This episode of Chasing Compliance is for those working on regulatory submissions for in-vitro diagnostic (IVD) medial devices. Today we talk to our resident Performance Evaluation Report (PER) expert, Bethany Hosford provides suggestions on how to improve your EU IVD regulatory submissions including PERs and their associated documents.

2:15 – Brief background of the In vitro Diagnostic Regulation (IVDR) and the Performance Evaluation Report (PER)

3:15 – Items to tackle prior to beginning to write PER

4:15 – Bethany’s recommendation for starting the PER process

1. Collect as many source documents as possible (eg design files, technical file, risk documentation etc) early int he process.
2. Collect and review all clinical and analytical data available. Try to identify gaps early.
3. Plan the report – what is your strategy? What claims do you need to support? Which General Safety and Performance Requirements (GSPRs) apply?
4. Write your Performance Evaluation Plan (PEP). Clearly characterize your data sources information and strategy for the PER.

6:30 – Tips for finding clinical data or addressing gaps for challenging IVDs. Bethany answers the question, what do you do if you device is mentioned in several articles, but it isn’t a focus?

9:15 – Do you need to consider your audience when preparing a PER? If yes, how should you do that?

10:30 – What is the best approach for reviewing and summarizing data? Should it be done piecemeal or holistically.

12:00 – Tips for writing associated documents such as the Analytical Performance Report (APR), Scientific Validity Report (SVR), and Clinical Performance Report (CPR).

14:10 – What is required to determine scientific and clinical validity in the case of a companion diagnostic (CDx) or other IVD? Where is this information found? BRCA – Gene which is highly associated with the development of breast cancer

18:00 – When is enough data enough? How do you know you have enough clinical data? What if you don’t have clinical data, what should you do?

20:45 – Bethany’s tips for preparing to write a PER. Key takeaways:

1. Understand the scope of your document.
2. Ensure you have a well-defined, MDR/IVDR compliant purpose statement.
3. Identify your claims and make sure you have the data to support those claims.
4. Make sure your data, claims, purpose, and scope are all aligned prior to writing.
5. Ensure you have all appropriate tests and documentation pertaining to the IVD under evaluation.

24:45 – What to do if you find you are missing data or have data gaps during the writing process.

28:45 – What should you do if you don’t fully understand the device you are working on or how to best summarize clinical or analytical data?

30:15 – Summary of topics discussed up to this point and Bethany’s tips for staying organized throughout the PER writing process.

33:45 – Generally, how long does it take to write a PER? What are your tips for pacing?

35:15 – Bethany’s tips for finalizing a PER.

40:00 – What is the value of templates in the PER writing process?

Ready to take your technical writing to the next level, but not sure where to start? Would you like to learn some tips to freshen up your writing approach? In this episode and the next we share more of our favorite tips and tricks for technical writing. Our guide, Jennifer Petrie Signore, PhD has spent years working to become the best and most versatile technical writer possible, and she shares her tips with you. In this episode, we cover a wide range of topics, such as:

• Document review and completion
• Software tools for technical writers
• How to better leverage the tools you use each day
• When to involve your teammates
• How to improve the review process

1:30 – Recap of last episode.

2:30 – What is Jenn’s process for finishing a document.

5:15 – How to make Microsoft Word work for you and speed up your writing process. Jenn discusses tools within word which help improve the writing process, such as:

• Document sections
• Styles tool
• Table properties
• Table anchors
• Page layout (eg landscape and portrait)

9:45 – Other types of software which may help your writing process, such as:

• Excel
• EndNote – Reference Manager
• Perfect It

17:30 – Jenn provides her tips for finalizing documents including how to conduct final editing and revision activities. In summary:

• Step away
• Ask a colleague for help
• Tips for editing and revision.

22:00 – Review as a team effort: tips for leveraging teammates and colleagues. When is it time to hand a document over? When is it appropriate to reach out for feedback?

31:45 – Final thoughts, summary, and wrap-up

Ready to take your technical writing to the next level, but not sure where to start? Would you like to learn some tips to freshen up your writing approach? In this episode and the next we dive into some of our favorite tips and tricks for technical writing. Our guide through the next two episodes is Jennifer Petrie Signore, PhD. From the start of her graduate training, Jenn was focused on becoming the best and most versatile technical writer she possibly could be. In this short series, Jenn shares what she has learned throughout her 15+ years of technical writing experience. In this episode, we cover a wide range of topics, such as:

• Why you should always follow directions,
• The role and value of templates and rubrics,
• The importance of clarity, proper word choice, and succinctness, and
• How to get unstuck or overcome roadblocks when working on long, complex documents.

We cover a lot of information in this episode. If you miss something, we’ve summarized the key points below.

2:00 – Jennifer’s provides some background on her technical and scientific writing training and experience. Jamie and Jenn briefly discuss the importance of writing quality and skill in the technical disciplines and options for training.

10:00 – Are there any general misconceptions or mistakes you would like to address right out of the gate?

1. Take time to learn about the purpose of the document and the audience.
2. Understand and follow the directions or instructions assocaited with the document.

13:25 – Starting the process: how to use templates and instructions to create a strong foundation. Use the template to guide your writing. Make sure you follow the instructions and providing the information the reader is looking for.

19:25 – How to know how much detail to include? When is it time to “go down the rabbit hole?” When is it appropriate to provide a high-level summary? Look for rubrics and previous work. Don’t hesitate to reach out to the client or the audience.

1. How much do they really need to know?
2. How much do they want to know?
3. How much do they already know?
4. What is the scope of the document?
5. Is the information still relevant to the document?

29:10 – The importance of clarity in technical writing. Tips and tricks for improving clarity.

1. Avoid wordy sentences or flower-y language.
2. Let the source documents dictate the content.
3. Do not draw conclusions you cannot support with evidence.
4. As yourself: “Is this still relevant?” “What does this add to the discussion?” “Is it necessary?”

37:40 – Jennifer’s tips for getting unstuck or moving through challenging sections. Leave yourself landmarks.

41:00 – Overall episode summary.

44:00 – What are we going to cover in part 2?

This episode is Part 2 of a two-part episode on Abbreviated New Drug Applications (ANDAs). We continue our conversation with our ANDA expert Sandra Kircus. In this part, Sandra provides advice on how to manage ANDA projects, the importance of strong project management, and provides suggestions for project management tools. She also shares her thoughts on how to regulatory leaders can optimize the ANDA writing process and how to optimize the ANDA process fro companies outside of the United States referred to as xUS companies. Sandra and Jamie discuss why having strong US agent for xUS companies is important. While this advice is focused on xUS companies, it also rings true for US companies as well.

2:30 – Tips for general approach to writing ANDAs

1. Make sure you understand what the agency is looking for
2. Stay focused, don’t give the FDA more than they need or that they are asking for. The level of detail in your regulatory documentation doesn’t need to match the level of detail in your technical documentation.
3. Give yourself flexibility.

5:40 – Tips for the ANDA writing process

1. Put effort into the program management aspect
2. Make sure all contributors and stakeholders are aligned
3. Have periodic discussions with the team
4. Get 1:1 time with the team to discuss the project and specific sections

8:00 – Software for Program Management

10:30 – Proportion of applications from US companies and outside or xUS companies. Implications for xUS companies and role of US agents.

Chasing Compliance: The Global Regulatory Podcast kicks off season two with a two-part episode on abbreviated new drugs applications (ANDAs). Our guest today, Sandra Kircus, walks us through the basics of ANDA submissions, the ANDA approval process, and common challenges associated with ANDA submission. She also touches on the differences between drug applications (NDAs), traditional ANDAs, and petitioned ANDAs. Following this, we discuss agency communication. Agency communication is often considered one of the most challenging and nuanced aspects Chemistry, Manufacturing, and Controls (CMC) regulatory activities. Sandra discusses this in detail in the second half of the episode, providing her perspective on agency communication and some tips for success.

Sandra is a Director in the CMC Division of Global Regulatory Writing and Consulting. Sandra started her career as a chemist in the FDA. After leaving the FDA, Sandra helped several companies establish and maintain regulatory and quality systems. Throughout her 20 year career in the industry, Sandra supported a wide verity of regulatory pathways, however, one of her principal focuses was on CMC-related submissions and submission strategy, including ANDAs. Sandra She holds a B.S. from the University of Montevallo and PhD in Chemistry from UNC Chapel Hill.

2:05 – ANDA Basics

5:05 – What’s the difference between an NDA and ANDA? Sandra provides additional Background on ANDAs.

9:50 – In the case where two companies are simultaneous developing a drug, can one company file an ANDA soon after the other receives approval on a NDA?

12:05 – What are petitioned ANDAs?

15:35 – What does the ANDA approval process involve? What can one expect?

18:55 – Sandra provides several tips for agency communication.

20:15 Tips for 1st time ANDA Submissions

24:15 Communication with the FDA

30:10 – Sandra’s first tips on improving the ANDA preparation and submission process. To be continued in Part 2.

Welcome to clinical site selection and evaluation Part 2, where we continue the conversation on optimizing clinical site selection and evaluation. In this episode Linda Peterson and Julie Sheidy share recommendations on how to approach site selection, how to build teams, how to communicate within organizations and across teams, and their approach to site identification.

Key takeaways include:

1. Sites often look to the CRO or Sponsor for expertise and support. A strong CRO will help the site through selection, accelerating the process.
2. Build your team around the protocol! Therapeutic area experts are needed on both the CRO/Sponsor side and the site side.
3. Anticipation and foresight are key. An experienced Clinical Research Associate (CRA) or Clinical Research Coordinator (CRC) will deeply review the protocol to identify resourcing gaps and determine how to close those gaps early in the site selection process. They will also take the initiative to bring on internal experts or support staff early in the process to address action items within their expertise.
4. Ensure the site has access to the patient population and that the population is willing to support the study.
5. Make sure the site has the infrastructure to set run the study and identify any mismatches or pain points early.
6. Establishing clear lines of communication and setting out roles and responsibilities will make the evaluation process much faster.
7. Yes, checklists are worth it. Both the Site and the Sponsor/CRO will use them as valuable tools and the process will benefit from their use.
8. Contact advocacy groups – they are involved with local, regional, and national communities.
9. Use epidemiological data or incidence data to find areas where the disease is moderately or highly prevalent.

3:00 – How can the site and sponsor work together to accelerate site selection?

5:15 – Julie describes the traits, skills, and characteristics of a “dream team” from CRO or Sponsor perspective and from the site’s perspective.

8:45 – In the event that a CRO or Sponsor identifies a lack of resources at a particular site, is there an advantage to the CRO or Sponsor supplementing those resources?

10:50 – The importance of strong communication within and between the CRO and site “dream teams.”

14:15 – Tips for maintaining a good working relationship and culture through turnover or staffing changes.

16:30 – Best practices for site identification and site selection in the case of rare disease trials and/or common chronic disease trials.

19:15 – How do you address potential site-related bias or the impact of advanced expertise when considering major center or world-class research institutions? How do you ensure the findings are applicable to all care settings if you are conduct research at elite institutions?

20:15 – Can or should sites advocate for altering a protocol or research question to better fit the population or their specific patient population?

This is part 1 on our conversation on optimizing clinical site selection and evaluation. In this episode Linda Peterson and Julie Sheidy provide some background on the process of site selection from both the sponsors or clinical research organizations (CROs) perspective and the site’s perspective. Key takeaways include:

1. Site workload is important. Make sure the site has capacity for your study.
2. Ensure the site has access to the patient population and that the population is willing to support the study.
3. Make sure the site has the infrastructure to set run the study and identify any mismatches or pain points early.
4. Establishing clear lines of communication and identifying roles and responsibilities early will make the evaluation process much faster.
5. Set realistic expectations.
6. Teaching is much more effective than telling. Take the time to help the site or the CRO understand the process or problem.
7. Use checklists!

3:30 – What is the site selection process and what are sponsors looking for?

5:50 – How do you put together a site feasibility questionnaire and where do sponsors begin the selection process?

9:30 – What are the most rate-limiting steps of site selection?

14:30 – What happens if a site does not have the facilities or expertise you need to complete the study? Is it the sponsor’s responsibility or the site’s responsibility to secure that functionality or expertise?

16:25 – Recommendations for what to look for in a clinical site. How do sites evaluate studies they are bringing in?

19:00 – Why it is important to evaluate the community around the site during site selection and do sites search for studies?

20:00 – How do sites facilitate site selection and qualification?

22:00 – A protocol-based workload estimation tool.

24:30 – How do sponsors evaluate how busy sites are? Is it realistic for sponsors to try to evaluate sites workloads during site selection?

28:10 – Julie provides recommendations on how the sponsor or CRO can help with site selection from the site’s perspective.

32:30 – Tips for staying organized and productive during site selection, evaluation, and study startup.

35:00 – How can the sponsor motivate sites to move things forward?

Abbreviations:

CRO = Clinical Research Organization

IRB = Institutional Review Board

CRC = Clinical Research Coordinator

CRA = Clinical Research Associate