Connecting the Dots: Regulatory & Medical Writing News and Updates

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”).

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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July 15, 2019

Ask the Experts: What does MedDev 2.7/1 rev.4 mean for new and existing products?

Author: Douglas McGarvey

Criterion Edge chats with regulatory authorities and other medical device and pharmaceutical industry experts to share their viewpoints on topics that impact our industry. With this expert advice, we aim to keep you informed about current developments and encourage discussion among those of us who work in large and small medical device, pharmaceutical, or biologic companies, CROs and other industry groups. Our goal is to offer up-to-date and reliable information to help you navigate the regulatory landscape and gain a better understanding of critical issues that affect our industry.

Follow this column/blog to get notified of similar articles. And if you have questions to ask these experts, submit your own questions to us.

NOTE: This forum is not meant to provide legal advice or official policy for any participant. It is simply provided as a discussion between Criterion Edge and various experts for the purpose of sharing the thoughts and opinions of participants.

Ask the Experts: Revision of MedDev 2.7/1 and Clinical Evaluation Reporting

We spoke with an expert from a major European notified body about how companies can prepare for revision 4 of MedDev 2.7/1 and upcoming changes in MDR rules. We discussed how these new regulations affect both new and existing products. Our expert says that the new MDR regulations pose serious implications for clinical evaluation reports based on literature review.

In the future, it will not be acceptable to build a clinical evaluation report (CER) based on literature instruction. This is a significant change! To put this in context, some 80% of products placed on the European market today are based on literature research. Industry experts think that that number will shrink to about 10% following the new MDR requirements.

What does this mean for new products?

For a new product, a literature review will no longer be sufficient to establish equivalency with an existing product. Manufacturers must establish equivalence between the medical device and its equivalent comparator. This requires comparison of devices for clinical application, biological compatibility features and technical parameters. In order to prove that these features are the same for the two products, companies will need to have access to the technical documentation of the equivalent product. It’s not sufficient to simply bring the other product to the laboratory and test it. Manufacturers will need to have two sets of technical documentation. Otherwise, the product equivalency will not be accepted.

For ongoing/annual updates, clinical literature will continue to be important. However, since there is no grandfathering of certificates, every new product will basically get to the European market in the first place based on MDR.

What about an existing product?

Once the MDR changes are in effect, the certification of many existing products will no longer be valid. Even if an organization certifies today, the certification will not be grandfathered into the new system. Every organization will need to go through the new certification process based on the new rules that go into effect in May 2020. It’s important to note the limited timeframe for the new certification process, so companies need to plan ahead.

With regard to current CERs, companies will need to revise and update all clinical reviews. First, they will need to update all of the initial CERs to meet Rev 4 of the guidance document, which is actually very close to the MDR requirements.

Crucially, it will not be acceptable to just focus on safety in order to update the report. It will be necessary to go back and prove the clinical safety of the product in the first place and then to provide updates. This is a major issue for both small and large companies.

Many companies will need to perform clinical studies and, in many cases, retrospective clinical studies. They’ll need robust programs for post-market clinical surveillance (PMCS) and post-market clinical follow-up (PMCF). With the changing rules, manufacturers will need to take a proactive, not a reactive approach, to stay compliant. Companies will need to have a very strong PMCF plan, which is different from requirements in MedDev revision 3.

What sort of reporting is required?

Significantly, companies will need to proactively collect PMCF data. Then, depending on the product classification, they will need to produce two yearly reports with clinical data – a Product Safety Update Report (PSUR) and a Summary of Safety and Clinical Performance (SSCP). The data posted in those reports will come from the company’s post-market follow-up activities.

The Commission is creating guidance documents to clarify what it wants to see in these reports. But this reporting is not the same as a regular CER update. The two efforts must be done in conjunction with each another.

But writing the annual reports is just the beginning – evaluation of the reports is also necessary. Companies must upload the annual reports to Eudamed, the European Databank on Medical Devices, and the manufacturer’s notified body will review those reports each year.

Current discussions among notified bodies suggest that the Eudamed databank will be available by the end of the transition period or the month prior to the implementation in May 2020.

Further guidance

For further guidance, the Notified Body Operations Group (NBOG), a membership organization of European notified bodies, may be publishing papers with their interpretation of the regulations.

‘Ask the Expert’ is published by Criterion Edge, Inc. Criterion Edge, Inc. is a regulatory writing company that provides outsourced writing services to the pharmaceutical and medical device industries. The company’s expertise in regulatory writing best practices, honed over decades, produces superior deliverables and provides budget, resource and timeline flexibility for regulatory managers. We empower companies to deliver superior health care solutions. To learn more about how we do this, click here to contact us.

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