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.

Do you like it?0
July 9, 2019

Criterion Edge at the MedTech Summit 2019, Brussels

Examining MDR Implications on Data Management
Download this presentation

Some of our team members attended the MedTech Summit in Brussels a few weeks ago. Our President Laurie Mitchell presented on a panel with Bassil Akra from TÜV SÜD, Peter O’Blenis from Evidence Partners, and Caroline Byrd from Leica Biosystems. The topic: ‘Examining the Implications of the MDR on Data Management: Collection, Triage, Management and Reuse of Data for Regulatory Purposes.’

Do you like it?0
June 17, 2019

Now you can have a robust clinical study protocol

Author: Aarti Urs

Once your team receives the long-awaited approval to conduct a clinical study on your favorite compound or device, it is time to turn the wheels full speed. But before you begin with your study, you will need to write a detailed clinical study protocol (CSP). A CSP is the single most vital document outlining these questions: Why is the trial being conducted? How should it be executed? And what are the contingency plans? It is a crucial communication document between the investigators conducting the study, IRB, and federal regulatory agencies. According to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) E3 , CSP is a document that describes the objective(s), design, methodology, statistical considerations, and organization of the trial. In order to write a solid, error proof protocol here are a few tips:

1. Always begin with a template

While writing the CSP it is crucial to keep the “audience” in mind. You will be communicating with physicians, nurses, IRB members, and scientific reviewers. Before you begin writing, read ICH E3 guidelines for the topics which are necessary to include in a fully integrated protocol. Consolidate the list of documents provided in ICH appendix 1 needed for your protocol so that you do not accidentally omit any item. These guidelines are meant to be as a guidance document which can be modified or adapted to better communicate the information if necessary.

To avoid any ambiguity and present a complete, well organized and easy to read report, many NIH programs encourage or require the use of protocol templates. There are many different templates available on the internet. Most of these templates include a detailed list of items that should be incorporated into the protocol.

2. Include right amount of details

The rule of thumb is to include the right amount of details to effectively communicate the study requirements to the reader of each section.

Thus, the protocol must inform the study staff about how the study treatments will be assigned, how the subjects are to be treated, and what assessments are to be performed when, with what equipment, and by whom.

It should inform pharmacy staff about how the study medication will be packed and when to dispense, return and track. It will also specify whether special storage facilities are required. There should be enough detail for the lab staff on how to obtain biological samples together with the allocation of responsibilities for their analysis.

Even at the protocol writing stage, there should be a clear idea of the data to be collected and the analysis to be performed.

ICH E3 Guideline provides guidance on the amount of detail expected from the data reporting: “The report with its appendices should also provide enough individual patient data, including the demographic and baseline data, and details of analytical methods, to allow replication of the critical analyses when authorities wish to do so. It is also particularly important that all analyses, tables, and figures carry, in text or as part of the table, clear identification of the set of patients from which they were generated.”

The guidelines also including the detailed discussion of adverse events: “The full integrated report of the individual study should include the most detailed discussion of individual adverse events or laboratory abnormalities, but these should usually be reexamined as part of an overall safety analysis of all available data in any application.”

3. Create a concept-protocol by mapping out the schedule

An excellent way to simplify protocol writing is to create a concept-protocol by laying out the study schedule. This concept-protocol is an initial map showing the visit timings, study phases (e.g. screening, run-in, dose titration, wash-out, treatment, follow-on etc), inclusion/exclusion criteria and assessments, including relevant notes on how specific assessments are to be performed and what time points should be used for analysis. Mapping out the study timeline upfront reduces the likelihood of any changes during protocol writing, which in turn streamlines the production of the protocol. This is not a regulatory document so there is no standard format. It can be in a tabular form, a flow diagram or just bullet points. This is a condensed version of a protocol which can outline the “big picture” in a small, succinct format.

4. Keep your background to the point and provide solid rationale for your study

All protocols require a section detailing the scientific rationale for a protocol, and the justification in medical and scientific literature for the hypothesis being proposed.

The Introductory section should be as succinct as possible and should be organized in a logical, sequential manner. Background and rationale should not be more than 3-5 pages and can be referenced back to the investigator’s brochure, full grant or key literature references, if necessary.

5. Have a clear primary objective

Instead of trying to answer too many questions at the same time, it is necessary to get one primary objective right. However tempting it maybe to try to answer multiple questions at the same time, it will unnecessarily complicate the study  by adding potentially confounding variables that may impede the interpretation of data. The objective should be (SMART objective): Specific, Measurable, Achievable, Relevant and Time based.The primary objective must be well-defined with a well-founded rationale that is logically explained in the introduction of the protocol. This will also help to convince ethics committees that the question needs to be answered, and that it is being addressed by the trial in an ethical way with the best interest and safety of subjects in mind.

6. Be clear about your endpoints

The primary objective of the CSR dictates the primary endpoint. Primary endpoint is sometimes called primary outcome measure or primary variable.  Primary endpoint also requires clarity of thought in order to justify the choice of endpoint, which needs to align with the expectations in your field. Try to keep your endpoints quantitative/ objective (e.g. Blood pressure, laboratory values etc), as opposed to qualitative/ subjective (Pain, discomfort etc). In case of subjective endpoints, try to back up these measurements with surrogate markers (e.g. laboratory value) that correlates with disease or symptoms. Alternatively, a validated scoring system can be considered.

Primary endpoints will also determine sample size. If the subject numbers run to be too large and impractical with respect to funds, it is important to consult statisticians.

7. Consider multiple perspectives (FDA vs IRB)

Since the protocol has to be approved by both IRB and FDA, it is important to consider their complementary but distinct perspectives. IRB protects participants of the study by ensuring that risks to the participants is minimal and reasonable in relation to the anticipated benefits of the study. IRB also ensures that no specific gender, race, ethnicity or socioeconomic status of participants is disproportionately bearing burden or reaping benefits of the study.

FDA on the other hand, focuses on how the safety and efficacy of the drug or device affects the overall population. Hence the study results must provide rigorous evidence that the drug or device is for the welfare of people. Most investigators are well aware of FDA requirements but are less familiar with IRB requirements. Less invasive study designs and optimal use of all data points is the key to protect subjects and achieve IRB approval. Robust study design with validated safety and efficacy endpoints is the key for FDA approval. If a study protocol requires more than minimal risks, include a compelling rationale for the need of these procedures.

8. Recognize your weaknesses and invest in gaining technical expertise if necessary

It is crucial to critically analyze yours’ and your organization’s strengths and weaknesses that would reflect in the protocol. Once you identify any weaknesses, fill those gaps by seeking outside expertise or by investing in training internal staff. Early investments to strengthen your study design will reap long term benefits.

9. Get your protocol reviewed independently by experienced peers

Do not hesitate to take outside help on reviewing your protocol. Ask an outside member of the scientific community or a colleague to review your protocol. This will provide you invaluable feedback on the clarity of your writing, and whether your protocol has enough details for an outside member to understand your study and rationale behind the study.

10. Get professional writing help if needed

If you lack the necessary writing expertise to generate a robust CSP, it would be prudent to seek professional writing help.

We are a team of full service medical writers with expertise in regulatory know-how and focus on flawless execution, thereby maximizing your chances of success. Contact Criterion Edge to learn more about our writing services and follow us on Twitter and LinkedIn.

As Antoine de Saint said “A goal without a plan is just a wish.”  Writing down a robust plan, investing in proper resources and seeking outside expertise to bridge any internal gaps in knowledge is the key to successful execution of clinical study. Good luck with your CSP!

Do you like it?0
June 4, 2019

Resume Tips from a Medical Writer Hiring Manager

Author: Ashley Self

I’m staring at a large pile of medical writing resumes on my desk. Is yours in it? Can I tell from one glance whether you are a good candidate for the position? Will the format and content of your resume make me want to read the entire thing?

If you dread updating your medical writing resume or CV, you are not alone. Of all the critical documents you produce, this is one that requires the perfect balance of accuracy, brevity and noteworthiness. There are a lot of ideas and tactics for making your resume shine, and that can make it easy to go overboard. What I am looking for is a true representation of your experience and skills. I can discern between facts and embellishments, and I prefer facts, even if that means your resume is a little shorter than other examples you may be trying to follow. Your transparency also helps me place you in a position where you will thrive, ensuring what will hopefully be a long-term relationship. (Note: honesty and transparency are equally valued during the interview phase.)

Crafting a resume that stands out can be difficult, but it is well worth the effort. And you can start by doing the following:

Nailing the First Impression

Let’s be honest. I skim through the resume pile. Therefore, it’s very important that you highlight relevant information and format your document to make that information easy to find. The order in which you list your experience and expertise will vary depending on your background (read Resume 101 below). What’s more important is how you present it.

Resume 101

Basics   Every resume should include the basics: summary, professional experience, education, skills, specializations, certifications, and published works. If you are just starting off in your career and have more education than experience, it’s OK to highlight your skills and education first. To flesh out a resume early in your career, list specific coursework and projects you worked on during your education.

Keywords   If you are applying for a job described as: medical writer with experience with CER writing, FDA regulatory approval guidelines and MDR guidances in the medical device field, the key parts of your resume should feature those keywords. The keywords should appear naturally within your summary and professional experience, rather than seem

Customizing   Ideally, you will customize your resume for each job you apply to. This will allow you to tweak your summary, keywords and bold/highlighted type to appeal to the specifics of the particular position.

Continuity   The experience and expertise listed in your resume should match whatever you have listed online on your personal website, LinkedIn profile and other professional profiles.

Format   Use only the most basic formatting tools on your resume. That will ensure that it can be read properly by automated scanning software (if the company you are applying to uses it). If file format is not specified, it’s best to submit your resume as a PDF, as a PDF is static and can be read by almost anyone without shifts in formatting. Within the body of your resume, you can use varying font sizes, all caps, and bold to call out each section, and even horizontal and vertical lines and indents to help organize the information. The rest—such as color blocks, graphics and playful fonts—is best left for more creative presentations. Consistency in style and simplicity in design are key. The proper use of formatting is also a chance to show off these valuable skills to your employer.

Applications   While it sounds a little old fashioned, most hiring managers in the medical regulatory field want to know that you have experience working with complicated Microsoft Word and Excel templates and formatting.

Proofread   If you aren’t an amazing proofreader, ask someone else to look over your resume before you submit it. One trick I like to do is copy and paste the text into a new document and then change and/or enlarge the font and re-read the text. That can help you locate small mistakes you may have missed.

A Quick Note About Recruiters   Any recruiter inquiry should be treated with the respect and professionalism you would give your potential supervisor. Often recruiters aren’t as familiar with the details of the position or as knowledgeable about the field of work as the employer would be. This can be misleading to candidates who incorrectly assume the position isn’t worth pursuing. Dismissing a recruiter’s request could cost you a great opportunity.

Your resume layout doesn’t have to be fancy. It should be simple and easy to read, with a clear delineation between sections. Don’t be afraid to use bold type, bullet points and sub-headings to highlight work experience and expertise that is directly related to the job you are applying for. This will draw my eye and make scanning much more efficient. Just be wise about what you highlight; a few words within each block will suffice.

A brief but rich summary statement at the beginning of the resume is also a great place to let me know exactly what I might find interesting within your resume body. Here, again, if your experience is extensive, you can follow the summary with a bulleted list of relevant specifics.

For example:

Summary: I have over 20 years of experience bringing large and small medical device manufacturers into regulatory compliance in five countries. I’ve supervised clinical trials and managed data collection, quality control and labeling to help several manufacturers meet global regulatory guidelines.

  • X subject matter expert • CE marking and UDI compliance experience
  • Project and team management • RIMS design and implementation

Finally, if your work experience is comprehensive, you can provide a short summary of career highlights to call out specific accomplishments as an introduction to your professional experience section.

The keyword here is “specific.” These sections must be succinct, and should include details, not generalizations.

Demonstrate Your Own State of the Art

Now that you have caught my eye, use the professional experience and education sections to back up your claims. Match the text you have called out in your summary section within each job description and highlight accomplishments in addition to outlining your duties. Be specific: instead of “responsible for regulatory compliance for all products” try “brought 25 legacy and 12 new products into compliance with new MDR guidelines.”

If you have many years of experience, your resume may be quite long. In that case, feel free to provide a separate document highlighting your relevant experience and accomplishments relating to a specific skill (e.g., a list of all the CERs you have prepared, details on regulatory statements you managed for a specific device category, etc.)

Similarly, a separate page with links to published work or accolades is better than listing those within the body of the resume where they may get lost.

If your resume is short, it’s OK to highlight your specific skills. Accuracy, the ability to work with a team, the ability to meet deadlines, problem solving in a crisis, etc. are all great skills in medical regulatory writing. If you don’t have an abundance of professional experience, but you worked on a project where these skills stood out, be sure to mention it.


Not all of us have a “door busting” resume with five pages of extensive industry experience. And that’s OK, as long as you are applying for a job that is appropriate for your level of experience. The golden rule is to present your actual skills in a way that is attractive and easy to understand. That alone demonstrates a proficiency that is important to all medical writing hiring managers: the ability to organize data and information in a clear and concise way. And that’s something I will never undervalue.

Once you have completed your resume, the next step is to get your name out there: Successful Networking in Two Easy Steps

Is your resume ready to get out in the market? Are you ready to apply? Check out our Careers page.

Do you like it?0
May 9, 2019

Are You a Global Medical Device Manufacturer That Is Tired Of Multiple Regulatory Audits? Consider Transitioning To The MDSAP Single Audit

Author: Dr. Suzanne Broussard

MDSAP as a Single Regulatory Audit 

The Medical Device Single Audit Program (MDSAP) is now in year three of voluntarily allowing medical device manufacturers to satisfy requirements of multiple regulatory jurisdictions with a single audit. Understanding the basics of MDSAP is the first step to determining if this is right for your organization.  

Device manufacturers are starting to accept this more harmonized auditing program, with over 2,700 manufacturers having undergone an MDSAP audit as of December 2018 (Figure 1). The significant increase in audits in 2018 reflects Health Canada’s hard deadline of January 1, 2019 for device manufacturers to comply with MDSAP in order to sell medical devices in Canada. While there were plenty of concerns about the transition, Health Canada received over 3,000 MDSAP certifications or transition submissions accounting for 90% of medical manufacturers operating in Canada. The remaining 10% are companies with very low or no sales, meaning they may likely pull out of the market.  

Several early adaptors are lauding the MDSAP program for saving time and limiting company resources needed for auditing agencies. These outcomes are in line with IMDRF’s primary goals for creating MDSAP, which are to “…jointly leverage regulatory resources to manage an efficient, effective, and sustainable single audit program focused on the oversight of medical device manufacturers.”  

If you are one of the many medical devices manufacturers that have not yet embraced MDSAP, industry experts suggest it is time to get started! This single audit via MDSAP provides an opportunity for companies to reap the benefits of reduced audits from agencies in multiple jurisdictions if they sell products in participating countries. 

Keep in mind that MDSAP does not place a single new requirement on device manufacturers. What MDSAP does is place requirements on the Auditing Organizations (AOs) dictating how to consistently perform an audit. Essentially, AOs are approved by regulatory agencies to perform audits after a rigorous process to prove competency. These AOs are charged with performing the audit in a manner that is consistent and predictable while giving a high degree of confidence that the manufacturer is in complete compliance.   

Participating Countries in MDSP
Participating Countries in MDSAP

FDA Touts the Benefits of MDSAP 

Even regulatory authorities like the FDA are promoting the many benefits of MDSAP. 

  • MDSAP routine audits are announced in advance by the scheduling AO and have a pre-established duration. 
  • Manufacturers have one full month to respond to AOs for critical nonconformities (grade 4 and 5) compared to only 15 working days after an FDA inspection. 
  • MDSAP Certification documents may provide a marketing advantage. 

Is Your Organization Ready to Transition to MDSAP?  

Some companies that have gone through the process claim that they found the process easier than going through an FDA audit once they embraced MDSAP. Why? Because, the MDSAP audit is performed in a specific order that is predictable and clearly outlined. This approach is very different than an FDA or ISO audit, which are much less predictable. Company testimonials on the FDA MDSAP site claim transition to MDSAP save costs internally with less disruption.  This sentiment is shared by other industry leaders who applaud the prescriptive nature of the MDSAP audits. 

There are no surprises at MDSAP audits  

IMDRF provides device manufacturers with everything required to understand and prepare for MDSAP. A plethora of resources that explain the program in more detail and help prepare for an MDSAP audit are available on FDA’s website. Best of all—they are free! 

The most helpful resources are the MDSAP Companion Document and the MDSAP Audit Model.  

  • Both these forms provide detailed information that directly corresponds with the MDSAP audit.  
  • There is a section in the documents to explain what should happen at each step of the audit.
  • Requirements are asked by auditors in the order presented and the flow does not vary allowing the manufacturer to better plan the audit.  

If your organization sells medical devices in multiple participating countries and already maintains a high level of compliance, transitioning to MDSAP is worth considering.  Are you ready to ace the MDSAP?

Do you like it?0

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!