Clinical Evaluations are required by the Medical Device Regulation to ensure the safety of devices marketed in the European Union. The requirements are clearly outlined. However, many manufacturers are challenged by 2017/745 and rejections by the reviewers are not uncommon. RCA’s medical device consulting team shares their insights on compiling Clinical Evaluations, including tips from a recent submission.

 

CER & Clinical Evaluation

A clinical evaluation is the assessment and analysis of clinical evidence pertaining to a medical device in order to verify its clinical safety and performance. The clinical evidence is added to the clinical evaluation report (CER) for submission to regulatory bodies. Clinical evaluations are first performed prior to marketing of a medical device and then repeated periodically as new clinical safety and performance information about the device is obtained (e.g. an investigational device).

 

Medical Devices

Medical device companies, as the manufacturer, must demonstrate the device achieves its intended performance. Further, the risks and any adverse events are acceptable when weighed against the medical device manufacturing benefits of the device. Claims made about the device’s performance and safety are supported by suitable evidence or against ISO13485 certification.

 

Clinical Evaluation Example

With regard to a postmarket surveillance clinical evaluation example, manufacturers are expected to implement and maintain surveillance programs which routinely monitor the clinical performance and safety of the device as part of their Quality Management System (QMS). The QMS should use data generated from safety reports for 21CFR 820 documentation. This includes adverse event reports, results from published literature, any further clinical investigations and formal post-market surveillance studies.

 

The stages of a clinical evaluation are outlined in Figure 1, below.

 

Clinical Data

The literature review must be complete, covering pre- and post-market data and any clinical investigations in ISO 14971 certification or EU MDR approval. Common sources for data are:

• Competitive products
• Complaints
• MAUDE database
• Internal clinical testing
• MedWatch
• Published literature using common databases such as PUBMED and Science Direct, etc.

 

EU MDR

In collecting data for EU MDR submission and MDR approval, it’s helpful to print search pages including the search terms and exact logic used in the search. Boolean logic operators such as “AND” and “OR” show repeatability and helps the reviewers in analyzing the resulting clinical evaluation. For published literature, it is not uncommon for thousands of data sources to be identified (especially with medical instruments). In collecting data, it’s helpful to print search pages including the search terms and exact logic used in the search.

 

Data Evaluation

After data collection, the next step is assessing content and determining whether the data is considered for the clinical evaluation. A scoring table can be useful for determining whether or not to include data. For example, the data might be scored on factors such as device equivalency, application equivalency, similarity of operator and demographic equivalency.

 

Clinical Studies

Studies which pass the scoring table must be summarized on how they support the Essential Requirements (see Figure 1 above). A common mistake is simply copying the conclusion of the study instead of describing how it relates to the Essential Requirements. The clinical evaluation must be re-creatable by third parties based on the process and scoring system outlined in the report. If the notified body can’t re-create it, they have no recourse except to find deficiency in the medical manufacturing.

 

Regulatory Affairs

Make it easy for the reviewers to check off each step. Highlight what they are looking for relative to what you are covering. Refer to guidance and standards such as, The European Commission: Clinical Evaluation: a guide for manufacturers and notified bodies¹ which features helpful appendices.

Common Errors:

• Missing inclusion / exclusion criteria
• Omitting applicable papers
• Summarizing papers instead of evaluating them. Although a summary is required, the more important (and often omitted) portion is to explain how the data supports the Essential Requirements.
• Forgetting summary tables
• Forgetting a concluding argument. Explain how the document fulfills the requirements for the clinical evaluation.

 

Conclusion

Clinical evaluations include the CER, assessment, and analysis of the medical device’s clinical data to verify its clinical safety and performance. The stages are well-defined but can be intensive. A thorough clinical evaluation can involve thousands of data sources and significant time for proper assessment. Manufacturers should submit evaluations that are re-creatable and make it easy for reviewers to follow. Make it easy for the reviewers to check off each step. Highlight what they are looking for relative to what you are covering.

 

About RCA’s Medical Device Consulting Services

The regulatory process surrounding the medical device industry involves strict adherence to pre/post-market compliance throughout a device’s life cycle. Even a single compliance issue you have can turn into a significant effect on your business. RCA’s medical device consultants can help guide you through any stage of this strategic process, with capabilities during product development through the regulatory clearance/approval of your product.

Our team of over 500 industry experts — including former FDA officials and other leaders in the field of medical device regulation — will work with your company to create a quality assurance and regulatory compliance approach tailored to your products and regulatory needs. RCA works with both international Fortune 100 companies and small local start-ups, as well as law firms requesting remediation for warning letters, 483’s, import bans, or consent decrees.

 

Cybersecurity

For medical device manufacturers, technology can be a double-edged sword. The innovative technologies that elevate the quality of life for patients can also be used to potentially undermine the organization using the device. The consequences can affect the device itself if we do not implement good IoT cybersecurity and FDA cybersecurity protocols. At Regulatory Compliance Associates Inc.®, we offer a wide variety of services for medical device security to help ensure that your product is protected from cyber-attacks.

With a well-planned design, along with full visibility of product development and the supply chain, RCA can help strengthen your device’s cybersecurity posture throughout. We partner with medical device companies for the entire life cycle, including from the development of your product to the regulatory submission to your notified body.

 

Regulatory Affairs

Regulatory affairs is Regulatory Compliance Associates^® Inc.’s backbone, and we handle more submissions in a month than many manufacturers do in a lifetime. We have experience working with the FDA, global regulatory bodies and/or agencies, and notified bodies worldwide. Therefore, you can count on us for in-depth and up-to-date insights which increase speed-to-market.

As a trusted regulatory affairs consultant, our FDA veterans and industry experts are here to help you navigate the difficulties associated with new product submissions. They have expertise in both the approval process and post-approval support. 

• New Product Approval
• Post-Approval Support
• Outsourced Staffing
• EU MDR

 

Compliance Assurance

Increasingly, life science companies are feeling the pressure of greater scrutiny by regulators, and responding by developing sustainable compliance strategies. Whether it’s preparing for an audit, developing a response to an FDA finding, or remediation for an adverse event, Regulatory Compliance Associates can help.

Our network of over 500 FDA veterans and industry professionals offers a unique blend of expertise that allows us to handle both simple and complex regulatory compliance challenges within the medical device industry.

• Gap Assessments
• Internal Audits
• Employee Training
• Notified Body Response

 

Quality Assurance

Regulatory Compliance Associates^® Inc.’s Quality Assurance services include quality system assessments, strategy, implementations, and identification of quality metrics to ensure continuous improvement, aligning with your business needs and goals. Our consultants are quality experts with experience spanning major corporations and start-ups. We know firsthand how to achieve, maintain, and improve quality, and we excel in transferring this knowledge to your organization.

In the medical devices field, quality assurance (QA) is more than merely ensuring the quality of a finished product. You need the tools to monitor and regulate every process from the design of a new product to continued quality compliance as the device is sent to market. At RCA, we offer you the assistance you need to monitor these processes and ensure quality compliance every step of the way.

With more than 15 years of experience as a trusted medical device quality assurance consultant, our team of over 500 industry experts and FDA veterans is fully equipped to handle your unique QA needs.

• ISO13485 
• 21 CFR 210
• 21 CFR 211
• Outsourced Staffing
• MDSAP
• Facility Validation
• Equipment Validation

 

Remediation Support

Regulatory Compliance Associates^® Inc. is widely recognized within the life science industry and global regulatory agencies for its ability to help companies successfully resolve complex regulatory challenges, including remediation. With a proven track record of success, we have significant experience with the development of responses to 483 Observations, Warning Letters, Untitled Letters, and Consent Decrees.

Our value goes beyond the initial response by helping companies successfully execute their action plans, develop an improved compliance culture tailored to the needs of their business, and ultimately move beyond the regulatory action to emerge as a stronger business. We negotiate difficult demands of remediation with insight and the clear advantage of our unique expertise and experience that makes partnering with Regulatory Compliance Associates a competitive differentiator in the remediation space.

• Quality System
• Technical File
• Design History File
• Data Integrity
• cGMP 

 

Strategic Consulting

Whether it’s a strategy, a technical plan, or a project, Regulatory Compliance Associates^® Inc.’s worldwide experience can help ensure a successful mix of people and products so your project is on time, on budget, and you’re never embroiled in a costly mistake.

Our 500 industry and FDA experts are here to provide the unique insight you need before an M&A deal, through a staffing crisis, and in every area of your product’s development and life cycle. As the trusted medical device manufacturing consultants of thousands of companies around the world, we have the knowledge and expertise needed to deliver exceptional results to your business — no matter your size or unique needs.

• Manufacturing Optimization
• Product Lifecycle Management
• Mergers & Acquisitions (M&A)
• Due Diligence
• Device Vigilance
• Product Complaints
• Medical Information

 

About RCA

Regulatory Compliance Associates^® (RCA) provides FDA inspection consulting services to the following industries for resolution of compliance and regulatory challenges:

• Pharmaceutical
• Biologic & Biotechnology
• Sterile compounding
• Medical device
• Lab Testing

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA, Health Canada, MHRA and globally-regulated companies.

As your partners, we can negotiate the potential minefield of regulatory compliance and regulatory due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

• Founded in 2000
• Headquartered in Wisconsin (USA)
• Expertise backed by over 500 industry subject matter experts
• Acquired by Sotera Health in 2021

 

About Sotera Health

The name Sotera Health was inspired by Soteria, the Greek goddess of safety, and reflects the Company’s unwavering commitment to its mission, Safeguarding Global Health^®.

Sotera Health Company, along with its three best-in-class businesses – Sterigenics^®, Nordion^® and Nelson Labs^®, is a leading global provider of mission-critical end-to-end sterilization solutions and lab testing and advisory services for the healthcare industry. With a combined tenure across our businesses of nearly 200 years and our industry-recognized scientific and technological expertise, we help to ensure the safety of over 190 million patients and healthcare practitioners around the world every year.

We are a trusted partner to more than 5,800 customers in over 50 countries, including 40 of the top 50 medical device companies and 8 of the top 10 pharmaceutical companies.

 

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