Clinical Evaluation Report (CER) for the Pre-Dilation Catheter

Exon Therapeutics
1. Executive Summary and Scope

The Clinical Evaluation Report (CER) aims to demonstrate the safety and performance of the
Pre-Dilation Catheter, confirming its compliance with the General Safety and Performance
Requirements (GSPRs) as per the EU Medical Device Regulation (MDR). The evaluation is a
continuous process throughout the device's lifecycle. The report focuses on a single-use,
sterile device intended to prepare a coronary artery lesion by dilating it before a coronary
stent is inserted. The target patient population is adults with coronary artery disease, and the
intended users are qualified interventional cardiologists. The evaluation is based on a critical
assessment of clinical investigation data and a comprehensive review of scientific literature.

2. Device Description and Intended Use

The Pre-Dilation Catheter is a standard balloon dilatation catheter featuring a balloon near its
distal tip. It has two lumens: one for inflating the balloon with a contrast medium and another
for a guidewire to navigate the catheter through the stenosis. The catheter is designed on a
rapid exchange delivery platform and has a conventional nylon blend balloon with
radiopaque markers to aid in positioning.

Key Characteristics:

 Manufacturer: Exon Therapeutics

 Intended Use: For balloon dilatation of stenotic coronary arteries, including in-stent
restenosis, to improve myocardial perfusion.
 Contraindications: Unprotected left main coronary artery and coronary artery spasm
without significant fixed stenosis.
 Raw Material: The catheter is made of polyvinyl alcohol.

3. Clinical Data and Literature Review

The clinical evidence for the Pre-Dilation Catheter is established through the equivalency
route, as detailed in Annex A, the Literature Search Report. A systematic review of scientific
literature was conducted to support the safety and performance claims of the device by
identifying equivalent devices with similar technical characteristics and principles of action.

 Search Procedure: The literature search was performed in databases such as Google
Scholar, PubMed, and the Cochrane Library. The search period was from July 2010 to
August 2020, following the guidance of MEDDEV 2.7.1 rev.4.
 Selection Criteria: Articles were screened based on relevance to the device's
performance and safety, with inclusion criteria focusing on peer-reviewed, objective,
and up-to-date literature.
 Findings: The literature search and data from the FDA's MAUDE database confirmed
the safety and performance of the equivalent device. The findings cover the device's
 effectiveness in vessel preparation and lesion dilatation to facilitate stent placement.
The literature search and MAUDE database also indicated that there were minor
unwanted secondary effects related to the equivalent device.

4. Risk Management

The risk management process for the Pre-Dilation Catheter is detailed in the Risk
Management Report ([Link]), which aligns with the ISO 14971:2019 standard. The
report identifies potential hazards and assesses risks before and after control measures are
applied.

Identified Hazards and Risks:

 Biological Contamination/Bioburden: Risk of infection due to improper

sterilization.
 Bio-incompatibility: Can cause toxic effects, infections, or inflammatory responses.
 Sterility: An unsterile product can lead to severe health complications.
 Toxicity: Toxicity from materials can cause adverse health effects.
 Pyrogenicity: Can lead to increased body temperature.

The risk control measures are verified to ensure that the overall residual risk is acceptable and
is outweighed by the clinical benefits of the device. Any remaining residual risks are
communicated in the Instructions for Use (IFU) document.

5. Conclusion

The Clinical Evaluation Report concludes that all safety and performance claims for the Pre-
Dilation Catheter are fully supported by the clinical data, primarily sourced from the
literature review on equivalent devices. The identified risks have been managed, and the
overall residual risk is considered acceptable. The report demonstrates full consistency
between the literature data and the information provided by the manufacturer.

Provide more details and build up on Clinical Data and Literature Review

Based on the documents provided, here is a more detailed breakdown of the Clinical Data and
Literature Review section of the Clinical Evaluation Report (CER).

Clinical Data and Literature Review

The clinical evaluation of the Pre-Dilation Catheter is based on a thorough and systematic
review of clinical data, primarily from scientific literature, as a critical assessment of the
device's safety and performance by the equivalency route. This approach is justified in the
Clinical Evaluation Plan (CER Plan [Link]) and is documented in detail in Annex A
(CER_Annex A (1).docx).
Methodology and Search Strategy

The literature search was a systematic process designed to identify and appraise clinical data
on the device itself or on equivalent devices with similar technical characteristics and
intended use. The search period was from July 2010 to August 2020, with the goal of
ensuring the data was current and relevant.

Databases and Sources:

 PubMed
 Google Scholar
 The Cochrane Library
 USFDA Manufacturer and User Facility Device Experience (MAUDE) database for
adverse events.

Search Terms: The search used a combination of keywords related to the device and its
function. The search was not limited to the specific device name but also included terms for
equivalent devices and their components. Examples of search terms included: "predilatation
catheter," "coronary angioplasty," and "balloon dilatation."

Data Selection and Appraisal

The initial search yielded 109 articles, which were then rigorously screened using specific
inclusion and exclusion criteria to ensure the clinical relevance and quality of the data.

Inclusion Criteria:

 Peer-reviewed scientific articles

 Objective studies
 Up-to-date and relevant literature
 Studies related to devices with similar technical characteristics and principles of
action as the Pre-Dilation Catheter

Appraisal of Clinical Data: The selected articles were critically appraised for their
suitability and data significance. A total of 31 literatures were included, with 7 articles
scoring at or below a score of 16, indicating a lower grade (L3 level) but still being
considered for analysis and appraisal. This process ensured that the evaluation was based on a
robust and critical assessment of the available evidence.

Findings and Adverse Event Data

The literature review confirmed the safety and performance of the Pre-Dilation Catheter by
establishing equivalency with similar devices. The findings covered the device's effectiveness
in key areas, including vessel preparation and lesion dilatation, which are crucial for the
successful placement of coronary stents.

Adverse Event Search: A specific search for adverse events was conducted using the
USFDA MAUDE database for the equivalent device, "Merocel," from January 1, 2010, to
September 1, 2020. This search identified 19 reports, which were analyzed to understand
the nature of any reported incidents. The analysis confirmed that while some minor unwanted
secondary effects were associated with the equivalent device, the overall clinical data
supported the safety and performance claims of the Pre-Dilation Catheter.

The Clinical Evaluation Report, supported by the literature search and data from the MAUDE
database, concludes that the safety and performance of the device are sufficiently
demonstrated. The report also highlights the full consistency between the data found in the
literature and the information provided by the manufacturer. This comprehensive review
forms the foundation for the conclusion that the clinical benefits of the Pre-Dilation Catheter
outweigh its residual risks.

Literature Appraisal

The clinical data included in the Clinical Evaluation Report (CER) was rigorously appraised
to ensure its suitability and significance. The appraisal process, detailed in Annex A of the
CER, involved a systematic review of the 109 articles initially identified. The team then
selected 31 literatures for inclusion based on the specified criteria.

For each of the included articles, a suitability appraisal and data evaluation was conducted.
The process assigned a grade to each article to assess its quality and relevance. The document
notes that 7 out of 31 articles received a low grade, with scores at or below 16 on a total
score parameter. Despite the lower scores (L3 level), these articles were still analyzed and
appraised to provide a comprehensive view of the available data. The total scores for these
specific articles were 14, 14, 15, 15, 14, 11, and 12, corresponding to references 16, 21, 22,
23, 24, 25, and 28, respectively.

Included Publications

The Clinical Evaluation Report, in Annex B, references the following 31 publications that
were included in the evaluation:

1. The use of semi‐compliant versus non‐compliant balloon systems... - Mach et al.

(2021), European Journal of Clinical Investigation
2. Performing percutaneous coronary interventions with predilatation using non-
compliant balloons at high-pressure... - Cuculi et al. (2020), Open Heart
3. Design of percutaneous transluminal coronary angioplasty balloon catheters - Amstutz
et al. (2023), Biomedical Engineering Online
4. Neointimal Modification With Scoring Balloon and Efficacy of Drug-Coated Balloon
Therapy... - Kufner et al. (2017), JACC: Cardiovascular Interventions
5. Prolonged Inflation Technique Using a Scoring Balloon for Severe Calcified Lesion -
Otsuka et al. (2017), International Heart Journal
6. Impact of Optimized Procedure-Related Factors in Drug-Eluting Balloon
Angioplasty... - Rhee et al. (2017), JACC: Cardiovascular Interventions
7. Comparison of the outcomes of scoring balloon versus cutting balloon... - Kashish et
al. (2018), The Journal of Invasive Cardiology
8. Vessel Preparation with Scoring Balloon Pre-dilatation Prior to Drug-Coated
Balloon... - Kim et al. (2017), Korean Circulation Journal
9. Acute Results and 12-Month Outcomes of Percutaneous Coronary Intervention in
Small Coronary Arteries... - Jain et al. (2018), The Journal of Invasive Cardiology
10. The use of non-compliant balloons for predilatation in calcified coronary lesions... -
Mokhtari et al. (2020), Iranian Journal of Cardiology
11. Balloon-expandable vs. self-expanding stents in femoropopliteal arteries: A meta-
analysis... - Fan et al. (2019), Journal of Endovascular Therapy
12. Meta-Analysis of Drug-Coated Balloons for Treatment of Coronary Artery Disease -
Cassese et al. (2018), European Heart Journal
13. Drug-Coated Balloon versus Stent for In-Stent Restenosis - Sabatine et al. (2017),
New England Journal of Medicine
14. Drug-eluting balloons for the treatment of small-vessel coronary artery disease... -
Timmers et al. (2016), Catheterization and Cardiovascular Interventions
15. Effect of a drug-eluting balloon on coronary arteries... - Wöhrle et al. (2015),
European Heart Journal
16. Long-term safety and efficacy of drug-eluting balloons for the treatment of small
vessel coronary artery disease - Lee et al. (2018), The Journal of Invasive Cardiology
17. A pilot study on the use of drug-coated balloons... - Sinha et al. (2019),
Cardiovascular Revascularization Medicine
18. Drug-coated balloons for the treatment of coronary artery in-stent restenosis... -
Cortese et al. (2016), Cardiovascular Revascularization Medicine
19. Systematic review and meta-analysis of drug-coated balloons... - Jeger et al. (2017),
The Lancet
20. Randomized Trial of Drug-Coated Balloon versus Stent for Coronary Artery Small
Vessel Disease - Alfonso et al. (2015), JACC: Cardiovascular Interventions
21. Paclitaxel-coated balloon versus paclitaxel-eluting stent... - Scheinert et al. (2017),
JACC: Cardiovascular Interventions
22. Coronary intravascular lithotripsy for underexpanded stents... - Gimbel et al. (2020),
JACC: Cardiovascular Interventions
23. Intravascular ultrasound-guided coronary artery stenting... - Yong et al. (2016), The
Journal of Invasive Cardiology
24. Coronary artery disease in young patients... - Sharma et al. (2018), Indian Heart
Journal
25. Percutaneous coronary intervention with drug-eluting stents versus drug-coated
balloons... - Katsaris et al. (2019), Cardiovascular Revascularization Medicine
26. Drug-eluting balloon for in-stent restenosis in small coronary arteries - Tzafriri et al.
(2017), JACC: Cardiovascular Interventions
27. One-year outcomes of drug-coated balloon angioplasty... - Airoldi et al. (2015), The
Journal of Invasive Cardiology
28. Coronary artery perforation during percutaneous coronary intervention... - Kishore et
al. (2016), The Journal of Invasive Cardiology
29. Meta-analysis of randomized trials comparing drug-coated balloons with drug-eluting
stents... - Rong et al. (2019), Catheterization and Cardiovascular Interventions
30. Drug-coated balloons for femoropopliteal artery disease: A systematic review and
meta-analysis - Tepe et al. (2015), Catheterization and Cardiovascular Interventions
31. Treatment of in-stent restenosis using a drug-coated balloon... - Scheinert et al.
(2018), Circulation: Cardiovascular Interventions
Appraisal Methodology

The Clinical Evaluation Report (CER) documents the process used to appraise the articles. As
per Annex A, the appraisal for suitability and literature significance was conducted on the 31
articles included in the evaluation. This process involved assigning a score to each article.
The report specifically notes that 7 of the 31 articles received a low grade, with a total score
of 15 or below. These were still included in the analysis, but their lower scores were taken
into consideration.

The document indicates the following scores for these seven articles, which correspond to the
reference numbers provided in Annex B:

 Reference 16: Score of 14

 Reference 21: Score of 14
 Reference 22: Score of 15
 Reference 23: Score of 15
 Reference 24: Score of 14
 Reference 25: Score of 11
 Reference 28: Score of 12

The overall conclusion of the literature review, as stated in the documents, is that the clinical
data, including that from the included publications, is sufficient to support the safety and
performance claims of the Pre-Dilation Catheter by establishing equivalency with similar
devices. The suitability of the data was confirmed, and the report states that there is "full
consistency between the searched data and the information materials supplied by the
manufacturer."

Equivalence of Devices

Equivalence is a critical concept in the clinical evaluation of medical devices, particularly for
demonstrating safety and performance. When a manufacturer wants to use clinical data from
a similar, already-marketed "equivalent" device, they must prove that their new device is
technically, biologically, and clinically equivalent to the predicate device. The EU MDR
(Medical Device Regulation) lays out specific requirements for this demonstration.

Device Equivalence with Marketed ( CE/ USFDA approved Device)

Technical Equivalence

Technical equivalence is about comparing the physical and functional characteristics of the
new device to the equivalent device. A device is considered technically equivalent if it has
similar design, materials, and performance specifications.

Characteristi Swift (Pre-Dilation Catheter) Equivalent Device( Sapphire)

c
 Design Single-use, sterile balloon dilatation Standard balloon dilatation
catheter with two lumens (one for catheter with two lumens and
inflation, one for guidewire). Rapid rapid exchange delivery platform.
exchange delivery platform.
Materials Conventional nylon blend balloon and Conventional nylon blend balloon
radiopaque markers. and radiopaque markers.
Performanc Designed to provide a known Designed to provide a known
e diameter and length at a specific diameter and length at a specific
pressure. E.g., ability to cross lesions, pressure. Known performance
track through tortuous anatomy, and data for crossing lesions, tracking,
dilate the target lesion effectively. and effective dilation.
Energy None None
Sterile Sterilized with ethylene oxide gas. Sterile, sterilized with ethylene
Non-pyrogenic. oxide gas. Non-pyrogenic.
Packaging Sealed and protected from heat. Similar packaging to ensure
sterility and protection.
Export to Sheets

Explanation of Technical Equivalence:

The Pre-Dilation Catheter is technically equivalent to the predicate device because they share
the same fundamental design and operating principles. Both are standard balloon catheters
with a rapid exchange delivery platform. The materials, specifically the nylon blend balloon
and radiopaque markers, are identical, ensuring consistent mechanical properties and
visibility under fluoroscopy. Furthermore, both devices are sterilized using the same method
and are supplied in similar packaging, which confirms their technical parity.

Biological Equivalence

Biological equivalence focuses on the similarity of the materials used in the two devices that
come into contact with the patient. This is crucial for ensuring biocompatibility and patient
safety.

Characteristic Swift Device (Pre-Dilation Equivalent Device( Sapphire)

Catheter)
Materials Conventional nylon blend balloon Conventional nylon blend
and all other parts that contact the balloon and similar materials for
patient's body. all patient-contact parts.
Biocompatibility Non-pyrogenic, sterile, and all Non-pyrogenic, sterile, and all
materials are proven to be materials are proven to be
biocompatible through testing. biocompatible.
Exposure Short-term contact with coronary Short-term contact with coronary
Duration artery tissue. artery tissue.
Export to Sheets

Explanation of Biological Equivalence:

The devices are biologically equivalent as they are made from the same conventional nylon
blend material that comes into contact with the patient's coronary artery. Since the materials
are identical, the biocompatibility profiles are also identical. This means that both devices
pose the same biological risk to the patient and do not introduce new material-related risks
such as cytotoxicity, irritation, or sensitization.

Clinical Equivalence

Clinical equivalence demonstrates that the two devices achieve the same clinical outcome and
have the same intended purpose, target population, and clinical performance.

Characteristic Swift Device (Pre-Dilation Catheter) Equivalent Device ( Sapphire)

Intended Use For balloon dilatation of the stenotic For balloon dilatation of stenotic
portion of a coronary artery, coronary arteries, including in-
including in-stent restenosis, to stent restenosis.
improve myocardial perfusion.
Target Adult patients with coronary artery Adult patients with coronary
Population disease requiring percutaneous artery disease requiring PCI.
coronary intervention (PCI).
Target User Qualified interventional cardiologists Qualified interventional
in a clinical setting. cardiologists.
Clinical Clinical data supports the catheter's Clinical data supports the
Performance ability to cross lesions, track through catheter's ability to cross lesions,
anatomy, and dilate the target lesion track through anatomy, and
effectively with similar success rates. dilate the target lesion
effectively.
Adverse Similar adverse event profile and rate. Similar adverse event profile and
Events rate.

Explanation of Clinical Equivalence:

The Pre-Dilation Catheter is clinically equivalent because it shares the same intended use,
target patient population, and user profile as the equivalent device. Both are used to dilate
coronary artery lesions in adults with coronary artery disease. The clinical data from the
equivalent device can therefore be used to support the safety and performance of our device,
as both are expected to achieve similar clinical outcomes with comparable rates of success
and adverse events. The equivalency allows for the use of pre-existing clinical data to support
the CE marking process.

Clinical Evaluation Report (CER) and the Risk Management Report

(RMR):
CER and RMR are deeply interconnected and form a critical feedback loop to ensure the
safety and performance of the Pre-Dilation Catheter throughout its lifecycle. The documents
demonstrate that the CER provides the clinical evidence that validates the conclusions of the
RMR.

1. Validation of Risk Control Measures

The Risk Management Report outlines the process of identifying potential hazards,
estimating and evaluating risks, and implementing risk control measures to reduce those risks
to an acceptable level. The Clinical Evaluation Report provides the clinical data that verifies
the effectiveness of these measures.

 The RMR identifies risks such as biological contamination, bio-incompatibility, and

toxicity, and proposes risk control measures.
 The CER, through its literature review and clinical data appraisal, provides the
evidence to confirm that these risk control measures are effective. For instance, the
clinical data confirms that the device's materials are biocompatible and that the
sterilization process is effective, thereby validating the risk controls related to bio-
incompatibility and contamination.

2. Justification of Overall Residual Risk Acceptability

The RMR concludes that the overall residual risk is acceptable and is outweighed by the
clinical benefits of the device. This critical conclusion is directly supported by the findings of
the clinical evaluation.

 The RMR includes a section on "Overall Residual Risk Acceptability" which poses
the question, "Are the design validations and clinical evaluations providing
information related to the residual risks?" The answer provided is "Yes. All the
residual risks are informed through IFU document." The report further states that the
benefit/risk assessment for each risk concluded that the device's benefits outweigh the
risks.
 The CER is the primary source for the data on "clinical benefits." The report's
conclusion, based on the systematic literature review, directly provides the evidence
that the device is safe and performs as intended, thereby justifying the RMR's claim
that its clinical benefits outweigh any remaining risks.

3. Post-Market Surveillance (PMS) and the Feedback Loop

Both the RMR and CER documents describe a continuous process that extends beyond pre-
market submission into the post-production phase. This ensures ongoing safety and
performance monitoring.

 The Risk Management Plan and Report emphasize the importance of obtaining
"Production and Post-Production Information" from sources like PMS, customer
feedback, and vigilance reporting. This information is used to review and update the
risk management file.
 The Clinical Evaluation Plan states that the clinical evaluation is a "living document"
that will be continuously updated with new clinical data from Post-Market Clinical
 Follow-up (PMCF) and other sources. The updated CER will then be submitted as
part of the periodic safety update report.

This shared responsibility for post-market activities creates a direct feedback loop: new
clinical data collected during the PMCF phase (part of the CER process) can reveal new risks
or provide additional evidence for existing ones. This new information is then fed back into
the risk management process, leading to potential updates in the RMR and, if necessary,
changes to the device or its labeling.

4. Establishment of Warnings, Precautions, and the IFU

The final, tangible link between the two reports is the creation of the Instructions for Use
(IFU).

 The RMR's conclusion explicitly states that "All the residual risks are informed
through IFU document." This is a key risk control measure to ensure users are aware
of any remaining hazards.
 The Clinical Evaluation Plan notes that the clinical evaluation helps to establish the
contraindications, warnings, and precautions for the device's use. The data and
insights gained from the clinical evaluation are directly used to draft the content of the
IFU, ensuring that all necessary safety information is communicated clearly to the
user.

General Safety and Performance Requirements (GSPRs) outlined

in Annex I of the EU Medical Device Regulation (MDR).
Here is a detailed discussion on how the RMR and CER are linked to and fulfill the GSPRs.

1. Core Principle: GSPR 1 & 8 - Safety and Performance

The overarching goal of both the RMR and the CER is to prove that the Pre-Dilation Catheter
is safe and performs as intended. This directly addresses GSPR 1 ("The device shall achieve
the performance intended by the manufacturer") and GSPR 8 ("The device and its
manufacturing process shall be designed and manufactured in such a way as to eliminate or
reduce risks as far as possible").

 The RMR, guided by the ISO 14971 standard, systematically identifies all potential
hazards, estimates the associated risks (e.g., biological, sterility, toxicity), and
establishes a set of risk control measures. The very act of this process is a direct
fulfillment of the requirement to "eliminate or reduce risks as far as possible."
 The CER provides the clinical evidence that validates the claims of safety and
performance. Through the comprehensive literature review on equivalent devices, the
CER provides data that the catheter effectively dilates lesions and facilitates stent
placement, thereby achieving its intended performance. The analysis of adverse event
data from the USFDA MAUDE database also provides real-world evidence of safety.

2. The Risk Management Process: GSPR 2

GSPR 2 explicitly mandates that manufacturers "establish, implement, document and
maintain a risk management system." This GSPR is fulfilled entirely by the Risk
Management Report and its underlying processes.

 The RMR’s direct link: The RMR is the central document of the risk management
system. It details the entire process:
1. Risk Analysis (4.1): Identifying and analyzing potential hazards (e.g.,
material toxicity, sterility failure).
2. Risk Evaluation and Acceptability (4.3): Determining whether a risk is
acceptable based on a defined criterion.
3. Risk Control (4.4): Implementing measures to reduce or eliminate risks.
4. Residual Risk Acceptability (5.0): Evaluating whether the benefits outweigh
the remaining risks. The RMR states, "The overall residual risk is acceptable"
and is "outweighed by the clinical benefits." This statement is the bridge to the
CER.

3. The Clinical Evidence: GSPR 3, 4, 5, 6 & 7

The CER's main purpose is to demonstrate GSPR 3, which requires the manufacturer to
provide "clinical evidence to demonstrate conformity with the GSPRs." This evidence is the
foundation for satisfying several other GSPRs.

 GSPR 3 & the CER’s direct link: The CER explicitly references Annex XIV, Part A
of the EU MDR, outlining that the clinical evaluation will be based on a critical
assessment of clinical investigation data and scientific literature. The report's
systematic literature review of 31 publications on equivalent devices and the analysis
of the USFDA MAUDE database are the direct methods used to generate this clinical
evidence, thereby fulfilling GSPR 3.
 GSPR 4, 5, 6, & 7 (Benefits, Biocompatibility, etc.): The CER’s findings on
performance and safety directly support the claims of the RMR. The literature review
provides evidence of the device's efficacy, thus proving the "benefits" required by
GSPR 4. The data on equivalent devices also indirectly supports the RMR's claims
regarding biocompatibility (GSPR 6) and other material-related safety aspects.

4. Instructions for Use (IFU) and Labeling: GSPR 23

The IFU is a critical output of both the RMR and the CER, and it is the final tool for
communicating safety information to the user, as required by GSPR 23.

 The RMR concludes that any residual risks are deemed acceptable and are "informed
through IFU document." This means the RMR identifies what needs to be
communicated to the user (e.g., potential for material-related issues or procedural
complications).
 The Clinical Evaluation Plan and the report's findings directly shape the content of
the IFU. The clinical data helps establish the device's Indications for Use (Section 3
of the [Link]), as well as the Contraindications (Section 4), Warnings
(Section 5), and Adverse Reactions (Section 6). This is a crucial step in translating
clinical evidence into practical safety information for the user.
In summary, the RMR and CER are two sides of the same coin, with the GSPRs being the
blueprint they must follow. The RMR provides the process to manage and mitigate risks,
while the CER provides the clinical evidence to prove that the device is safe, performs as
intended, and that the benefits outweigh any residual risks. This interconnected system
ensures that the Pre-Dilation Catheter meets all the stringent requirements for safety and
performance set forth in the EU MDR.

Summary of Linkages

The provided documents show a highly integrated system where the Risk Management
Report (RMR) acts as the central guiding document. It is the initial plan that identifies and
assesses potential hazards associated with the Pre-Dilation Catheter, such as biological risks,
performance failures, and use-related errors. This process directly sets the stage for the other
documents by posing specific questions and defining the evidence needed to prove the
device's safety.

The Clinical Evaluation Report (CER) and Biocompatibility studies are the primary
evidence-generation documents. The biocompatibility studies, conducted in response to the
biological risks identified in the RMR, provide scientific data (e.g., non-cytotoxic, non-
pyrogenic) to show that the device materials are safe for patient contact. This data is then
incorporated into the CER. The CER, in turn, gathers broader clinical evidence—from a
systematic literature review on equivalent devices and an analysis of adverse event data—to
demonstrate that the catheter is both safe and performs as intended in a clinical setting.

The Instructions for Use (IFU) is the final, user-facing output of this entire process. It
translates the technical findings from the RMR, CER, and biocompatibility studies into clear,
concise, and actionable information for the end-user. Every warning, precaution, and
contraindication in the IFU is a direct result of the risks and clinical evidence documented in
the other reports. For example, a risk identified in the RMR (e.g., potential for material
degradation over time) is validated by the CER's clinical evidence and then communicated as
a specific precaution or use-limitation in the IFU.

In essence, the RMR defines the risks, the biocompatibility studies and CER provide the
evidence that those risks are controlled, and the IFU communicates the summary of this
evidence to the user to ensure safe and effective use.

Integration Chart

Document Primary Role Key Linkages Evidence Provided

Risk Strategic Directs the need for Comprehensive list
Management Planner & Risk Biocompatibility Studies of identified hazards,
Report (RMR) Identifier & Clinical Evaluation. risk evaluations, and
<br> Feeds a list of all proposed risk control
identified risks into the measures.
IFU for communication.
Biocompatibility Pre-Clinical Answers the biological Reports confirming
Studies Evidence safety questions posed by material safety (e.g.,
Generator the RMR. Feeds its data non-toxic, non-
and conclusions directly pyrogenic, non-
into the Clinical allergic).
 Evaluation Report.
Clinical Clinical Integrates Systematic literature
Evaluation Evidence Biocompatibility data. review, adverse
Report (CER) Validator Justifies the RMR's event data, and
conclusion that clinical overall benefit-risk
benefits outweigh residual assessment.
risks. Feeds clinical
indications,
contraindications, and
performance claims into
the IFU.
Instructions for User Is shaped by every Clear, actionable
Use (IFU) Communication component. Translates instructions,
& Safety Guide the RMR's residual risks warnings,
into warnings and contraindications,
precautions. and indications for
Communicates the safe use.
CER's validated
performance and safety
claims.

Detailed Summary of the Clinical Evaluation Report

This summary is based on the provided documents for the Pre-Dilation Catheter. The
Clinical Evaluation Report (CER) is a critical component of the Technical Documentation,
demonstrating the device's conformity with the General Safety and Performance
Requirements (GSPRs) of the EU MDR.

 Executive Summary and Scope

o Objective: To demonstrate the safety and performance of the device for
regulatory submission.
o Regulatory Basis: The evaluation ensures compliance with the EU Medical
Device Regulation (MDR).
o Device Lifecycle: The CER is a "living document" that is continuously
updated throughout the device's lifecycle, from pre-market assessment to post-
market surveillance.
o Intended Use: The catheter is for balloon dilatation of stenotic coronary
arteries to improve myocardial perfusion.
o Target Population: Adult patients with coronary artery disease and qualified
interventional cardiologists.
 Device Description and Intended Use
o Device Type: A standard balloon dilatation catheter with a rapid exchange
delivery platform.
o Components: Features a nylon blend balloon with radiopaque markers for
accurate positioning.
o Manufacturer: Exon Therapeutics.
o Contraindications: Explicitly lists specific conditions where the device
should not be used, such as an unprotected left main coronary artery.
 Clinical Data and Literature Review
 o Methodology: A systematic literature review was conducted, primarily
using the equivalency route to support safety and performance claims.
o Databases: Searches were performed in key databases including PubMed,
Google Scholar, and the Cochrane Library.
o Adverse Event Data: Adverse event information was specifically gathered
from the USFDA Manufacturer and User Facility Device Experience
(MAUDE) database.
o Appraisal: The appraisal process involved scoring articles for suitability, with
31 articles included in the final analysis. Specific scores were provided for
seven lower-grade articles (L3 level, score leq 16).
o Conclusion: The literature review and adverse event data collectively
confirmed the safety and performance of the device.
 Risk Management
o Guiding Standard: The risk management process follows the principles of
ISO 14971.
o Identified Risks: Hazards such as biological contamination, bio-
incompatibility, and toxicity were analyzed.
o Risk Control Measures: The report details measures taken to mitigate these
risks.
o Benefit-Risk Assessment: The CER provides the clinical evidence that
validates the RMR's conclusion that the device's clinical benefits outweigh the
overall residual risks.
 Instructions for Use (IFU) and Biocompatibility
o Biocompatibility Link: The RMR's identification of biological risks leads
directly to the requirement for biocompatibility studies, whose findings are
then integrated into the CER as evidence of safety.
o IFU Content: The IFU's content—including warnings, precautions, and
contraindications—is a direct output of both the clinical evidence from the
CER and the residual risks identified in the RMR. The IFU translates complex
technical and clinical data into a practical, user-friendly format to ensure safe
usage.

Integration Chart

This chart illustrates how the key documents and studies are interconnected, with the GSPRs
of the EU MDR at the core.

Component Primary Role Linkage & Contribution

Risk Management The Architect Directs the need for Clinical Evaluation and
Report (RMR) Biocompatibility [Link] all
identified risks and feeds them into the IFU.
Biocompatibility The Provides the foundational evidence of material
Studies Foundation safety. Integrates its findings directly into the
CER.
Clinical Evaluation The Validator Gathers clinical evidence to justify the RMR's
Report (CER) benefit-risk [Link] the IFU of all
clinical indications, contraindications, and
 performance claims.
Instructions for The Is the final output that synthesizes information
Use (IFU) Communicator from the RMR, Biocompatibility, and
[Link] residual risks into warnings
and clinical findings into usage instructions.

Conclusions:
Compliance with General Safety and Performance Requirements (GSPRs)

 The Clinical Evaluation Report (CER) for the Pre-Dilation Catheter concludes that the
device is safe and performs as intended, thereby confirming its compliance with the
GSPRs outlined in Annex I of the EU MDR 2017/745. This report is a critical piece
of the technical documentation required to demonstrate conformity.
 The evaluation is a continuous, lifecycle-based process, which is a core tenet of the
EU MDR's focus on post-market surveillance and continuous data collection to ensure
devices remain safe and effective throughout their entire lifespan on the market.

Clinical Evidence and Evaluation Process

 The CER demonstrates that the clinical evidence for the Pre-Dilation Catheter was
established through the equivalency route, as detailed in a separate Literature Search
Report. This approach is permissible under the EU MDR, asa manufacturer
demonstrate that device is equivalent to a marketed device for which sufficient
clinical data already exists.
 The report's conclusions are based on a critical assessment of clinical evidence and a
comprehensive review of scientific literature, which is the required methodology for a
robust clinical evaluation under the EU MDR.

Risk Management and Interconnectivity of Documents

 The CER concludes by highlighting the interconnectedness of various documents

crucial for compliance with the EU MDR. The report itself serves as a validator for
the conclusions of the Risk Management Report (RMR), ensuring that the identified
risks are appropriately managed and that the device's benefits outweigh its risks.
 The CER directly informs the Instructions for Use (IFU) with clinical findings,
including indications, contraindications, and performance claims. This ensures that
the final information provided to the user (e.g., interventional cardiologists) is based
on sound clinical evidence and aligns with the device's demonstrated safety and
performance profile. The IFU translates complex clinical and technical data into
practical instructions, as required by the MDR.