# Biomedical Engineering - Processes Backlog

## Overview

This document defines the Phase 2 processes backlog for the Biomedical Engineering specialization. These processes cover the key workflows and methodologies used by biomedical engineers in medical device development, tissue engineering, biomechanics, regulatory compliance, and healthcare technology solutions.

## Process Categories

### Medical Device Design and Development

#### 1. Design Control Process Implementation
**Priority:** Critical
**Complexity:** High
**Description:** Implement comprehensive design control processes per FDA 21 CFR 820.30 including user needs capture, design inputs/outputs, verification, validation, design transfer, and design history file management.
**Key Activities:**
- User needs elicitation and documentation
- Design input specification development
- Design output creation and traceability
- Design verification planning and execution
- Design validation with representative users
- Design transfer to manufacturing
- Design history file compilation
**Outputs:** Design control procedures, traceability matrix, design history file

#### 2. Medical Device Risk Management (ISO 14971)
**Priority:** Critical
**Complexity:** High
**Description:** Conduct comprehensive risk management throughout the medical device lifecycle including hazard identification, risk estimation, risk evaluation, risk control, and residual risk assessment.
**Key Activities:**
- Intended use and foreseeable misuse analysis
- Hazard identification and hazardous situation analysis
- Risk estimation (severity and probability)
- Risk evaluation against acceptability criteria
- Risk control measure identification and implementation
- Residual risk evaluation and benefit-risk analysis
- Production and post-production risk monitoring
**Outputs:** Risk management plan, risk analysis report, risk management file

#### 3. Human Factors Engineering and Usability
**Priority:** High
**Complexity:** High
**Description:** Apply human factors engineering principles to ensure medical devices are safe and effective for intended users in intended use environments per IEC 62366-1 and FDA guidance.
**Key Activities:**
- Use-related risk analysis
- User profile and use environment characterization
- Task analysis and critical task identification
- Formative usability evaluation
- User interface design optimization
- Summative usability validation
- Use error analysis and root cause evaluation
**Outputs:** Human factors engineering file, usability validation report

#### 4. Verification and Validation Test Planning
**Priority:** Critical
**Complexity:** Medium
**Description:** Develop comprehensive verification and validation test plans ensuring all design requirements are tested with appropriate methods, sample sizes, and acceptance criteria.
**Key Activities:**
- Test requirement derivation from design inputs
- Test method selection and validation
- Sample size determination and statistical planning
- Test protocol development and approval
- Test execution and data collection
- Results analysis and reporting
- Traceability verification
**Outputs:** V&V master plan, test protocols, test reports

#### 5. Design for Manufacturing and Assembly (DFMA)
**Priority:** High
**Complexity:** Medium
**Description:** Optimize medical device designs for efficient, consistent, and reliable manufacturing while maintaining quality and regulatory compliance.
**Key Activities:**
- Manufacturability assessment
- Part count reduction analysis
- Tolerance analysis and stack-up
- Assembly sequence optimization
- Process capability evaluation
- Design for cleaning and sterilization
- Supplier capability assessment
**Outputs:** DFMA analysis report, manufacturing specifications

### Biocompatibility and Materials

#### 6. Biological Evaluation Planning (ISO 10993)
**Priority:** Critical
**Complexity:** High
**Description:** Develop comprehensive biological evaluation plans for medical devices per ISO 10993-1, determining required biocompatibility testing based on device categorization and contact characteristics.
**Key Activities:**
- Device categorization by body contact nature and duration
- Material identification and characterization
- Existing data and equivalence evaluation
- Testing endpoint determination
- Test lab selection and protocol review
- Risk-based gap analysis
- Biological evaluation plan documentation
**Outputs:** Biological evaluation plan, biocompatibility testing matrix

#### 7. Extractables and Leachables Analysis
**Priority:** High
**Complexity:** High
**Description:** Characterize extractable and leachable substances from medical device materials and assess toxicological risk to patients.
**Key Activities:**
- Extraction study design per ISO 10993-12
- Extraction condition selection
- Analytical method development and validation
- Extractables profiling and identification
- Leachables study under clinical use conditions
- Toxicological risk assessment
- Analytical evaluation threshold application
**Outputs:** E&L study protocols, analytical reports, toxicological risk assessment

#### 8. Biomaterial Selection and Characterization
**Priority:** High
**Complexity:** Medium
**Description:** Select and characterize biomaterials for medical device applications ensuring appropriate mechanical, chemical, and biological properties.
**Key Activities:**
- Material requirements specification
- Candidate material identification
- Mechanical property characterization
- Chemical and surface characterization
- Degradation and stability assessment
- Biocompatibility screening
- Supplier qualification
**Outputs:** Material selection report, material specifications

### Biomechanics and Structural Analysis

#### 9. Finite Element Analysis for Medical Devices
**Priority:** High
**Complexity:** High
**Description:** Conduct finite element analysis to evaluate structural performance, stress distribution, and fatigue life of medical devices, particularly implants and load-bearing devices.
**Key Activities:**
- Geometry creation/import and mesh generation
- Material model selection and validation
- Boundary condition and loading definition
- Mesh convergence studies
- Stress and strain analysis
- Fatigue life prediction
- Model validation against bench testing
**Outputs:** FEA reports, model validation documentation

#### 10. Orthopedic Implant Biomechanical Testing
**Priority:** High
**Complexity:** High
**Description:** Conduct standardized biomechanical testing of orthopedic implants per ASTM and ISO standards including fatigue, wear, and mechanical characterization.
**Key Activities:**
- Test standard identification (ASTM F1717, F2033, ISO 7206)
- Test fixture design and validation
- Sample preparation and measurement
- Static mechanical testing
- Dynamic fatigue testing
- Wear testing protocols
- Data analysis and reporting
**Outputs:** Biomechanical test protocols, test reports

#### 11. Gait Analysis and Musculoskeletal Modeling
**Priority:** Medium
**Complexity:** High
**Description:** Conduct gait analysis and develop musculoskeletal models to evaluate prosthetics, orthotics, and rehabilitation devices.
**Key Activities:**
- Motion capture data collection
- Ground reaction force measurement
- Marker protocol implementation
- Inverse kinematics and dynamics analysis
- Musculoskeletal model development (OpenSim)
- Muscle force and joint loading estimation
- Clinical outcome correlation
**Outputs:** Gait analysis reports, musculoskeletal model files

### Regulatory Affairs and Quality

#### 12. 510(k) Premarket Submission Preparation
**Priority:** Critical
**Complexity:** High
**Description:** Prepare comprehensive 510(k) premarket notification submissions demonstrating substantial equivalence to predicate devices.
**Key Activities:**
- Predicate device selection and comparison
- Device description and intended use documentation
- Performance testing specification
- Substantial equivalence argument development
- Standards compliance documentation
- Labeling review
- eCopy submission package assembly
**Outputs:** 510(k) submission package, FDA correspondence

#### 13. EU MDR Technical Documentation
**Priority:** Critical
**Complexity:** High
**Description:** Develop technical documentation meeting EU Medical Device Regulation (MDR) 2017/745 requirements for CE marking.
**Key Activities:**
- General Safety and Performance Requirements (GSPR) mapping
- Device description and specification documentation
- Design and manufacturing information compilation
- Risk management file preparation
- Clinical evaluation report development
- Post-market surveillance plan creation
- Summary of Safety and Clinical Performance (SSCP)
**Outputs:** Technical documentation file, Declaration of Conformity

#### 14. Post-Market Surveillance System Implementation
**Priority:** High
**Complexity:** Medium
**Description:** Implement post-market surveillance systems to monitor device safety and performance in the field per FDA and EU MDR requirements.
**Key Activities:**
- Complaint handling system establishment
- Adverse event monitoring and reporting (MDR, MEDWATCH)
- Periodic safety update report (PSUR) development
- Post-market clinical follow-up (PMCF) planning
- Trend analysis and signal detection
- CAPA integration
- Vigilance reporting
**Outputs:** PMS plan, PSUR, PMCF plan

### Medical Device Software

#### 15. Software Development Lifecycle (IEC 62304)
**Priority:** Critical
**Complexity:** High
**Description:** Implement medical device software development lifecycle per IEC 62304 including planning, requirements, design, implementation, verification, and maintenance.
**Key Activities:**
- Software safety classification
- Software development planning
- Software requirements specification
- Software architecture design
- Software detailed design
- Unit implementation and verification
- Integration and system testing
- Software release and maintenance
**Outputs:** Software development plan, software requirements specification, software architecture document

#### 16. Software Verification and Validation
**Priority:** Critical
**Complexity:** High
**Description:** Conduct comprehensive software verification and validation ensuring medical device software meets specified requirements and intended use.
**Key Activities:**
- Verification test planning and protocol development
- Unit test development and execution
- Integration testing
- System testing against requirements
- Validation test planning
- User acceptance testing
- Traceability matrix completion
**Outputs:** Software V&V plan, test protocols, V&V reports

#### 17. AI/ML Medical Device Development
**Priority:** High
**Complexity:** High
**Description:** Develop and validate AI/ML-based medical devices following FDA's AI/ML framework and Good Machine Learning Practice (GMLP) principles.
**Key Activities:**
- Problem formulation and intended use definition
- Training data collection and curation
- Algorithm development and training
- Model performance evaluation
- Bias and fairness assessment
- Clinical validation planning
- Predetermined change control plan development
**Outputs:** Algorithm description document, ML model performance report, PCCP

### Sterilization and Packaging

#### 18. Sterilization Validation
**Priority:** Critical
**Complexity:** High
**Description:** Validate sterilization processes for medical devices ensuring sterility assurance level (SAL) achievement per ISO 11135, 11137, or 17665.
**Key Activities:**
- Sterilization method selection
- Bioburden determination
- Product dose establishment
- Process development and characterization
- Installation qualification (IQ)
- Operational qualification (OQ)
- Performance qualification (PQ)
- Sterility assurance level demonstration
**Outputs:** Sterilization validation protocol, validation report

#### 19. Sterile Barrier System Validation
**Priority:** High
**Complexity:** Medium
**Description:** Validate sterile barrier packaging systems per ISO 11607 ensuring package integrity and sterility maintenance through distribution and storage.
**Key Activities:**
- Packaging material selection and qualification
- Seal strength optimization
- Package integrity testing (bubble leak, dye penetration)
- Accelerated aging studies
- Distribution simulation testing
- Stability protocol development
- Packaging validation documentation
**Outputs:** Packaging validation protocol, validation report

### Tissue Engineering and Regenerative Medicine

#### 20. Scaffold Fabrication and Characterization
**Priority:** Medium
**Complexity:** High
**Description:** Design, fabricate, and characterize tissue engineering scaffolds using various techniques including electrospinning, 3D printing, and freeze-drying.
**Key Activities:**
- Scaffold design specification
- Fabrication method selection and optimization
- Pore size and porosity characterization
- Mechanical property testing
- Degradation rate evaluation
- Surface characterization
- Biocompatibility assessment
**Outputs:** Scaffold specifications, characterization reports

#### 21. Cell Culture and Tissue Construct Development
**Priority:** Medium
**Complexity:** High
**Description:** Develop tissue constructs through cell seeding, culture, and maturation on scaffolds using bioreactor systems.
**Key Activities:**
- Cell source selection and expansion
- Cell seeding optimization
- Culture condition establishment
- Bioreactor system design and operation
- Mechanical conditioning protocols
- Tissue maturation monitoring
- Construct characterization (histology, mechanical testing)
**Outputs:** Culture protocols, tissue construct specifications

### Medical Imaging

#### 22. Medical Image Processing Algorithm Development
**Priority:** High
**Complexity:** High
**Description:** Develop and validate medical image processing algorithms for segmentation, registration, reconstruction, and analysis.
**Key Activities:**
- Algorithm specification and design
- Training data preparation (if ML-based)
- Algorithm implementation
- Performance metric definition
- Validation dataset curation
- Algorithm verification and validation
- Clinical utility assessment
**Outputs:** Algorithm design document, validation report

#### 23. DICOM Integration and Interoperability
**Priority:** Medium
**Complexity:** Medium
**Description:** Implement DICOM compliance and healthcare interoperability for medical imaging systems and software.
**Key Activities:**
- DICOM conformance statement development
- Service class implementation (Storage, Query/Retrieve, Worklist)
- PACS integration testing
- IHE profile implementation
- HL7/FHIR integration
- Interoperability testing
- Cybersecurity assessment
**Outputs:** DICOM conformance statement, integration test reports

### Clinical Evidence

#### 24. Clinical Evaluation Report Development
**Priority:** Critical
**Complexity:** High
**Description:** Develop clinical evaluation reports demonstrating clinical safety and performance of medical devices per MEDDEV 2.7/1 and EU MDR requirements.
**Key Activities:**
- Clinical evaluation plan development
- Literature search and review
- Clinical data appraisal
- Equivalent device analysis
- Clinical data synthesis
- Benefit-risk analysis
- Clinical evaluation report writing
- PMCF plan development
**Outputs:** Clinical evaluation plan, clinical evaluation report

#### 25. Clinical Study Design and Execution
**Priority:** High
**Complexity:** High
**Description:** Design and execute clinical studies for medical device approval including IDE studies, pivotal trials, and post-market studies.
**Key Activities:**
- Study objective and endpoint definition
- Study design selection (RCT, single-arm, etc.)
- Sample size calculation
- Protocol development
- IRB/EC submission
- Site selection and initiation
- Data collection and management
- Statistical analysis and reporting
**Outputs:** Clinical protocol, investigator brochure, clinical study report

## Process Priority Matrix

| Priority | Process Count | Categories |
|----------|--------------|------------|
| Critical | 8 | Design Control, Risk Management, V&V, 510(k), MDR, Software Lifecycle, Sterilization, Clinical Evaluation |
| High | 12 | Human Factors, DFMA, Biocompatibility, E&L, FEA, Biomechanical Testing, PMS, Software V&V, AI/ML, Packaging, Image Processing, Clinical Studies |
| Medium | 5 | Biomaterial Selection, Gait Analysis, Scaffold Fabrication, Cell Culture, DICOM Integration |

## Implementation Phases

### Phase 1: Foundation Processes (Critical Priority)
1. Design Control Process Implementation
2. Medical Device Risk Management (ISO 14971)
3. Verification and Validation Test Planning
4. 510(k) Premarket Submission Preparation
5. Software Development Lifecycle (IEC 62304)
6. Sterilization Validation
7. Clinical Evaluation Report Development

### Phase 2: Core Engineering Processes (High Priority)
8. Human Factors Engineering and Usability
9. Biological Evaluation Planning (ISO 10993)
10. Extractables and Leachables Analysis
11. Finite Element Analysis for Medical Devices
12. EU MDR Technical Documentation
13. Post-Market Surveillance System Implementation
14. Software Verification and Validation

### Phase 3: Advanced Applications (High/Medium Priority)
15. AI/ML Medical Device Development
16. Orthopedic Implant Biomechanical Testing
17. Sterile Barrier System Validation
18. Medical Image Processing Algorithm Development
19. Clinical Study Design and Execution
20. Design for Manufacturing and Assembly (DFMA)

### Phase 4: Specialized Processes (Medium Priority)
21. Biomaterial Selection and Characterization
22. Gait Analysis and Musculoskeletal Modeling
23. Scaffold Fabrication and Characterization
24. Cell Culture and Tissue Construct Development
25. DICOM Integration and Interoperability

## Dependencies

```
Design Control Process Implementation
├── Human Factors Engineering and Usability
├── Verification and Validation Test Planning
│   └── Software Verification and Validation
├── Design for Manufacturing and Assembly
└── Medical Device Risk Management
    ├── Biological Evaluation Planning
    │   └── Extractables and Leachables Analysis
    ├── Finite Element Analysis for Medical Devices
    │   └── Orthopedic Implant Biomechanical Testing
    └── Human Factors Engineering and Usability

Software Development Lifecycle
├── Software Verification and Validation
└── AI/ML Medical Device Development

510(k) Premarket Submission
├── Clinical Evaluation Report Development
│   └── Clinical Study Design and Execution
├── Verification and Validation Test Planning
└── Medical Device Risk Management

EU MDR Technical Documentation
├── Clinical Evaluation Report Development
├── Post-Market Surveillance System
└── Medical Device Risk Management

Sterilization Validation
└── Sterile Barrier System Validation
```

## Success Metrics

| Process Category | Key Metrics |
|-----------------|-------------|
| Design Control | Design review completion rate, traceability coverage, design transfer success |
| Risk Management | Hazard identification completeness, risk control effectiveness, residual risk acceptability |
| Regulatory | Submission acceptance rate, review cycle time, deficiency response rate |
| Software | Defect density, test coverage, V&V completion rate |
| Biocompatibility | Testing pass rate, biocompatibility clearance timeline |
| Clinical | Study enrollment rate, endpoint achievement, regulatory acceptance |

## References

- FDA 21 CFR Part 820 - Quality System Regulation
- ISO 13485:2016 - Medical Device Quality Management Systems
- ISO 14971:2019 - Application of Risk Management to Medical Devices
- IEC 62304:2006/AMD1:2015 - Medical Device Software Lifecycle
- IEC 62366-1:2015 - Usability Engineering for Medical Devices
- ISO 10993 Series - Biological Evaluation of Medical Devices
- EU MDR 2017/745 - Medical Device Regulation
- FDA Design Control Guidance for Medical Device Manufacturers
- FDA Guidance on Human Factors and Usability Engineering
