Systematic literature reviews are a central component of Clinical Evaluation Reports. However, searching multiple databases, screening thousands of titles, extracting structured data and preparing audit-ready documentation often absorbs the author’s time and delays progress. When used responsibly, AI can accelerate these repetitive tasks while preserving reproducibility and traceability.

Common Bottlenecks in Traditional SLRs

Teams frequently encounter the same constraints:

• Running inconsistent and inadequate queries across databases and managing large duplicate sets.
• Manual title and abstract screening that consumes significant SME/author hours.
• Extracting study-level fields such as design, population, endpoints and harms into a consistent dataset.
• Producing PRISMA-style documentation, version control and traceability for audits and Notified Body review.

These efforts are essential for MDR compliance but can also significantly impact timelines and quality.

What AI Contributes, with Safeguards

AI is most valuable for repetitive, pattern-based work. Key capabilities that benefit SLRs include:

• Automated retrieval and de-duplication across multiple sources.
• Assisted screening that ranks records by relevance, keeping reviewers in control.
• Rapid structured extraction into a standardized data dictionary.
• Automatic generation of PRISMA flows and exportable audit trails.

AI should extend human capability, not replace it. Every AI generated result must link back to the source and remain verifiable by reviewers.

A Regulator-Ready Hybrid Workflow

Below is a practical sequence that balances automation with mandatory human checks:

• Scope and protocol: Define the clinical questions, populations, comparators and acceptance criteria; pre-register search strings, databases and date ranges.
• Automated retrieval and clean-up: Run pre-registered searches, remove duplicates and tag records for screening.
• Assisted screening with adjudication: Use AI scoring to assess records; two reviewers confirm inclusions and resolve disagreements.
• Full-text extraction and verification: AI extracts data based on pre-defined instructions into templates; reviewers verify critical fields such as endpoints and harms.
• Quality appraisal and synthesis: Appraise study quality, apply pre-defined criteria for benefit-risk, and conclude study findings accordingly.
• PRISMA output, traceability and version control: Produce a PRISMA flow diagram, an exportable study table and a traceability matrix linking claims to evidence and risk controls.

This approach reduces the human oversight regulators expect while automating the steps that typically consume the most time.

Mini Case Example

Consider a typical SLR for a Class IIa device that searches five databases and returns 3,500 records. In a manual workflow, title/abstract screening and full-text extraction might require four to six weeks of an SME’s time. With automated retrieval, de-duplication and assisted screening, the initial screening pool can be reduced by more than half within days. Assisted extraction then populates a structured dataset that SMEs can validate in a matter of days rather than weeks. Deliverables such as the PRISMA flow and an exportable study table. The net effect is savings of several weeks in SME time, faster responses to Notified Body queries and a cleaner audit record that documents reviewer verification of AI-extracted items.

Integrating Real-World and Decentralized Data

Regulatory reviewers increasingly expect real-world evidence, registries and decentralized trial outputs to support CER updates. AI can help harmonize heterogeneous inputs by tagging metadata, tracking sources and converting registry exports into structured records for appraisal. The same human-in-the-loop principles apply here, and the analytical validation and reviewer verification are required before RWE is used in benefit-risk conclusions.

Operational Benefits

Adopting this hybrid model delivers measurable improvements:

• Shorter cycles because searches, de-duplication and extraction are automated.
• Fewer data-entry inconsistencies due to structured extraction.
• Better audit readiness through consistent PRISMA outputs and per-item provenance.

These gains free the author and the subject experts to focus on interpretation and clinical judgment rather than repetitive data handling.

Governance and Team Readiness

Introducing AI in your workflow should include clear guidelines. Define standard operating procedures specifying where AI is permitted, which fields require mandatory human verification, and how AI determined scores should be interpreted. Train reviewers to identify common AI errors and record corrections. Periodic audits comparing AI outputs with manual benchmarks help maintain quality and build trust with internal stakeholders and external reviewers.

Below is a quick SLR Checklist when automation is used

• Pre-specify search strategy and inclusion/exclusion criteria in a protocol.
• Utilize exportable, audit-ready outputs including PRISMA flows and data dictionaries.
• Keep reviewers in the loop for screening and extraction verification.
• Maintain a traceability matrix linking claims, evidence and post-market outputs.
• Archive logs showing search timestamps, reviewer decisions and data sources.

How CAPTIS^® Can Help

Integrated platforms that combine literature search, collaborative review, structured extraction and automated reporting make this hybrid workflow practical on scale. CAPTIS^® automates extraction, generates audit-ready reports and preserves references while enabling simultaneous review and simple cross-verification. Features that accelerate compliance include an integrated citation manager that links each extraction to source documents, exportable audit logs for every reviewer decision, role-based review workflows and pre-built templates for traceability matrices. That mix helps teams shorten SLR cycles without sacrificing traceability or regulatory rigor. Read How AI Speeds Up Systematic Literature Reviews by 60% blog here.

Conclusion

A rigorous protocol, clear reviewer responsibilities and tools that produce verifiable outputs make it possible to utilize automation and reduce SLR timelines while improving consistency and auditability. Teams that adopt a balanced AI-plus-reviewer approach will be better positioned to meet Notified Body expectations and keep CERs current with high-quality evidence. By leveraging AI-powered tools like CAPTIS^®, medical device professionals can ensure compliance with regulatory requirements while saving time and resources. Stay ahead of the curve by embracing AI in your SLR process. See how our AI-powered solutions can transform your regulatory processes. Contact us at info@celegence.com to learn more.

As the EU MDR transition deadlines for legacy devices approach, dental device manufacturers face a heightened burden of clinical evidence. In a recent webinar hosted by Celegence, regulatory experts Priya Ray Chaudhuri and Dr. Manaswitha Boyanagari shared hard-earned lessons from working with dental clients through MDR transitions — and offered clear guidance on how to navigate the clinical evaluation process with confidence and precision.

Here are the key takeaways that regulatory and clinical leaders should prioritize when preparing dental device submissions under MDR.

Why Dental Devices Face Increased Scrutiny

Unlike many other device categories, dental products — particularly implants and restorations — directly interact with human tissue, integrate into bone, and often remain in the body permanently. This raises biological risks — such as inflammation, mechanical failure, or peri-implantitis and Bone loss, making robust clinical evidence not just a regulatory expectation, but a public health necessity.

Certain dental devices have also been reclassified under MDR compared to the earlier MDD framework. Devices previously considered low- to moderate-risk under MDD — for example: Dental implants, Bone replacement materials especially if they have a biological effect or are wholly or mainly absorbed, and certain software tools — are now Class IIb or even Class III. The result? New conformity assessments for all medical devices currently circulating within the European Union Member States, complying with the new regulation and new rules. No grandfathering. Manufacturers must justify safety and performance through new, MDR-aligned clinical evidence and additional requirements like submission of implant cards and summary of safety and clinical performance (SSCP) for implantable and Class III devices.

Clinical Evaluation: A Lifecycle, not a Checkbox

In the webinar, Celegence emphasized the need for a lifecycle approach to clinical evaluations, anchored in four key documents:

• Clinical Evaluation Plan (CEP): Defines the claims, population, data sources, and appraisal methods. It’s the foundation for all subsequent activities.
• Clinical Evaluation Report (CER): Synthesizes clinical data, assesses benefit-risk, and demonstrates alignment with the GSPRs.
• State of the Art (SOTA) Review: Establishes the baseline for comparison and benchmarks claims against current best practices.
• Post-Market Clinical Follow-up (PMCF): A must-have for most Class IIb and III devices, PMCF provides real-world evidence to support long-term safety and performance.

Building a Robust Evidence Strategy

Most manufacturers won’t have the luxury of new clinical trials, especially for legacy devices. That makes literature appraisal the backbone of many MDR submissions.

So, it’s important that manufacturers:

• Be precise in defining intended use and claims. Vague terms like “safe” or “effective” won’t pass. Quantify outcomes where possible — e.g., “98% survival at 7 years” — and ensure they match the indications and target population.
• Design a thorough literature strategy. Use smart filters, search across multiple databases, and include gray literature or implant registries. For dental products, state-of-the-art evidence is particularly critical due to variability in patient response and device longevity.
• Critically appraise sources. Not all literature is created equal. Use a scoring matrix based on relevance, quality, and alignment with the device in question. The MIDDEF 2.7/1 guidance remains a good starting point.

Common Pitfalls — and How to Avoid Them

Manufacturers frequently run into the same issues when preparing MDR-ready CERs:

• Claims not linked to evidence. Every claim should tie back to a data point. If the evidence is lacking, that gap must be addressed through PMCF — not ignored.
• Over-reliance on equivalence. MDR has raised the bar for demonstrating equivalence, especially in terms of material and technical characteristics. A titanium implant is not equivalent to zirconia just because they’re both biocompatible.
• Outdated SOTA reviews. Even legacy devices need updated benchmarking. SOTA evidence should typically be refreshed every 12–24 months.
• PMCF treated as an afterthought. PMCF should be risk-driven and strategic, not just a box-checking exercise. Well-designed clinician surveys, registry tracking, or focused case studies can provide meaningful insights — and address notified body feedback proactively.

What Executive Teams Should Take Away

For dental manufacturers, MDR compliance is more than just a regulatory obligation — it’s a strategic imperative. Clinical evaluations must now go beyond generic templates or legacy data. Success requires structured, defensible, and up-to-date documentation.

Leadership teams should ensure they’re resourcing regulatory functions appropriately — with expert partners, robust data collection systems, and cross-functional input from product development and clinical affairs. A well-executed clinical evaluation strategy not only satisfies regulators, it strengthens a company’s competitive standing in a market where performance, aesthetics, and safety all drive success.

Partner With Celegence

MDR clinical evaluations for dental devices don’t need to be overwhelming. With expert support and proven methodologies, you can deliver CERs, SOTAs, and PMCF strategies that align with regulatory expectations and stand up to Notified Body scrutiny.

Work with our regulatory specialists today and simplify your path to MDR compliance with confidence.

In today’s fast-moving MedTech world, regulatory missteps aren’t just setbacks—they’re risks to patient safety, product reputation, and market success. With the FDA’s Medical Device Reporting (MDR) requirements becoming more complex, staying compliant is no longer optional; it’s a strategic imperative.

At Celegence, we help medical device manufacturers turn MDR compliance into a competitive advantage—with expert-driven strategies, streamlined systems, and scalable support tailored to your organization’s needs.

Why FDA MDR Compliance Can’t Be an Afterthought

If you’re marketing a device in the U.S., FDA MDR (21 CFR Part 803) requires you to report adverse events, serious injuries, deaths, and certain malfunctions quickly and accurately. These reports provide critical post-market surveillance data that help regulators monitor device safety and protect patients.

Non-compliance comes with serious consequences, including:

• FDA warning letters that can disrupt your operations
• Civil monetary penalties that can escalate rapidly
• Costly recalls and associated logistics, legal, and reputational fallout
• Loss of market trust that impacts both patients and healthcare providers

For medical device manufacturers, the real cost isn’t just regulatory—it’s also the risk of losing credibility in a market where safety and reliability drive purchasing decisions.

The key to staying ahead lies in your systems, training, and strategic partnerships that ensure compliance is embedded in your operations from day one.

Celegence: Your Partner in Proactive MDR Compliance

Whether you’re launching a new device or scaling across markets, Celegence provides tailored MDR support that meets you where you are—and takes you where you need to go. We combine regulatory expertise, process optimization, and advanced technology to create MDR systems that are reliable, repeatable, and ready for audits.

Here’s how we help you build a future-proof MDR compliance strategy:

• Adverse Event Reporting Strategy – Expertly structured workflows to ensure you meet reporting deadlines without errors or omissions.
• Gap Assessments – Identify risk points in your current process before the FDA does, reducing exposure.
• QMS & Complaint Handling Integration – MDR seamlessly embedded into your Quality Management System for smoother operations.
• Audit-Ready Documentation – Organized, consistent, and accessible records that withstand regulator scrutiny.
• Team Training & Change Management – Equip teams with up-to-date regulatory knowledge and practical tools to execute confidently.
• Global PMS Alignment – Align FDA MDR processes with EU Vigilance and other international post-market requirements for global compliance consistency.
• Cross-Functional Communication Enablement – Facilitate seamless collaboration across quality, regulatory, clinical, and technical functions, as well as distributors and affiliates worldwide.

By embedding MDR requirements into every stage of your product lifecycle, we help you protect patients while safeguarding your business objectives.

Common MDR Issues (And How We Help You Avoid Them)

Many manufacturers struggle with MDR implementation because compliance isn’t just about reporting—it’s about building the right systems and culture. Common issues include:

• Misclassifying reportable events leading to under-reporting or over-reporting
• Annual entry errors in Form 3500A submissions that create inconsistencies
• Inconsistent timelines and failure to meet the 5- or 30-day reporting windows
• Missing documentation that weakens audit readiness
• Poor SaMD (Software as a Medical Device) traceability for patches and upgrades
• Disconnected QMS and complaint handling processes that cause reporting delays

Celegence closes these gaps by bringing together people, processes, and technology. Our experts not only interpret regulations but also translate them into practical systems your teams can execute.

MDR & SaMD: What You Don’t Know Can Hurt You

Software-driven devices bring unique reporting challenges. The FDA continues to refine expectations for SaMD, particularly as cybersecurity risks and human factors gain attention. Issues such as software glitches, corrupted data, or confusing user interfaces can directly impact patient safety and fall under MDR requirements.

We help you strengthen your SaMD compliance by:

• Mapping software risks to MDR reporting requirements to ensure no gaps
• Building traceability for patches and version control so every change is documented
• Identifying cybersecurity vulnerabilities that may trigger mandatory reporting
• Training teams on red flags unique to software such as UI misuse, algorithm errors, or integration failures

By addressing SaMD-specific risks, we enable you to stay compliant while keeping pace with fast-moving software updates.

MDR Compliance That Powers Better Products

A strong MDR program doesn’t just keep regulators satisfied—it strengthens your entire product lifecycle. Proper reporting and data analysis fuel better design, smarter risk management, and continuous product improvement.

With Celegence, you can:

• Leverage MDR data to detect trends, usability issues, and recurring malfunctions early
• Strengthen ISO 13485 and ISO 14971 alignment by integrating MDR into risk and quality frameworks
• Drive continuous improvement across your portfolio, reducing the likelihood of repeat issues
• Improve customer trust by demonstrating a proactive commitment to safety and compliance

In short, MDR compliance becomes not just an obligation but a driver of innovation and market success.

Building Confidence in FDA MDR Compliance

MDR compliance is more than ticking regulatory boxes—it’s about protecting patients, building trust, and enabling growth. With FDA requirements under constant scrutiny and global markets demanding alignment, medical device companies cannot afford to take chances.

At Celegence, we partner with MedTech innovators to turn compliance into a strategic advantage. By combining expert guidance, proven systems, and scalable technology, we help you achieve confidence in MDR compliance—today and in the future.

Contact us at info@celegence.com to learn how our expert services and solutions can strengthen your reporting processes, improve audit readiness, and ensure ongoing compliance.

The regulatory environment for medical devices continues to evolve at a rapid pace. With increasingly stringent requirements under the EU MDR, specific expectations in global markets, frequent updates to regulatory standards, and the complexity of high-risk device portfolios, manufacturers are facing greater challenges than ever in aligning their compliance strategies.

Our recent webinar brought together expert insights on how manufacturers can strategically navigate the evolving regulatory landscape by strengthening their clinical evaluation processes, maintaining audit readiness, leveraging digital tools such as CAPTIS®, and embracing future-focused regulatory foresight.

The Foundation: Understanding the Impact of Regulatory Divergence

Regulatory divergence refers to the differences in medical device requirements and approval processes across countries and regions. These variations impact product development, market access, clinical testing, and launch timelines. Understanding and managing these differences is key to ensuring compliance, accelerating time-to-market, and staying competitive globally.

The Role of Clinical Evaluation in Compliance

A well-defined clinical strategy is indispensable for meeting the diverse regulatory requirements worldwide. Clinical evaluation ensures evidence is purposeful, aligned with the device’s intended use, and effectively supports safety and performance claims. Clinical evaluation plays a crucial role in maintaining ongoing compliance by:

• Supporting successful Notified Body audits
• Reinforcing alignment to evolving regulatory standards
• Mitigating risks of delays or non-conformities.

Leveraging Technology to Drive Efficiency and Accuracy

Technology integration is a strategic advantage for achieving regulatory compliance and audit readiness. Solutions such as Celegence’s CAPTIS® leverage automation, AI, and structured content management to streamline documentation and regulatory workflows.

These digital tools offer:

• Improved Data Management: Better version control and organization reduce errors and duplication of effort
• Process Automation: Automating repetitive tasks speeds up document creation and review
• AI-Driven Evidence Analysis: AI can sift through vast volumes of clinical literature, extracting relevant data accurately and efficiently—a task that is particularly valuable for high-risk devices with complex evidence requirements.

While AI accelerates processes, experienced regulatory professionals remain essential for oversight, quality assurance, and final decision-making within a human-in-the-loop model.

Audit Readiness

Audit readiness is often viewed as a challenging but essential pillar for compliance throughout the medical device lifecycle. A structured, proactive approach can ensure manufacturers are prepared for both scheduled and unannounced regulatory inspections. Key components include:

• Pre-Submission Consultation: Consulting with notified bodies and regulatory experts early helps identify documentation gaps and align with regulatory requirements, reducing submission delays or rejections
• Comprehensive Documentation: Maintaining organized, complete, and up-to-date technical files, clinical evaluation reports (CERs), risk management files, and post-market surveillance plans is critical. These documents must be audit-ready—formatted and accessible to facilitate efficient review
• Team Training and Awareness: Everyone involved, from regulatory affairs to quality assurance, technical and clinical teams, must be well-trained in relevant regulatory requirements and their specific roles during the audits. Familiarity with internal procedures and confident responses to auditors’ inquiries strengthen audit readiness
• Traceable Evidence: Demonstrating compliance requires clear, traceable documentation aligned with regulatory standards, including clinical data, conformity assessments, and risk-benefit analyses
• Communication and Logistics: Planning the audit schedule, ensuring key personnel availability, preparing facilities, and establishing audit response protocols all contribute towards smooth inspections
• Mock Audits: Conducting internal or third-party mock audits acts as a rehearsal, revealing gaps in documentation or processes and enabling corrective actions to be taken ahead of formal audits.

Future-Proofing Compliance: Regulatory Foresight

The regulatory landscape is dynamic, with frequent updates and evolving expectations—especially in medical devices and digital health sectors. Staying compliant requires a proactive approach which involves not just reacting to changes but anticipating them.

Manufacturers who embed regulatory foresight into their strategies can:

• Innovate confidently
• Respond swiftly to regulatory changes
• Maintain trust with Notified Bodies and end users.

Proactive monitoring of guidance documents and standards, coupled with early integration of regulatory changes, reduces compliance risks and positions manufacturers for long-term success.

Key Takeaways

• Harmonized and comprehensive EU MDR documentation can be leveraged for other regulatory submissions with minimal modifications, improving operational efficiency and reducing compliance costs
• Technology platforms, including AI tools, significantly reduce manual effort and increase accuracy in documentation and evidence analysis
• Human expertise remains essential to interpret AI-generated outputs and make informed regulatory decisions
• Audit readiness is fundamental for seamless Notified Body audits and maintaining regulatory compliance
• Clinical evaluation is the compass guiding compliance efforts and ensuring patient safety
• Regulatory foresight is a necessity in a rapidly evolving environment to sustain market presence and innovation.

Final Thought

Compliance is not a one-time occurrence but an ongoing journey. Robust clinical evaluation combined with strategic use of technology and a future-focused mindset equips manufacturers to navigate this journey with greater confidence.

As echoed in our webinar:
“Compliance is a journey, and robust clinical evaluation is your compass.”

By adopting these principles, medical device manufacturers can meet regulatory expectations, enhance operational efficiency, and most importantly, ensure patient safety.

What is Adverse Event Reporting (AER)?

The process of Adverse Event Reporting (AER) involves the systematic recording and submission of information about adverse events that occur during the use of medical products (drugs, devices and vaccines) Such reports contribute significantly to the surveillance of product safety by regulatory agencies, allowing for prompt action when needed to ensure public health and safety.

Importance of Reporting in Medical Devices

Adverse events are any unexpected, harmful or untoward medical occurrence related to the use of the medical product in humans not necessarily caused by the product. Reporting of adverse events in medical devices is a critical part of post-market surveillance aimed at ensuring the continued safety and performance of medical devices after their use. This includes the identification, documentation and reporting of incidents in which the device may have caused or contributed to injury, death or malfunction. Adverse events can be reported by manufacturers, importers, distributors, healthcare providers and patients/consumers.

Reporting Requirements and Key Information

Reporting requirements for adverse events (AEs) vary according to jurisdiction, type of organisation and severity of the event. Serious incidents causing death, serious injury or deterioration of health; requiring medical or surgical intervention or causing permanent impairment should be reported. A recurring device malfunction which has the potential to cause serious harm should be reported. The regulatory authorities usually require information related to reporter, device, date of occurrence, description of the events, outcome and severity. If the reporter is a manufacturer, details related to corrective and preventive actions, recalls, field safety corrective actions, if any are also required. when a medical device adverse event report is submitted. The objective is to present a comprehensive and unambiguous image of the event, device, and patient outcome.

Global Regulatory Frameworks and Reporting Systems

Every nation has set up a different regulatory framework with distinct reporting procedures, specifications, and deadlines for tracking and handling incidents involving medical devices. Manufacturers, medical professionals, and regulatory affairs specialists working in a global market must comprehend these distinctions.

United States – FDA

The Food and Drug Administration (FDA) is in charge of regulating medical devices in the US. The Manufacturer and User Facility Device Experience (MAUDE) database and the MedWatch application are the main reporting platforms. Adverse events must be reported by manufacturers, importers, and device user facilities in accordance with the Medical Device Reporting (MDR) regulation (21 CFR Part 803). The eMDR system must be used to electronically submit reports. The FDA mandates that events requiring immediate corrective action be reported within five workdays, and that serious injuries or deaths be reported within thirty calendar days. The FDA can respond promptly to safety communications and recalls thanks to this strong system. The TPLC and MAUDE database searches are integrated in CAPTIS® platform of Celegence. It enables the medical writers to seamlessly conduct database searches and analysis of the search results to obtain quality outcomes.

European Union – EUDAMED

The Medical Device Regulation (EU) 2017/745, which requires the reporting of serious incidents and field safety corrective actions, governs medical devices in the European Union. EUDAMED (European Database on Medical Devices) is the EU’s central database for medical device vigilance. Incidents must be reported by importers, manufacturers, and authorized representatives; patients and healthcare providers may voluntarily report through the appropriate national authorities. The deadlines are strict: death or a major decline in health must be reported within two days, major public health threats must be reported right away, and other serious incidents must be reported within ten to fifteen days.

United Kingdom – MHRA

The Medicines and Healthcare Products Regulatory Agency (MHRA) was the regulatory pathway that the United Kingdom established. Systems like the Manufacturer’s Online Reporting Environment (MORE) and the Yellow Card Scheme are still used in the UK to report adverse events. Within a certain amount of time—two days for public health threats, ten days for fatalities or serious injuries, and fifteen days for other reportable incidents—manufacturers and their UK Responsible Persons are required to report serious incidents.

Canada – Health Canada

Health Canada is in charge of medical device safety in Canada through the Medical Device Problem Report system and the Canada Vigilance Program. According to the law, distributors, importers, and manufacturers must report unfavorable incidents. Timelines for reporting incidents are set at 30 days for other incidents and 10 days for events that pose a serious risk. Reports may be submitted via specified forms or electronically.

Australia – TGA

The Incident Reporting and Investigation Scheme (IRIS) is run by the Therapeutic Goods Administration (TGA), Australia’s regulatory body. According to Australian laws, healthcare providers may choose to report adverse events voluntarily, but sponsors—including importers and manufacturers—must report them. According to severity, the reporting deadlines are tier-based: two days for major public health threats, ten days for major injuries or fatalities, and thirty days for less important incidents.

Japan – MHLW and PMDA

Medical device vigilance in Japan is a joint responsibility of the Ministry of Health, Labor, and Welfare (MHLW) and the Pharmaceuticals and Medical Devices Agency (PMDA). Marketing authorization holders can report more easily thanks to the J-MEDWATCH system. If an adverse event is considered serious, it must be reported within 15 days; for less serious incidents, reporting must be done on a regular basis. The highly structured regulatory environment in Japan places a strong emphasis on traceability and documentation.

China – NMPA

Adverse event reporting in China is regulated by the National Medical Products Administration (NMPA) via a national electronic monitoring system. Manufacturers, holders of marketing authorizations, and healthcare facilities are required to report. For other kinds of incidents, regular safety updates are necessary, and serious adverse events must be reported within 15 days. In recent years, China’s regulatory framework has undergone significant modernization, bringing it closer to international norms.

India – CDSCO

The Materiovigilance Programme of India (MvPI) is run by the Central Drugs Standard Control Organization (CDSCO), India’s regulatory body, to keep an eye on adverse events linked to medical devices. While hospitals and medical professionals voluntarily participate through Adverse Drug Reaction Monitoring Centers (AMCs), manufacturers and importers are obligated to report incidents. India strives to conform to international reporting standards, despite the fact that timelines are not as clearly stated as in other nations.

Global Challenges in Adverse Event Reporting

A crucial but difficult part of international health systems is the reporting of adverse events for medical devices. A number of factors, including underreporting, inconsistent regulatory frameworks, divided responsibilities, technological constraints, and cultural considerations, contribute to the complexity. A diversified strategy is needed to address these issues, including coordinating global standards, making investments in digital infrastructure, encouraging a transparent and safe culture, and utilizing advanced analytics to improve signal detection.

The Role of Technology in Adverse Event Management

The application of advanced technologies, such as Artificial Intelligence (AI) and Machine Learning, is being investigated for their potential to augment signal identification and pattern recognition within extensive AE (Adverse Event) databases. Furthermore, the fusion of AE documentation with Electronic Health Records (EHRs) can automate data acquisition, alleviate the workload of clinicians, and enhance the precision of the data.

Toward Safer and More Reliable Medical Devices

In conclusion, medical device adverse event reporting is essential to patient safety and preserving the integrity of healthcare systems. It facilitates prompt regulatory actions and ongoing product development by gathering real-world data on device performance and related risks. Its efficacy is hampered by issues like underreporting, disjointed regulatory frameworks, and poor technological integration. In order to get past these obstacles, manufacturers, medical professionals, regulators, and patients must work together. Post-market surveillance will be strengthened and everyone will eventually have access to safer and more dependable medical devices thanks to the development of digital reporting systems, the standardization of international standards, and the promotion of an open culture.

Contact us today at info@celegence.com to learn how we can help your team with global adverse event reporting and strengthen your medical device compliance strategy.

Once a product is confirmed as a combination product, the next step is identifying its Primary Mode of Action (PMOA). This is defined as the single mode of action that provides the most important therapeutic effect of the product.

If the product’s intended therapeutic benefit is primarily achieved through a chemical or metabolic interaction, then it is typically drug-led. If the effect is driven by physical means, such as mechanical support or energy transmission, it is considered device-led.

The PMOA determines which FDA center will lead the regulatory review. For example:

• Drug-led products are generally reviewed by the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER).
• Device-led products fall under the purview of the Center for Devices and Radiological Health (CDRH).

Understanding this distinction is crucial because it dictates the regulatory submission pathway, data requirements, and even post-approval compliance expectations.

Comparing Drug-Led and Device-Led Pathways

To illustrate the regulatory differences, the table below outlines key contrasts between the two classifications:

In cases where the PMOA is not obvious, the FDA may determine the lead center based on precedent or safety and effectiveness concerns. This is why early interaction with the FDA is strongly encouraged.

Gray Areas and Borderline Scenarios

Innovative therapies don’t always fit neatly into predefined categories. Consider, for example, a therapeutic powder that forms a gel upon hydration and controls the release of a drug physically, without any chemical reaction. While it may appear to be a simple formulation, the polymer mechanism may qualify as a device component. In such borderline cases, even the excipient could be classified as a regulated device.

Another emerging gray area involves digital health integrations. Take the example of an antipsychotic pill embedded with an ingestible sensor to track adherence. Although the drug provides the treatment, the device aspect introduces complexity in classification. FDA treated this as a drug-led combination product with additional review of the device software and hardware elements.

Sponsors dealing with similar situations should not assume a default classification. Instead, they should seek clarity from the FDA early, using the pathways discussed below.

Engaging the FDA: RFD and Pre-Submission Pathways

To avoid ambiguity and regulatory missteps, the FDA offers sponsors two main avenues for determining classification:

1. Request for Designation (RFD)
   The RFD is a formal process through which the sponsor asks the FDA’s Office of Combination Products (OCP) to determine whether the product is a combination product, and if so, which center will lead the review. The FDA is required to respond within 60 days, providing a binding decision.
2. Pre-Request for Designation (Pre-RFD)
   This is a less formal, non-binding method to engage FDA on classification questions. Sponsors can initiate Pre-RFD discussions to explore how the agency views their product, receive preliminary input, and prepare more confidently for the full RFD if needed.Engaging FDA through these channels early in development ensures that sponsors follow the correct regulatory path and gather the appropriate data from the start.

Developing a Regulatory Strategy

After classification is determined, sponsors must design a development strategy that aligns with the assigned pathway.

For drug-led products, this typically involves:

• Filing an Investigational New Drug (IND) application.
• Conducting clinical studies focused on safety and efficacy.
• Submitting a New Drug Application (NDA) or Biologics License Application (BLA).
• Demonstrating that any device component (e.g., injector, delivery system) is safe, functional, and appropriate for the intended user population.

For device-led products, development may involve:

• Submitting a Pre-Submission (Q-Sub) for FDA feedback.
• Filing an Investigational Device Exemption (IDE) if clinical studies are needed.
• Preparing a 510(k), De Novo, or Premarket Approval (PMA) submission.
• Including supporting drug data to ensure safety of the drug component, even if secondary.

Sponsors must also comply with hybrid quality systems, combining drug GMP (21 CFR Parts 210/211) and device QSR (21 CFR Part 820). The FDA has published 21 CFR Part 4 to provide guidance on integrating these systems for combination product development.

Recent Regulatory Updates (2023–2025)

In the past few years, FDA has introduced several new guidances that significantly impact combination product development:

• Combination Product User Fees (2024): Clarifies which user fees apply when submitting a single combined application for a combination product.
• Use-Related Risk Analysis (2024, Draft): Encourages risk assessments tied to user interaction—especially important for auto-injectors and at-home devices.
• Human Factors Engineering (2023): Offers a Q&A-style guide for incorporating usability studies in combination product submissions.
• Drug-Device Software (2023, Draft): Discusses regulatory expectations for mobile apps, sensors, and digital interfaces that form part of a combination product.
• Premarket Pathways for Combination Products (2022): Affirms that most combination products can follow a single submission path, and outlines principles for determining when more than one submission may be needed.

Each of these documents provides valuable insight into FDA expectations, helping sponsors avoid roadblocks and design programs that meet current regulatory standards.

Key Takeaways for Developers in 2025

Combination product development is a multidisciplinary challenge, requiring strategic foresight and active regulatory engagement. Here are four key takeaways for sponsors:

• Start with clear classification: Use 21 CFR 3.2(e) and, when in doubt, engage the FDA early via Pre-RFD or RFD.
• Build your development strategy based on PMOA: Whether your product is drug-led or device-led, understand how that affects submission type, testing, and timelines.
• Address both components: Ensure your development plan includes appropriate testing for both drug and device aspects—neither can be neglected.
• Stay current with FDA guidance: Regulatory expectations are evolving. Human factors, software integration, and use-risk analysis are now central considerations in many combination product reviews.

With a proactive and informed approach, sponsors can reduce regulatory uncertainty, improve submission quality, and bring combination therapies to patients faster.

Celegence offers comprehensive regulatory consulting services tailored for combination products, providing strategic guidance on classification, regulatory submissions, and compliance with both drug and device regulations. Their expert guidance helps streamline development processes, mitigate risks, and facilitate timely market entry for complex combination therapies.

Clinical Evaluation Reports (CERs) are often associated with EU MDR, but an increasing number of manufacturers are now integrating CERs into their FDA submissions, particularly for devices requiring robust clinical evidence. This approach allows manufacturers to present a clear, comprehensive clinical evidence package, ensuring alignment with FDA expectations and reducing review timelines.

CERs in the Context of FDA Submissions

Unlike the EU MDR, the FDA does not mandate a standalone CER as part of a 510(k) or PMA submission. However, substantiating safety and performance of a device through clinical data is a fundamental expectation of the FDA. Clinical evidence plays a pivotal role in FDA review, especially for:

• Novel devices without predicates
• De novo applications
• Devices with high-risk profile
• PMA supplements requiring new safety data

What to Watch For: Common Pitfalls

1. Inadequate Clinical Data
   An unsystematic literature review may result in inclusion of irrelevant or inadequately appraised clinical data, or poorly analyzed data. Additionally, relying on EU-based data without appropriate consideration of its relevance to the U.S. clinical context can further weaken the submission.
2. Lack of Understanding of Submission Types
   Submitting the wrong type of application may lead to significant delays or rejection. Failing to understand the specific requirements associated with the chosen submission type can lead to missing critical information.
3. Unsubstantiated Clinical Claims
   If the clinical data does not directly support the intended use or labelling of the device, it may lead to questions from the reviewer or delays. Each safety and performance claim should be clearly substantiated with traceable evidence.
4. Underutilization of Real-World Evidence (RWE)
   Adverse event trends, registry data, and post-market studies provide real-world evidence that can further enhance the risk-benefit assessments. Not leveraging this data is a missed opportunity to strengthen the submission.
5. Lack of integration across submission sections
   Lack of alignment between clinical, risk, and labeling sections can make it difficult for reviewers to interpret the submission. Maintaining consistency across all sections is essential.

Considerations for a CER aimed at FDA Review

Although CERs are not mandated by FDA, manufacturers should consider the following when drafting a CER to support regulatory submissions:

• Discussion of data relevance, especially for U.S. population
• Clear summary of the clinical evidence, including published literature, registry data, and clinical trials
• Analysis of risks, adverse events, and benefits in alignment with device labeling
• Refer to FDA-recognized standards and guidance, like 21 CFR 814 or the Clinical Evidence Premarket Submission guidance

Useful Tools & Resources

Developing CER content for FDA submissions can be time-consuming, particularly when teams are handling multiple submissions or working under tight timelines. The following tools and data sources can help streamline the process:

• FDA MAUDE Database – for adverse event data and comparator analysis
• ClinicalTrials.gov – to identify relevant ongoing and completed clinical trials
• PubMed and Embase – to identify relevant peer-reviewed clinical literature
• FDA Guidance Documents – to align the CER content with FDA expectations
• FDA CDRH Learn – to stay updated on submission requirements and review trends

These resources are most effective when used strategically, supported by internal alignment and medical writing expertise.

How Celegence Supports CER Preparation for FDA Submissions

Preparing a CER or clinical justification for FDA review isn’t just about data gathering. It’s about crafting a clear, well-structured narrative supported by robust evidence. This is where Celegence adds value.

We combine regulatory expertise with technology to deliver submission-ready CERs, literature reviews, and clinical summaries—on time and in line with FDA expectations.

What sets us apart?

• Clinical writers experienced in FDA and EU submissions
• AI-powered literature reviews and data extraction using CAPTIS®
• Integration of FDA databases and guidance documents into writing workflows
• Quick turnaround times for 510(k), PMA, and De novo pathways
• 99% first-time acceptance rate of clinical documents by regulatory reviewers

Whether you need a literature-based justification, a full CER-style report, or gap analysis of your existing documentation—we offer flexible solutions for every stage of development and submission.

Let’s Work Together

Need help aligning your clinical evidence with FDA expectations? Celegence delivers accurate, regulatory-ready CER support backed by proven expertise and AI tools. Contact our team today to get started.