A comprehensive comparison table that details the differences between Medical Devices, In Vitro Diagnostics (IVDs),

Combination Products, and Pharmaceuticals,

In Vitro Diagnostics
Aspect Medical Devices Combination Products Pharmaceuticals
(IVDs)
Instruments or apparatus
intended for medical
Reagents, instruments,
purposes to diagnose, Products that combine a drug (or Chemical substances used
or systems designed to
prevent, monitor, or treat biologic) and a medical device, or to treat, cure, prevent, or
perform tests on
diseases, achieving their a device and a biological diagnose diseases by
Definition specimens from the
primary intended purposes product, intended for use interacting with biological
human body for the
through physical or together to achieve specific systems through chemical
purpose of diagnosing
mechanical means rather therapeutic or diagnostic effects. or biological mechanisms.
diseases or conditions.
than through chemical
action.
- Surgical instruments - Antibiotics (e.g.,
(scalpels, forceps) amoxicillin)
- Blood glucose meters - Drug-eluting stents
- Diagnostic imaging devices - Vaccines (e.g., influenza
- Pregnancy test kits - Prefilled syringes (e.g., with
(MRI, ultrasound) vaccine)
- PCR kits for infectious vaccines)
- Therapeutic devices - Antidepressants (e.g.,
Examples diseases - Insulin pumps that deliver
(pacemakers, insulin pumps) fluoxetine)
- Blood typing reagents medication
- Dental devices (crowns, - Analgesics (e.g.,
- HIV and COVID-19 - Transdermal patches (e.g.,
braces) ibuprofen)
tests nicotine patches)
- Wound care products - Chemotherapeutic agents
(bandages, sutures) (e.g., cisplatin)
- Physical Mechanism: - Biochemical - Dual Mechanism: Combines - Pharmacological Action:
Utilizes physical forces to Reactions: Detects and the mechanisms of both the Interacts with biological
achieve results (e.g., stents measures specific drug and device; for example, a systems at the molecular
open blocked arteries). biomarkers through drug-eluting stent releases level to elicit a therapeutic
- Electrical Mechanism: antigen-antibody medication to prevent artery re- effect (e.g., antibiotics
Mechanism of Uses electrical impulses (e.g., interactions (e.g., narrowing while providing disrupt bacterial cell walls).
Action pacemakers regulate heart pregnancy tests). mechanical support. - Physiological
rhythms). - Molecular - Therapeutic and Diagnostic: Modulation: Alters
- Combination of Both: Techniques: Provides both treatment and physiological processes
Some devices may have both Techniques such as PCR monitoring functions (e.g., antidepressants
mechanisms (e.g., an insulin amplify DNA for simultaneously (e.g., an insulin adjust neurotransmitter
pump that delivers insulin pathogen detection (e.g., pump delivering insulin based levels in the brain).
 In Vitro Diagnostics
Aspect Medical Devices Combination Products Pharmaceuticals
(IVDs)
based on blood glucose COVID-19 tests). on continuous glucose - Targeted Action: Many
levels). - Microbial Culturing: monitoring). drugs are designed to target
Cultures pathogens specific receptors or
from samples for biological pathways (e.g.,
identification (e.g., blood monoclonal antibodies
cultures). targeting cancer cells).
- Risk Classification:
IVDs are also classified - Approval Process:
by risk; low, moderate, Requires submission of an
- Classification: Devices are
or high-risk - Combination Product Investigational New Drug
classified into Class I (low
classifications affect the Regulations: Governed by both Application (IND) before
risk), Class II (moderate
regulatory pathway (e.g., drug and device regulations; clinical trials and a New
risk), and Class III (high risk)
CLIA regulations in the must comply with FDA Drug Application (NDA) or
based on their intended use
USA). regulations for combination Biologics License
and potential harm.
- Regulatory Bodies: products (21 CFR Parts 3 and 4). Application (BLA) for
- Regulatory Bodies:
Subject to FDA - Review Processes: May marketing approval.
Regulatory Governed by organizations
oversight with specific undergo a single review process - Phase Trials: Undergo
Pathways like the FDA (USA) and EMA
guidelines for IVDs (21 or separate reviews for each multiple phases of clinical
(EU).
CFR Part 809). component depending on the trials to assess safety,
- Premarket Approval: Class
- Validation product type. dosage, and efficacy (Phase
III devices typically require
Requirements: - Clinical Evidence: Must I, II, III).
extensive clinical data
Requires demonstration provide safety and effectiveness - Post-Marketing
demonstrating safety and
of analytical and clinical evidence for both the device and Surveillance: Ongoing
efficacy; Class I devices may
performance (accuracy, the drug components. monitoring for safety and
need only registration.
precision, reliability) but efficacy, requiring adverse
not necessarily clinical event reporting.
efficacy.
- Clinical Studies: Required - Test Validation: - Clinical Evidence for Both - Robust Clinical Trials:
for higher-risk devices; Requires comprehensive Components: Must demonstrate Must provide substantial
studies assess safety, validation to ensure safety and efficacy for both the evidence through
Clinical efficacy, and performance in analytical performance drug and device; can require randomized controlled trials
Evaluation patients. (sensitivity, specificity) specific clinical trials addressing and observational studies
- Bench Testing: Involves and clinical performance both components. to establish safety and
evaluating device (how well the test - Interdisciplinary Expertise: efficacy.
performance through predicts clinical Requires collaboration among - Endpoints: Clear clinical
 In Vitro Diagnostics
Aspect Medical Devices Combination Products Pharmaceuticals
(IVDs)
laboratory testing prior to outcomes). regulatory, clinical, and endpoints are necessary to
clinical trials. - Regulatory technical experts due to its dual evaluate the drug's effects
Compliance: Clinical nature. on patient outcomes (e.g.,
utility must be survival rates, symptom
established, showing improvement).
that the test provides
useful information for
clinical decision-
making.
- ISO 15189
- Good Manufacturing
- ISO 13485 Compliance: Compliance:
- Integrated Compliance: Must Practices (GMP):
Must adhere to quality Laboratories conducting
comply with quality systems for Compliance with GMP
management systems IVD testing must comply
both devices (ISO 13485) and regulations is mandatory to
specific to medical devices, with standards specific
pharmaceuticals (GMP), ensure drug quality and
Quality ensuring consistent quality to laboratory services to
necessitating a coordinated consistency during
System throughout the ensure quality and
quality management approach. production.
Regulations manufacturing process. reliability.
- Risk Management: - Quality Assurance: Must
- Design Controls: Requires - Quality Control:
Continuous risk assessment and have ongoing quality
stringent controls during Ongoing quality
management strategies are assurance measures
product development and assurance processes to
essential for both components. throughout the drug
manufacturing processes. validate the reliability of
manufacturing process.
test results.
- Post-Market Studies: - Monitoring Both
- Ongoing Monitoring: - Adverse Event
May require post- Components: Continuous
Required to track device Reporting: Must report
market performance monitoring of safety and
performance in real-world serious adverse events and
studies to assess long- effectiveness for both the drug
settings, including adverse conduct post-marketing
term effectiveness and and device components,
event reporting to regulatory studies as mandated by
Post-Market reliability in clinical including post-market studies to
bodies. regulatory authorities.
Surveillance settings. evaluate performance.
- Field Safety Corrective - Risk Management Plans:
- Adverse Event - Risk Management Plans:
Actions: Must implement Required to assess and
Reporting: Mandatory Must have plans in place to
corrective actions if safety or manage risks associated
reporting of incidents address any risks identified
performance issues are with the drug post-
affecting the safety or during post-marketing
identified post-market. approval.
performance of the IVD. surveillance.
 In Vitro Diagnostics
Aspect Medical Devices Combination Products Pharmaceuticals
(IVDs)
- Test Instructions:
Must provide - Detailed Information:
- Clear Instructions: Labels comprehensive - Comprehensive Information: Requires comprehensive
must include indications for instructions on how to Labels must provide detailed labeling that includes
use, contraindications, perform the test, information on both the device indications, dosage,
warnings, and detailed interpret results, and and drug components, including administration routes,
Labeling instructions for safe and understand limitations. indications, dosage, instructions potential side effects, and
Requirements effective use. - Regulatory for use, and contraindications. contraindications.
- User Information: Must be Compliance: Labels - Patient Safety: Information - Patient Education:
presented in a clear, user- must comply with must emphasize safe and Labels must ensure
friendly manner to facilitate specific regulatory effective use of the combined patients understand how to
correct usage. requirements related to product. use the medication safely
specimen handling and and effectively.
storage instructions.
- Focus on Treatment or - Diagnostic Focus: - Therapeutic Focus:
Monitoring: Devices are Primarily intended for - Dual Purpose: Intended for Primarily intended for
intended to support patient the in vitro examination therapeutic and diagnostic treating or preventing
Intended Use care through direct of specimens to provide purposes, facilitating both disease through chemical
therapeutic or diagnostic diagnostic information, treatment and monitoring of interactions with biological
means without interacting aiding in clinical patients, enhancing patient care. systems, targeting specific
chemically with the body. decision-making. conditions or symptoms.
EU Medical Devices Approval Process ├── Conduct clinical trials if necessary
└── Review and approval by Notified Body
[1. Pre-Market Preparation]
├── Identify Device Type and Classification ↓
│ ├── Classify under MDR (Medical Device
Regulation) 2017/745 [3. Clinical Evaluation]
│ └── Determine applicable EU directives ├── Conduct Clinical Studies (if required)
├── Conduct Risk Assessment │ ├── Design and execute studies to assess safety
│ ├── Identify potential hazards and performance
│ └── Evaluate risk management according to ISO │ └── Follow Good Clinical Practice (GCP) guidelines
14971 ├── Prepare Clinical Evaluation Report (CER)
├── Develop Technical Documentation (TD) │ ├── Summarize clinical data and literature
│ ├── Device description and specifications │ └── Analyze risks and benefits
│ ├── Manufacturing processes └── Assess Clinical Data and Risk-Benefit Ratio
│ ├── Design verification and validation └── Ensure data supports device claims
│ └── Performance data and risk analysis ↓
└── Establish Quality Management System (QMS)
├── Implement ISO 13485 standards [4. Technical Documentation Submission]
└── Document procedures for design, production, ├── Submit TD to Notified Body (for Class II and III)
and post-market activities ├── Include Comprehensive Documentation:
↓ │ ├── Risk Management File
│ ├── Labeling and Instructions for Use
[2. Conformity Assessment] │ ├── Design and Manufacturing Information
├── Class I Devices │ └── Clinical Evaluation Report
│ └── Self-Declaration of Conformity └── Ensure Compliance with MDR Requirements
│ ├── Prepare Declaration of Conformity └── Confirm documentation aligns with EU
│ └── Prepare Technical Documentation for records regulations
├── Class IIa Devices ↓
│ └── Involve Notified Body for Assessment [5. Notified Body Assessment]
│ ├── Submit Technical Documentation to Notified ├── Review Technical Documentation
Body │ ├── Evaluate compliance with MDR
│ ├── Review by Notified Body │ └── Verify data integrity and reliability
│ └── Issue Certificate of Conformity if compliant ├── Conduct QMS Audits
├── Class IIb Devices │ ├── On-site inspections of manufacturing facilities
│ └── Similar to Class IIa but with more extensive │ └── Review of quality control processes
documentation ├── Verify Compliance with Standards
└── Class III Devices │ ├── Ensure adherence to relevant harmonized
└── Full Conformity Assessment standards
├── Submit extensive clinical data │ └── Evaluate risk management practices
 └── Issue Certificate of Conformity (if compliant)
└── Document results and provide
recommendations

[6. CE Marking]
├── Affix CE Mark on Medical Device
│ ├── Ensure visibility on device and packaging
│ └── Include identification number of Notified Body
(for Class II and III)
└── Indicate Compliance with EU Regulations
└── Confirm alignment with the applicable
regulations

[7. Post-Market Surveillance]

├── Implement Post-Market Surveillance Plan
│ ├── Monitor device performance and user feedback
│ └── Maintain records of adverse events
├── Monitor Device Performance and Safety
│ ├── Analyze reports and data trends
│ └── Identify areas for improvement or further action
└── Report Adverse Events to Competent
Authorities
└── Notify incidents that affect patient safety

[8. Periodic Safety Update Report (PSUR)]

├── Prepare PSUR for Class IIa, IIb, and III Devices
│ ├── Summarize post-market surveillance findings
│ └── Include analysis of adverse events and risk
assessments
└── Submit PSUR to Regulatory Authorities as
Required
└── Ensure timely submission based on regulatory
timelines
US FDA Approval Process │ └── Assign a review team
[1. **Device Classification**] ├── **Review Documentation**
├── **Determine Device Type** │ ├── Evaluate safety and effectiveness
│ ├── **Class I**: Low risk │ ├── Analyze clinical data (for PMA submissions)
│ ├── **Class II**: Moderate risk │ └── Review labeling and manufacturing
│ └── **Class III**: High risk information
└── **Check for Predicate Device** └── **FDA Decision**
└── Determine if a similar device exists for ├── **510(k) Clearance**:
comparison │ └── If safe and effective, issue clearance letter
└── **PMA Approval**:
↓ └── If meets standards, issue approval order
↓
[2. **Pre-Submission Activities**]
[5. **Post-Approval Activities**]
├── **Request Feedback from FDA**
├── **Manufacturing and Quality Control**
│ ├── Submit **Pre-Submission (Q-submission)**
│ ├── Implement **Good Manufacturing Practices
│ └── Discuss testing requirements and protocols
(GMP)**
└── **Conduct Feasibility Studies (if needed)**
│ └── Maintain **Quality Management System
└── Gather preliminary data on device performance
(QMS)**
↓
├── **Post-Market Surveillance**
│ ├── Monitor device performance and adverse events
[3. **Prepare Regulatory Submission**] │ └── Report adverse events to FDA (**MAUDE**
├── **Choose Submission Type** database)
│ ├── **510(k) Submission** (for Class I and II) └── **Periodic Reporting**
│ └── **PMA (Premarket Approval)** for Class III └── Submit required reports to FDA as per
├── **Compile Required Documentation** regulations
│ ├── Device description ↓
│ ├── Indications for use [6. **Device Modifications (if applicable)**]
│ ├── Labeling information ├── **Assess Impact of Modifications**
│ ├── Performance testing data │ ├── **Minor Modifications**:
│ └── Clinical data (if required) │ │ └── May not require new submission
└── **Submit to FDA** │ └── **Major Modifications**:
└── Complete the submission process through the │ └── May require new **510(k)** or **PMA**
appropriate channels submission
└── **Submit Revised Documentation**
↓ └── Follow appropriate procedures based on
[4. **FDA Review Process**] modification type
├── **FDA Acknowledgement**
│ ├── Confirm receipt of submission