may receive multiple documents with embedded citations, without receiving access to the related EndNote library. You can still access those references by exporting those citations into a Traveling Library. Go to the EndNote menu > choose Export to EndNote > Export Traveling Library. All the resources cited in the document will be added to your specified EndNote library.

In addition to its most basic features, EndNote can serve as a valuable, time saving tool for CER writers tasked with managing large databases of references. EndNote makes collaborating with multiple writers seamless and efficient, and its group and search capabilities make filtering through added references and managing existing ones much more organized. Note: EndNote is a dynamic and active tool, so don’t forget to unlink the final Word document from EndNote before you send it for review.

 

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August 26, 2019

Managing CER References Better with EndNote: The Basics

Author: Ashley Self

Using a reference manager like EndNote while writing a massive, reference-heavy document like a CER is certainly a game changer for medical writers. EndNote’s core features like Cite While You Write are indispensable when it comes to saving valuable time and keeping thousands of data references organized.

However, EndNote’s more advanced features, like PDF markups, reference library sharing and groups, are particularly valuable to CER writers who typically collaborate with multiple writers, researchers and analysts on one document, and also have to update older inherited CERs they didn’t originally write.

In this article, we’ll cover some of EndNote’s basic features. If you are already familiar with those, you can jump to our next blog on how to make the most of EndNote’s more advanced features when writing your next CER.

Cite While You Write is an EndNote plugin that allows you to add, manage and edit EndNote citations directly from Word while you are working in your document. It is simple to install and you are able to access all of EndNote’s features without leaving Word, which means you can search for, sort, and edit resources seamlessly as you are writing. Just make sure the EndNote library related to the project you are working on is open in EndNote.

EndNote has a database of more than 6,000 citation styles that are updated periodically. Most CERs use the AMA style, however, sometimes writers may be required to use a different style or even make a minor change to an existing style. Occasionally writers may receive a draft document from a client that was cited using a different style.

You can find new or updated styles on EndNote.com. Search for Output Styles and download the ones you want. Then go into your downloads folder, open the new styles in EndNote and save them. You can then access them in EndNote by going to Open Style Manager and searching for the new style.

Perhaps your reviewing body or client wants you to use the AMA style but with a slight variation in the way things are abbreviated. In that case, you can create a custom style based on the existing AMA style. Go to: Edit > Output Styles > Open Style Manager > Find your style and click Edit > Using menu on the left, select the section you would like to edit and choose Templates. Then make any changes to the corresponding template fields. When done, save the file under a new name.

Because CERs and other medical regulatory documents are often hundreds of pages long, it is sometimes preferable to create sub-reference bibliographies for each main document section. To do this for each of your document chapters, you can edit the Bibliography Style you are using.  Go to: Edit > Output Styles > Style Manager > Find your style and click Edit > Using the menu on the left, click on Sections. Here you can choose to have the bibliography at the end of the document or at the end of each section, or both. Save your changes. Then ensure that, within your Word document, each unique section is separated by a “section break”. Note: if your document template or standard formatting contains section breaks for other purposes (such as tables), you will see a bibliography after each section break, so, this style may not work efficiently in those cases.

When working in an already complex CER document, EndNote’s core functionality makes managing large batches of references and citations fluid and virtually error-free. Already, using just these basic features will save medical writers substantial time and mental energy.

When you are ready to dig into EndNote’s more advanced features, you will find it helps with much more than just document citation management.

Stay tuned for the second part of our EndNote series: Managing CER Writing Better with Endnote: Advanced.

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August 12, 2019

9 Tips To Ace The MDSAP The First Time

Author: Suzanne Broussard

Take the advice of industry experts and AOs—the key to acing the MDSAP audit is to prepare, prepare, prepare.

The MDSAP audit process is intense in that it is designed to provide thorough coverage of QMS and multiple jurisdictions regulations. Remember, your organization already maintains a level of compliance in all countries they sell devices. MDSAP simply rolls all these regulatory requirements into an efficient process. Here are a few tips to keep in mind when preparing for the MDSAP audit.

1. Look closely at the MDSAP Audit Model to determine exactly what the Auditing Organization (AO) will need. The MDSAP Audit Model is the AOs guide. Everything needed for the audit is clearly laid out in this comprehensive guide. Each of the 90 questions the AO will ask is contained in this guide. And, each question is cross-referenced to relevant sections of ISO 13485:2016 and other specific requirements of medical device regulatory authorities participating in the MDSAP program.

2. Use the MDSAP Companion Document to create a gap analysis and perform an internal audit. It is universally agreed by AOs and manufacturers that have been through the MDSAP audit process that the best way to get ready for an MDSAP audit is to use the MDSAP Companion Document as a guideline. The Companion Document further clarifies the Audit Model and provides guidance to the auditors, making this a very handy supplement for manufacturers. MDSAP is very structured, and understanding the specific information that auditors will be focusing on and in which order eliminates any guesswork by the manufacturer.

What can I expect during a MDSAP audit?

3. All documents need to be organized and available. The audit is timed. Therefore, the vast volume of documents required need to be organized and quickly accessible—this is critical for a successful audit. The AO will not be able to come back and revisit areas in which documents are not readily available.

4. Organizations must prove control over their suppliers. The way in which you demonstrate control over your suppliers needs to justified, and these details need to be incorporated into procedures and programs. A manufacture cannot simply say their supplier is ISO or MDSAP certified. The AO wants to know how your organization ensures that the supplier is compliant. Here’s why a global medical device manufacturer should consider the MDSAP.

6. Be clear on what is done where. This aspect is especially important for multi-site manufactures. Clearly list the scope of activity at each site and which products are covered by operations. Make sure to define multi-site manufacturing in Stage 1 so the AO can calculate the appropriate time-frame for Stage 2.

7. Employees must be proven competent. Providing objective evidence that employees are competent, not just trained, in regulatory requirements of all pertinent jurisdictions is mandatory.  Objective evidence could include testing after training and job function checks to assure competency is practiced—not just learned.

8. Consider the Auditors Perspective. Brian Ludovico, Executive Director at NSF International, suggest organizations keep in mind the AOs perspectives when preparing for the MDSAP Audit. He provided a number of additional tips in recent interviews: auditors cannot read your mind, please justify your work, and regulatory and quality need to be friends in your organization.

9. Learn From Past Mistakes. Marcelo Trevino, Senior VP of Regulatory Affairs and Quality Systems at Applied Medical, provides insights on how to avoid some of the most common mistakes with European regulatory compliance.  

If you are ready to bypass the hassle of multiple regulatory inspections and undergo a single, rigorous audit which satisfies the quality regulation of each jurisdiction, consider transitioning to MDSAP.

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July 29, 2019

What To Expect During An MDSAP Audit

Author: Suzanne Broussard

Risk Assessment is the Cornerstone of the MDSAP Audit

When preparing for the MDSAP audit, it is important to understand that the audit focuses heavily on risk-based processes, outsourced processes, and validation activities. MDSAP is based on the international quality systems standard ISO 13485:2016, which requires organizations to consider risk from device conception through its lifetime of use. This Risk Management  includes the device manufacturer and the supply chain.

Check out our Resources page for our whitepaper on MedDev 2.7/1 Equivalence and Risk/Benefit Profile.

There are seven “Processes” in the MDSAP audit. FDA’s vision of how all these processes link together is depicted in Figure 2.

The first four “Primary” processes, depicted in the dark blue boxes, and the “Supporting” Purchasing process were all built on a foundation of Risk Management. The other two Supporting processes (note that Device Marketing Authorization and Facility Registration links to two processes), depicted in the light blue boxes, fulfill the requirements of the participating regulatory authorities. There are 90 total tasks.

The MDSAP Audit is designed with the interrelatedness of each process in mind. For example, the manufacturer must identify the linked processes and perform Risk Management in accordance with clause 4.1.2 (c) of ISO 13485:2016. One process naturally links to the next process and the audit is conducted in a logical sequence.

Device manufacturers currently selling in these markets should already be in compliance with each country’s quality regulations, but allocating time and resources for each country’s audit can be challenging. Thankfully, MDSAP’s fruition offers the opportunity to simplify this challenge.  Keep in mind that companies only need to be compliant in markets they are currently selling, and organizations are not allowed to opt out of participating nations in which they sell once they adopt MDSAP (no “cherry-picking”).

Read more about how device manufacturers can benefit from the MDSAP.

Stages of the MDSAP Audit

The audit is very scripted and starts with the Management Process working through each subsequent task straight through to the Purchasing Process. There is no deviation in flow and every “task” is timed. Tasks sections are broken down into Clause and Regulations, Additional Country-specific Requirements, and Links to Other Processes.  

The Initial Certification Audit is conducted in two separate stages, typically several weeks apart.

Stage 1

Stage 1 is designed to determine if the Quality Management System (QMS) and other MDSAP documentation requirements are adequate, evaluate the readiness of the manufacturer, and facilitate the planning of the Stage 2 audit. Stage 1, sometimes referred to as a desk-audit, occurs in real-time, typically via virtual communications between the organization and auditor.

Here is an example of what MDSAP is looking for in Stage 1. “Whenever a MDSAP Audit Task requires an auditor to verify the identification and documentation of a requirement in QMS documentation, this verification should be performed as part of the pre-audit preparation and documentation review, as practical, to minimize on-site audit time and to increase the auditor’s familiarity with the manufacturer’s QMS.“

A deficiency letter is sent out after the Stage 1 audit informing manufacturers of deficiencies. Corrective action can then be taken to avoid getting findings during the physical audit.

Stage 2

The Stage 2 audit activities determine the manufacturer’s actual compliance with ISO 13485:2016 and all the regulatory requirements of the participating jurisdiction in which they market. There are two onsite auditors that split up assignments, typically in individual conference rooms.

The flow and timing of the Stage 2 audit are based on the specific tasks that need to be performed as assessed from the information supplied in Stage 1. The duration is calculated using the MDSAP P0008 algorithm based on the number of tasks and the time allotted for each. Variables like the number of employees and the specific process activities performed by the organization are used in this calculation. MDSAP provides two tools to help determine audit time, both of which are available on the FDA website.


Are you ready to read about our 9 tips to ace the MDSAP the first time?

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Generis American Medical Device Summit 2019

Oct 28-29, in Chicago, IL

Join our President Laurie Mitchell at the AMD summit as she leads a session on day 2: Systematic Literature Review: How to Empower Data-Driven Decision Making.

Interested in discussing regulatory or medical writing projects? Book a free consultation with President Laurie Mitchell and CEO Lalitha Jonnavithula at booth #13, where you can sign up for the chance to win a FREE Amazon Echo!