Regulatory Projects
What is Regulatory Compliance?
Regulatory compliance in medical device and drug development means designing, testing, manufacturing, and marketing products in full alignment with government laws, regulations, and quality standards to ensure they are:
• ✅ Safe
• ✅ Effective
• ✅ High quality
• ✅ Traceable
• ✅ Audit-ready
TMEP Consulting has a structured system that governs the entire product lifecycle.
💊 In Drug Development
Regulatory compliance ensures that a drug is scientifically validated, ethically tested, and consistently manufactured.
Key Regulatory Bodies
• U.S. Food and Drug Administration (FDA)
• European Medicines Agency (EMA)
• MHRA (UK), Health Canada, etc.
Key Regulations & Standards
• 21 CFR Parts 210 & 211 (GMP)
• 21 CFR Part 312 (IND)
• ICH E6 (GCP)
• ICH Q8–Q10 (Quality & Risk Management)
• GLP (Good Laboratory Practice)
What Compliance Covers
• Preclinical GLP studies
• IND submission
• Clinical trials (Phase I–III) under GCP
• NDA or BLA submission
• Manufacturing under GMP
• Post-marketing surveillance
If a drug company skips compliance, the product cannot be approved or sold.
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🏥 In Medical Device Development
Regulatory compliance ensures devices are safe, perform as intended, and are manufactured under a controlled Quality Management System.
Key Regulatory Bodies
• U.S. Food and Drug Administration (FDA – CDRH)
• European Medicines Agency (eu regulator”] (EU MDR through Notified Bodies)
• UKCA (UK)
Key Regulations & Standards
• 21 CFR Part 820 (Quality System Regulation)
• ISO 13485
• ISO 14971
• EU MDR 2017/745
• IEC 62304 (software lifecycle)
What Compliance Covers
• Design Controls (DHF)
• Risk Management
• Verification & Validation
• Clinical Evaluation
• 510(k), De Novo, or PMA submissions
• Complaint handling & CAPA
• Post-market surveillance
Without compliance, a device cannot receive clearance or CE marking.
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Regulatory compliance is about:
Building quality into the product from the beginning — not fixing problems at the end.
At TMEP Consulting, when we manage regulatory projects, we connects with all essential departments such as:
• Engineering
• Clinical
• Manufacturing
• Quality
• Documentation
• Risk Management
🎯 Why It Matters:
Non-compliance can lead to:
• FDA Warning Letters
• Product recalls
• Clinical holds
• Market withdrawal
• Legal liability
🔎 In Simple Terms
In medical device and drug development:
Regulatory compliance =
Following the rules while proving with documentation that your product is safe and effective before it reaches patients.
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TMEP Consulting Regulatory Roadmap
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💊 DRUG DEVELOPMENT REGULATORY ROADMAP
(Preclinical → Post-Market) Projects
1️⃣ Regulatory Strategy & Pathway Assessment
• Product classification & jurisdiction mapping (FDA, EMA, MHRA, etc.)
• Regulatory pathway determination:
• IND vs NDA vs BLA
• 505(b)(1), 505(b)(2), ANDA
• Orphan, Fast Track, Breakthrough designation strategy
• Gap analysis & regulatory intelligence
Deliverable: Regulatory Strategy Plan + Global Submission Matrix
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2️⃣ Preclinical & IND Preparation
• Pre-IND meeting support
• Nonclinical study compliance (GLP oversight)
• CMC documentation strategy
• IND module preparation (eCTD format)
• Risk assessment & safety evaluation
Submission:
Investigational New Drug (IND)
3️⃣ Clinical Phase Regulatory Oversight
• Phase I–III submission amendments
• Annual reports & safety reporting
• Protocol amendments
• DSMB coordination
• GCP compliance oversight
• EMA Clinical Trial Application (CTA) support
TMEP Focus: Traceability, inspection readiness, audit defense.
4️⃣ NDA / BLA Submission
• eCTD publishing
• Module 1–5 compilation
• CMC validation alignment
• Integrated Summary of Safety & Efficacy
• Pre-Approval Inspection (PAI) readiness
• Advisory Committee preparation
Submission:
👉 NDA (New Drug Application)
👉 BLA (Biologics License Application)
5️⃣ Post-Marketing & Lifecycle Management
• Labeling updates
• REMS management
• Pharmacovigilance support
• Annual reports
• Global variation filings
• Post-Marketing Surveillance (Phase IV)
🏥 MEDICAL DEVICE REGULATORY ROADMAP
(Concept → Commercialization → Lifecycle)
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1️⃣ Regulatory Classification & Strategy
• Device classification (Class I, II, III)
• Predicate device identification
• Regulatory pathway:
• 510(k)
• De Novo
• PMA
• Global pathway planning (FDA, EU MDR, UKCA)
Deliverable: Regulatory Strategy & Gap Assessment Report
2️⃣ Design Controls & QMS Alignment
• ISO 13485 implementation
• FDA 21 CFR 820 compliance
• Design History File (DHF)
• Risk Management (ISO 14971)
• Design Inputs/Outputs traceability matrix
• Verification & Validation plan
TMEP Specialty: Bridging Agile development with V-Model validation.
3️⃣ Pre-Submission & Regulatory Engagement
• FDA Q-Sub meetings
• Pre-Sub package preparation
• Clinical Evaluation Plan (if required)
• Human Factors Engineering documentation
4️⃣ Submission Preparation
For 510(k):
• Substantial equivalence analysis
• Performance testing documentation
• Software validation documentation
• Cybersecurity documentation
• Biocompatibility & sterilization validation
For PMA:
• Clinical data compilation
• Manufacturing site readiness
• Full technical file preparation
For EU MDR:
• Technical Documentation (Annex II & III)
• Clinical Evaluation Report (CER)
• Post-Market Clinical Follow-Up (PMCF)
• Notified Body coordination
5️⃣ Post-Market Compliance & Surveillance
• CAPA management
• Complaint handling system
• MDR/Vigilance reporting
• Audit readiness & inspection defense
• Change management & new submissions
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🔎 TMEP Regulatory Projects
✔ Regulatory + Quality + Validation integrated
✔ ISO + FDA + EMA alignment
✔ Traceability from concept to commercialization
✔ Audit-ready documentation
✔ eCTD & Technical File publishing support
✔ Global regulatory strategy planning
🌍 Optional Add-On for Your Branding
You manage projects involving:
STRATEGY
SUBMISSION
LIFECYCLE
Gap Analysis
IND / 510(k)
Post-Market
Pre-Sub Meetings
NDA / PMA
Vigilance
Risk Management
EMA Filing
CAPA
Clinical & Regulatory Strategy built around Primary Mode of Action (PMOA) for a combination product with both drug and device components. This is a working roadmap we adapt to product specifics, timelines, and internal resources.
1. Establish PMOA and Regulatory Lead
• Determine PMOA (scientific evidence should show which component provides the single, most important therapeutic action).
• Based on PMOA:
• If drug action is primary → CDER leads review.
• If device action is primary → CDRH leads review.
• Document the PMOA determination with justification (mechanistic data, in vitro/in vivo results, clinical rationale). This is critical for FDA assignment and for internal alignment.
2. FDA Engagement and Regulatory Pathway
• Pre-submission planning:
• Request a pre-submission meeting(s) with FDA (CDER and/or CDRH as appropriate; combination product requests go to the Office of Combination Products (OCP) for assignment guidance).
• Prepare a briefing package covering PMOA rationale, CMC/DHF status, nonclinical and clinical plans, testing strategy, and proposed regulatory pathway.
• Clarify whether submissions should be:
• IND (if drug-led) or IDE (if device-led) for investigational activities, OR
• A combination product review pathway (e.g., NDA with device, PMA with drug, or a BLA or 510(k) as relevant).
• Ask FDA about any specific guidance or expectations for combination products, including requirements for integrated review.
3. IND vs IDE Planning (investigational strategy)
• If CDER leads (drug primary):
• Prepare an IND that includes:
• Clinical protocol(s) for the combination product (including device use and operator training).
• Nonclinical pharmacology/toxicology and device biocompatibility/safety data.
• CMC package for drug substance/product; device description and manufacturing controls summary.
• Risk analysis and mitigation plans.
• Consider requesting a Pre-IND meeting to align on nonclinical and clinical requirements.
• If CDRH leads (device primary):
• Prepare an IDE that includes:
• Device design and testing results sufficient to support clinical use.
• Biocompatibility, sterilization, electrical safety/EMC, software validation (if applicable).
• Clinical protocol(s) addressing safety and performance endpoints; include drug components’ safety data and CMC summary.
• Consider an Early Collaboration or Q-Submission with CDRH to confirm human factors, testing, and clinical endpoints.
• Hybrid/Parallel approach:
• For some combination products you may need both an IND and an IDE, or coordinated interactions—use OCP to clarify.
4. CMC and DHF Alignment (concurrent development and documentation)
• Goal: Produce aligned, cross-referenced CMC and Device Design History File (DHF) documentation to support regulatory submissions and reduce review friction.
• Key actions:
• Create a joint traceability matrix mapping drug critical quality attributes (CQAs), device critical-to-function characteristics, and clinical performance requirements to design inputs, specifications, verification/validation tests, and controls.
• Synchronize change control processes for impacts that cross components (e.g., material changes in device that affect drug stability or delivery).
• Establish integrated supplier qualification and audits covering both drug and device vendors.
• Draft modular submission-ready CMC sections and DHF modules concurrently so each supports the other:
• CMC: drug substance/process, drug product formulation/stability, container/closure interactions with device, analytical methods, batch records.
• DHF: user needs, design inputs/outputs, risk management (ISO 14971), verification/validation reports, manufacturing process control, device labeling and IFU.
• Include interface specifications for drug-device interaction (dose delivery accuracy, flow rates, sealing, shelf life together).
5. Nonclinical and Bench Testing Strategy
• Nonclinical plan to address safety and performance of the integrated system:
• Biocompatibility and toxicology for device materials and any leachables/extractables.
• In vitro bench testing: durability, mechanical performance, dose-delivery accuracy, flow characteristics, software validation, EMC, sterilization validation.
• Stability testing: combined product under intended storage/use conditions; accelerated and real-time stability plans.
• Animal studies if needed: demonstrate safety and relevant functional endpoints of the combination product.
• Follow relevant standards (ISO, ASTM, FDA guidance documents) and cite them in submission.
6. Clinical Strategy
• Design clinical programs to address safety and effectiveness of the combined product under real-world use.
• Align endpoints to PMOA and regulatory expectations from CDER/CDRH:
• Drug-led: primary endpoints focusing on pharmacologic/therapeutic outcomes; device use outcomes as supporting safety/performance data.
• Device-led: primary endpoints on device performance/safety; pharmacologic outcomes as supportive.
• Include human factors/usability engineering study to show safe and effective use by intended users.
• Define key inclusion/exclusion criteria, monitoring, and data collection for device metrics, adverse events, and drug-related safety.
• Plan for interim analyses if appropriate and pathways for expedited programs (e.g., Breakthrough Device Program or expedited drug pathways) if eligible.
7. Quality Systems, Risk Management, and Regulatory Documentation
• Implement integrated quality management:
• Drug: cGMP/compliance for drug manufacturing.
• Device: QMS aligned with 21 CFR 820 and ISO 13485.
• Ensure processes for complaint handling, CAPA, and change control cover the combination product interfaces.
• Risk management:
• Complete ISO 14971 risk analysis for the device and include drug-device interface hazards.
• Link risk controls to verification/validation and clinical mitigations.
• Documentation packages to prepare:
• IND/IDE briefing package, protocols, investigator brochures.
• Integrated Quality and Regulatory Summary mapping CMC and DHF content to submission sections.
• Labeling/Instructions for Use (IFU) drafts that reflect combined use.
8. Regulatory Interactions and Milestones
• Early milestone plan (example timeline, adapt as needed):
• Month 0–2: PMOA justification, internal alignment, preliminary risk analysis, identify lead center via OCP if unclear.
• Month 2–6: Pre-submission meetings with FDA; finalize nonclinical/clinical plans.
• Month 4–10: Complete pivotal bench testing, stability initiation, complete DHF design verification/validation.
• Month 6–12: Submit IND or IDE; begin first-in-human or feasibility study after clearance.
• Month 12+: Complete clinical study(ies), compile integrated submission (NDA, PMA, or appropriate route) with cross-referenced CMC and DHF.
• Include contingency buffers for additional FDA information requests (typically 30–90+ days).
9. Post-Approval/Post-Market Considerations
• Plan for post-market surveillance and post-approval studies that address long-term safety and device performance.
• Establish mechanisms for adverse event reporting that capture both device and drug-related events.
• Maintain bridging documentation for manufacturing changes that could affect the other component; regulatory pathways for changes (supplements, PMA changes, 510(k) as applicable).
10. Practical Recommendations and Next Steps
• Immediately: Produce a PMOA justification dossier and submit an OCP inquiry if assignment is uncertain.
• Prepare for a joint pre-submission meeting(s) including a consolidated briefing book mapping PMOA, CMC/DHF status, testing plans, and clinical protocols.
• Create the integrated traceability matrix linking product requirements → CMC/DHF → verification/validation → clinical endpoints.
• Assign an internal cross-functional lead (regulatory + technical + quality) to coordinate dual-center interactions and integrated documentation.
