D.2.5: Validation Review and Approval

Document ID: CODITECT-BIO-VAL-005 Version: 1.0.0 Effective Date: 2026-02-16 Classification: Internal - Restricted Owner: QA Director

Document Control

Approval History

Role	Name	Signature	Date
QA Director	[Pending]	[Digital Signature]	YYYY-MM-DD
Quality Head	[Pending]	[Digital Signature]	YYYY-MM-DD
Regulatory Affairs Director	[Pending]	[Digital Signature]	YYYY-MM-DD
CEO/Executive Sponsor	[Pending]	[Digital Signature]	YYYY-MM-DD

Revision History

Version	Date	Author	Changes	Approval Status
1.0.0	2026-02-16	QA Team	Initial release	Draft

Distribution List

Executive Leadership Team
Quality Assurance Team
Validation Team
Regulatory Affairs
Internal Audit
External Auditors (upon request)

Review Schedule

Review Type	Frequency	Next Review Date	Responsible Party
Annual Review	12 months	2027-02-16	QA Director
Post-Audit Review	As needed	N/A	Quality Head
Regulatory Update Review	As needed	N/A	Regulatory Affairs

1. Purpose and Scope

1.1 Purpose

This document establishes the procedures for reviewing, approving, and documenting validation activities for the CODITECT Biosciences Quality Management System (BIO-QMS) platform to ensure:

Independent Review - QA independence from validation execution (segregation of duties)
Regulatory Compliance - Full conformance with FDA 21 CFR Part 11 §11.100 electronic signature requirements
Evidence Completeness - All validation evidence reviewed for accuracy and completeness
Formal Approval - Multi-level approval workflow with cryptographically signed approvals
Validation Summary - Executive-level summary report documenting validation conclusions
Inspection Readiness - Preparation for FDA, EU, and third-party audits

1.2 Scope

This policy applies to:

In Scope:

QA review of validation protocols (IQ, OQ, PQ)
QA review of test execution results and evidence
Deviation review and resolution verification
Formal approval workflows per FDA Part 11
Validation Summary Report (VSR) generation
Post-validation maintenance planning
Regulatory inspection preparation

Out of Scope:

Validation protocol development (covered in D.2.1)
Evidence collection procedures (covered in D.2.4)
Routine system change control (covered in separate procedure)

1.3 Audience

Primary: QA Managers, QA Reviewers, Quality Head
Secondary: Validation Engineers, Regulatory Affairs, Auditors
Reference: Executive Leadership, FDA Inspectors

2. Validation Review Process

2.1 Review Workflow

Three-Stage Review Process:

Stage 1: Validation Lead Self-Review → Stage 2: QA Reviewer Independent Review → Stage 3: Quality Head Final Approval
     ↓                                        ↓                                            ↓
Completeness Check                      Technical Accuracy Review                   Compliance Assessment
Evidence Verification                   Deviation Resolution Review                 Risk Acceptance
Protocol Adherence                      Traceability Validation                     Business Sign-Off

Workflow Timeline:

Stage	Responsible	Timeline	Deliverable
Stage 1: Validation Lead Self-Review	Validation Engineer	2 business days	Validation Package Submission
Stage 2: QA Reviewer Independent Review	QA Manager	5 business days	QA Review Report
Stage 3: Quality Head Final Approval	Quality Director	3 business days	Validation Summary Report (VSR)
Total Timeline	—	10 business days	Approved Validation Package

2.2 Review Checklist (20+ Items)

QA Validation Review Checklist

Checklist ID: QA-VAL-CHECKLIST-v1.0 Protocol Reviewed: [Protocol ID] Reviewer: [QA Reviewer Name] Review Date: [YYYY-MM-DD]

Section 1: Protocol Completeness (5 items)

#	Check Item	Pass	Fail	N/A
1.1	Validation protocol includes all required sections per SOP	☐	☐	☐
1.2	Test cases cover 100% of URS requirements (traceability matrix verified)	☐	☐	☐
1.3	Acceptance criteria defined for each test step	☐	☐	☐
1.4	Protocol version control and approval signatures present	☐	☐	☐
1.5	Risk assessment documented and approved	☐	☐	☐

Section 2: Test Execution Evidence (7 items)

#	Check Item	Pass	Fail	N/A
2.1	All test cases executed (no skipped tests without justification)	☐	☐	☐
2.2	Pass/fail determination documented for each test step	☐	☐	☐
2.3	Evidence artifacts (screenshots, logs, queries) present for all test steps	☐	☐	☐
2.4	Evidence metadata complete (timestamp, collector, environment)	☐	☐	☐
2.5	SHA-256 hashes verified for all evidence artifacts (integrity check)	☐	☐	☐
2.6	Merkle tree root hash signature verified	☐	☐	☐
2.7	Chain of custody documented for all evidence	☐	☐	☐

Section 3: Deviations and CAPAs (4 items)

#	Check Item	Pass	Fail	N/A
3.1	All deviations classified (Critical/Major/Minor)	☐	☐	☐
3.2	Impact assessments completed for all deviations	☐	☐	☐
3.3	CAPAs created for all critical deviations	☐	☐	☐
3.4	Deviation resolutions verified with re-test evidence	☐	☐	☐

Section 4: Regulatory Compliance (5 items)

| # | Check Item | Pass | Fail | N/A | Comments | |---|------------|------|-----|----------| | 4.1 | FDA Part 11 §11.10 controls validated (audit trail, access control, etc.) | ☐ | ☐ | ☐ | | | 4.2 | Electronic signatures comply with Part 11 §11.200 (uniqueness, verification) | ☐ | ☐ | ☐ | | | 4.3 | HIPAA §164.312 encryption requirements validated (PHI protection) | ☐ | ☐ | ☐ | | | 4.4 | SOC 2 CC6 controls validated (access control, key management) | ☐ | ☐ | ☐ | | | 4.5 | EU Annex 11 requirements validated (if applicable for EU market) | ☐ | ☐ | ☐ | |

Section 5: Traceability and Documentation (4 items)

#	Check Item	Pass	Fail	N/A
5.1	Traceability matrix complete (URS → FS → DS → Protocol → Evidence)	☐	☐	☐
5.2	Forward trace validated (all requirements tested)	☐	☐	☐
5.3	Backward trace validated (all evidence linked to requirements)	☐	☐	☐
5.4	Gap analysis performed and all gaps resolved or documented	☐	☐	☐

Section 6: System Configuration (3 items)

#	Check Item	Pass	Fail	N/A
6.1	System configuration baseline documented and signed	☐	☐	☐
6.2	Software versions match validated configuration (no unauthorized changes)	☐	☐	☐
6.3	Infrastructure configuration (database, network, storage) documented	☐	☐	☐

Section 7: Approval Signatures (2 items)

#	Check Item	Pass	Fail	N/A	Comments
7.1	Validation Lead signature present (protocol execution certification)	☐	☐	☐
7.2	Electronic signature metadata complete (signer ID, timestamp, meaning)	☐	☐	☐

Review Summary:

Total Items: 30
Pass: [Count]
Fail: [Count]
N/A: [Count]
Pass Rate: [Percentage]

Review Conclusion:

☐ APPROVED - All critical items pass, proceed to Quality Head approval ☐ APPROVED WITH CONDITIONS - Minor findings, document conditions and proceed ☐ REJECTED - Critical findings, remediation required before re-submission

QA Reviewer Signature:

{
  "signature_id": "SIG-2026-02-16-QA-001",
  "signer_id": "U-9823",
  "signer_name": "John Smith",
  "signer_role": "QA Manager",
  "meaning": "QA Review of Validation Protocol VP-BIO-QMS-IQ-001",
  "signed_at": "2026-02-16T16:30:00Z",
  "auth_method": "sso_reauth",
  "signature": "ECDSA-SHA256:3045022100..."
}

2.3 Review Documentation

QA Review Report Template:

# QA Validation Review Report

**Report ID:** QA-REV-2026-02-16-001
**Protocol ID:** VP-BIO-QMS-IQ-001
**Protocol Version:** 1.0
**Review Date:** 2026-02-16
**Reviewer:** John Smith (QA Manager)

---

## Executive Summary

This report documents the QA review of the Installation Qualification (IQ) validation protocol for the BIO-QMS platform. The review was conducted in accordance with SOP-VAL-005 (Validation Review and Approval) and covered protocol completeness, test execution evidence, deviation management, and regulatory compliance.

**Review Conclusion:** APPROVED WITH CONDITIONS

**Overall Assessment:** The validation execution was thorough and well-documented. All 47 test cases were executed successfully with complete evidence artifacts. One minor deviation (DEV-2026-02-16-002) was identified and resolved. The system meets all URS requirements and is fit for intended use.

**Conditions for Approval:**
1. Update traceability matrix to include missing cross-reference for URS-047 (password complexity requirement)
2. Re-generate PDF binder with corrected Table of Contents hyperlinks
3. Add clarification note to VSR regarding performance benchmark baseline

**Expected Resolution Time:** 4 hours (administrative updates, no re-testing required)

---

## Review Findings

### Completeness (5/5 items pass)

✓ All sections present per protocol template
✓ 100% requirements coverage (156/156 URS requirements tested)
✓ Acceptance criteria clear and measurable
✓ Version control and approvals in place
✓ Risk assessment documented (21 risks identified, 18 mitigated, 3 accepted)

### Evidence Quality (7/7 items pass)

✓ 247 evidence artifacts collected
✓ Pass/fail determination documented for all 473 test steps
✓ Screenshots include timestamps and environment identifiers
✓ Database query results match expected criteria
✓ SHA-256 hashes verified for all artifacts (0 integrity failures)
✓ Merkle root signature valid (verified with public key)
✓ Chain of custody complete (automated evidence collection)

### Deviations (4/4 items pass)

✓ 2 deviations identified (1 critical, 1 minor)
✓ Impact assessments complete (15 required fields documented)
✓ CAPA created for critical deviation (CAPA-2026-02-16-003)
✓ Re-test evidence confirms resolution (TC-IQ-007 re-executed successfully)

**Deviation Detail:**

| Deviation ID | Severity | Description | Resolution |
|--------------|----------|-------------|------------|
| DEV-2026-02-16-001 | Critical | Database encryption missing for `patient_notes` field | Django model updated, migration applied, re-tested (PASS) |
| DEV-2026-02-16-002 | Minor | Traceability matrix missing cross-reference for URS-047 | Administrative correction, matrix updated |

### Regulatory Compliance (5/5 items pass)

✓ FDA Part 11 §11.10 controls validated (audit trail immutability confirmed)
✓ Electronic signatures validated (2-phase flow, signature uniqueness, re-auth)
✓ HIPAA §164.312 encryption validated (AES-256-GCM at rest, TLS 1.3 in transit)
✓ SOC 2 CC6 controls validated (key management, access control)
✓ EU Annex 11 requirements validated (electronic record integrity, audit trail)

### Traceability (4/4 items pass, 1 condition)

✓ Traceability matrix generated (156 requirements → 47 test cases → 247 evidence artifacts)
✓ Forward trace complete (all requirements tested)
✓ Backward trace complete (all evidence linked to requirements)
⚠ Gap analysis performed (3 gaps identified, 2 resolved, 1 documentation update required)

**Condition:** Update traceability matrix to include URS-047 cross-reference (4-hour timeline)

---

## Recommendations

1. **Performance Baseline:** Document current response time benchmarks (login: 243ms avg) as baseline for future regression testing
2. **Automated Integrity Checks:** Implement daily Merkle tree verification cron job to detect evidence tampering
3. **Inspector Portal:** Deploy read-only web portal for auditor access (15-minute retrieval guarantee)

---

## Approval

**QA Manager Approval:**

I have reviewed the validation package for VP-BIO-QMS-IQ-001 and found it to be complete, accurate, and compliant with regulatory requirements. The conditions noted above are administrative in nature and do not impact the validation conclusions. I recommend approval by the Quality Head.

**Signature:**

John Smith, QA Manager Digital Signature ID: SIG-2026-02-16-QA-001 Signed At: 2026-02-16T16:30:00Z

---

**Attachments:**
- QA Review Checklist (completed)
- Deviation Reports (DEV-2026-02-16-001, DEV-2026-02-16-002)
- Traceability Matrix Gap Analysis

2.4 Review Timeline Requirements

Review Type	Timeline	Trigger	Deliverable
Protocol Review (pre-execution)	3 business days	Protocol submission	Protocol approval or rejection
Interim Review (during execution)	1 business day	Deviation detection	Deviation approval or stop-work
Final Review (post-execution)	5 business days	Evidence package submission	QA Review Report
Quality Head Review	3 business days	QA Review Report approved	VSR approval

Escalation for Delays:

Day 3 (60% timeline): Email reminder to reviewer
Day 5 (100% timeline): Escalate to QA Director
Day 7 (140% timeline): Escalate to Quality Head + Executive notification

3. QA Review Procedures

3.1 QA Independence Requirement

Segregation of Duties:

Role	Can Execute Validation	Can Review Validation	Can Approve Validation
Validation Engineer	✓	✗ (conflict of interest)	✗
QA Reviewer	✗	✓	✗
QA Manager	✗	✓	✓ (QA review layer only)
Quality Head	✗	✓	✓ (final approval)

Independence Verification:

Before assigning a QA reviewer, the system MUST verify:

def verify_qa_independence(protocol_id: str, reviewer_id: str) -> bool:
    """Ensure QA reviewer did not participate in validation execution"""

    protocol = load_protocol(protocol_id)

    # Check 1: Reviewer not listed as test executor
    test_executors = protocol.get('executors', [])
    if reviewer_id in test_executors:
        raise ConflictOfInterest(f"Reviewer {reviewer_id} executed tests in {protocol_id}")

    # Check 2: Reviewer not author of protocol
    if protocol.get('author_id') == reviewer_id:
        raise ConflictOfInterest(f"Reviewer {reviewer_id} authored protocol {protocol_id}")

    # Check 3: Reviewer not in same reporting chain as executor (optional)
    # (Depends on organizational structure)

    return True

3.2 QA Review Scope

QA Review MUST Cover:

Protocol Adherence:
- All test cases executed as specified (no unauthorized deviations)
- Test data matches protocol requirements
- Environment configuration matches validated baseline
Evidence Completeness:
- All required evidence types collected (screenshots, logs, queries)
- Evidence metadata complete (timestamp, collector, environment)
- No missing evidence artifacts (gap detection)
Result Accuracy:
- Pass/fail determinations correct (actual vs. expected comparison)
- Manual review of failed tests (not just automated pass/fail)
- Statistical analysis of performance metrics (where applicable)
Deviation Management:
- All deviations detected and classified
- Impact assessments complete and accurate
- Resolutions implemented and verified
Regulatory Compliance:
- All regulatory requirements tested (FDA Part 11, HIPAA, SOC 2)
- Cross-framework control mapping validated
- Compliance evidence present and sufficient
Traceability:
- Forward trace complete (URS → Evidence)
- Backward trace complete (Evidence → URS)
- Gap analysis performed and gaps resolved

3.3 QA Review Criteria

Pass Criteria:

A validation package is approved if:

100% critical test cases pass (no failures in critical requirements)
>95% overall test pass rate (minor failures acceptable with deviation approval)
All critical deviations resolved (with re-test evidence)
Traceability complete (no untested requirements, no orphan evidence)
Evidence integrity verified (SHA-256 hashes match, Merkle tree valid)
Regulatory compliance demonstrated (all framework requirements tested)

Conditional Approval Criteria:

A validation package is approved with conditions if:

Minor documentation gaps (e.g., missing cross-references, typos)
Non-critical deviations pending (resolution plan approved, re-test scheduled)
Traceability gaps minor (e.g., 1-2 unmapped test cases, administrative fix)

Conditions MUST:

Be documented in QA Review Report
Have specific resolution criteria
Have timeline for resolution (typically 1-5 business days)
Be verified before VSR sign-off

Rejection Criteria:

A validation package is rejected if:

Critical test failures unresolved (system does not meet requirements)
Evidence integrity compromised (hash mismatches, tampered artifacts)
Major traceability gaps (>5% requirements untested)
Regulatory non-compliance (Part 11 controls not validated)
Deviations without impact assessment (risk not evaluated)

3.4 QA Finding Categories

Finding Category	Severity	Response Required	Timeline
Critical Finding	System does not meet requirement, regulatory non-compliance	Immediate remediation, re-validation	72 hours
Major Finding	Significant gap in evidence, incomplete documentation	Remediation before final approval	5 business days
Minor Finding	Administrative errors, cosmetic issues	Document in VSR, fix before archival	10 business days
Observation	Improvement opportunity, no remediation required	Document in VSR, consider for future	N/A

Finding Documentation Template:

## QA Finding

**Finding ID:** QA-FIND-2026-02-16-001
**Category:** Major Finding
**Severity:** High
**Protocol ID:** VP-BIO-QMS-IQ-001
**Test Case:** TC-IQ-009-AUDIT-TRAIL-INTEGRITY

**Description:**

Audit trail integrity chain verification test (TC-IQ-009) did not include evidence of HMAC-SHA256 signature validation for the entire audit log. Only the first 100 entries were verified, but the protocol requires verification of all 1,247 entries.

**Impact:**

- Incomplete validation of Part 11 §11.10(e) requirement (audit trail integrity)
- Risk that audit log tampering could go undetected
- Does not meet protocol acceptance criteria ("verify HMAC chain for all entries")

**Recommendation:**

Re-execute TC-IQ-009 with full audit log verification script (validation/scripts/verify-audit-chain.py --full). Expected execution time: 15 minutes. Update evidence package with new execution log.

**Resolution Timeline:** 1 business day

**Remediation Owner:** Validation Engineer (U-8472)

**Status:** OPEN

---

**Resolution:**

TC-IQ-009 re-executed on 2026-02-17T10:15:00Z with full audit log verification. All 1,247 audit entries verified successfully (0 HMAC failures). Evidence package updated with new execution log and SHA-256 hash.

**Evidence:**
- `TC-IQ-009/audit-chain-verification-full.json` (SHA256: `a3c5f8d2...`)
- `TC-IQ-009/execution-log-updated.json` (SHA256: `b7e9f3a1...`)

**Verified By:** QA Manager (U-9823)
**Verified At:** 2026-02-17T11:00:00Z
**Status:** CLOSED

4. Formal Sign-Off Process

4.1 Electronic Signature Requirements per Part 11 §11.100

FDA 21 CFR Part 11 §11.100(a): Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else.

FDA 21 CFR Part 11 §11.100(b): Before an organization establishes, assigns, certifies, or otherwise sanctions an individual's electronic signature, the organization shall verify the identity of the individual.

FDA 21 CFR Part 11 §11.100(c): Persons using electronic signatures shall, prior to or at the time of such use, certify to the agency that the electronic signatures in their system are intended to be the legally binding equivalent of traditional handwritten signatures.

BIO-QMS Implementation:

Unique Signatures: Each approver has unique ECDSA P-256 keypair (stored in HSM)
Identity Verification: Multi-factor authentication required before signature creation (password + TOTP)
Legal Binding Certification: Signed agreement on file acknowledging electronic signatures are legally binding

Signature Certification Agreement:

# Electronic Signature Certification Agreement

I, [User Name], certify that:

1. I understand that my electronic signature has the same legal force and effect as my handwritten signature.
2. I will not share my authentication credentials (password, TOTP device) with anyone.
3. I will immediately report any suspected compromise of my electronic signature to the Quality Assurance team.
4. I will use my electronic signature only for documents and records that I have personally reviewed and approved.
5. I understand that unauthorized use of electronic signatures is a violation of company policy and may result in disciplinary action.

**User ID:** [User ID]
**User Name:** [User Name]
**Role:** [Quality Head / QA Manager / etc.]
**Agreement Date:** [YYYY-MM-DD]
**Signature:** [Digital Signature ID]

4.2 Approval Authority Matrix

Document Type	Validation Lead	QA Manager	QA Director	Quality Head	Executive
Validation Protocol (pre-execution)	Certifies	Reviews	—	Approves	—
Test Execution Results	Certifies	Reviews	—	—	—
Deviation Report (Minor)	Documents	Approves	—	—	—
Deviation Report (Major)	Documents	Reviews	Approves	—	—
Deviation Report (Critical)	Documents	Reviews	Reviews	Approves	Informed
QA Review Report	—	Certifies	Reviews	—	—
Validation Summary Report	Contributes	Reviews	Reviews	Approves	Informed
Change Control (post-validation)	Reviews	Reviews	—	Approves	—

Approval Authority Definitions:

Certifies: Asserts that work was performed per procedure (executor accountability)
Reviews: Independent assessment of completeness and accuracy
Approves: Formal acceptance and authorization to proceed
Informed: Receives notification (no signature required)

4.3 Sequential Approval Workflow

Three-Step Sequential Approval:

Step 1: Validation Lead Certifies
    ↓
Evidence Package Submitted to QA
    ↓
Step 2: QA Reviewer Reviews & Approves
    ↓
QA Review Report Generated
    ↓
Step 3: Quality Head Final Approval
    ↓
Validation Summary Report Issued
    ↓
System Released to Production

Workflow Implementation:

class ValidationApprovalWorkflow:
    """
    Orchestrates sequential approval workflow for validation packages.
    Enforces Part 11 signature requirements and approval authority matrix.
    """

    APPROVAL_SEQUENCE = [
        {'role': 'VALIDATION_LEAD', 'action': 'certify', 'meaning': 'Protocol executed per specification'},
        {'role': 'QA_MANAGER', 'action': 'review', 'meaning': 'Independent review completed'},
        {'role': 'QUALITY_HEAD', 'action': 'approve', 'meaning': 'Final validation approval'}
    ]

    def submit_for_approval(self, protocol_id: str, submitter_id: str):
        """Submit validation package for approval workflow"""

        # Verify submitter is Validation Lead
        if not self._has_role(submitter_id, 'VALIDATION_LEAD'):
            raise Unauthorized(f"Only Validation Lead can submit for approval")

        # Create approval workflow instance
        workflow_id = f"APPR-{protocol_id}-{datetime.utcnow().strftime('%Y%m%d%H%M%S')}"

        workflow = {
            'workflow_id': workflow_id,
            'protocol_id': protocol_id,
            'status': 'pending',
            'current_step': 0,
            'steps': [],
            'created_at': datetime.utcnow(),
            'created_by': submitter_id
        }

        save_approval_workflow(workflow)

        # Notify first approver (Validation Lead to certify)
        self._notify_next_approver(workflow_id)

        return workflow_id

    def sign_approval_step(self, workflow_id: str, approver_id: str, signature_id: str):
        """Process approval signature at current workflow step"""

        workflow = load_approval_workflow(workflow_id)

        # Verify workflow not already complete
        if workflow['status'] == 'approved':
            raise WorkflowComplete(f"Workflow {workflow_id} already approved")

        # Verify approver has correct role for current step
        current_step = self.APPROVAL_SEQUENCE[workflow['current_step']]
        if not self._has_role(approver_id, current_step['role']):
            raise Unauthorized(f"User {approver_id} does not have role {current_step['role']}")

        # Verify signature belongs to approver
        signature = load_signature(signature_id)
        if signature['signer_id'] != approver_id:
            raise SignatureMismatch(f"Signature {signature_id} does not belong to {approver_id}")

        # Verify signature meaning matches workflow step
        expected_meaning = f"{current_step['meaning']} for {workflow['protocol_id']}"
        if signature['meaning'] != expected_meaning:
            raise SignatureMismatch(f"Signature meaning does not match workflow step")

        # Record approval step
        workflow['steps'].append({
            'step_number': workflow['current_step'],
            'role': current_step['role'],
            'action': current_step['action'],
            'approver_id': approver_id,
            'approver_name': get_user_name(approver_id),
            'signature_id': signature_id,
            'signed_at': signature['signed_at']
        })

        # Advance to next step or complete
        workflow['current_step'] += 1
        if workflow['current_step'] >= len(self.APPROVAL_SEQUENCE):
            workflow['status'] = 'approved'
            workflow['approved_at'] = datetime.utcnow()

            # Trigger VSR generation
            generate_validation_summary_report(workflow['protocol_id'])

            # Notify stakeholders
            self._notify_approval_complete(workflow_id)
        else:
            # Notify next approver
            self._notify_next_approver(workflow_id)

        save_approval_workflow(workflow)

        return workflow['status']

4.4 Conditional Approval

Conditional Approval Scenario:

QA review identifies minor findings that do not impact validation conclusions but require documentation updates.

Process:

QA Reviewer documents conditions in QA Review Report
QA Manager approves with conditions (digital signature + conditions list)
Validation Lead addresses conditions (updates documentation)
QA Manager verifies condition resolution (review updated documents)
Quality Head proceeds with final approval (conditions satisfied)

Conditional Approval Signature Meaning:

{
  "signature_id": "SIG-2026-02-16-COND-001",
  "signer_id": "U-9823",
  "meaning": "QA Review Approved with Conditions for VP-BIO-QMS-IQ-001",
  "conditions": [
    {
      "condition_id": "COND-001",
      "description": "Update traceability matrix to include URS-047 cross-reference",
      "severity": "minor",
      "resolution_timeline": "4 hours",
      "status": "open"
    },
    {
      "condition_id": "COND-002",
      "description": "Re-generate PDF binder with corrected Table of Contents hyperlinks",
      "severity": "minor",
      "resolution_timeline": "2 hours",
      "status": "open"
    }
  ],
  "signed_at": "2026-02-16T16:45:00Z"
}

Condition Resolution Tracking:

def verify_conditions_resolved(signature_id: str) -> bool:
    """Verify all conditions in conditional approval are resolved"""

    signature = load_signature(signature_id)
    conditions = signature.get('conditions', [])

    unresolved = [c for c in conditions if c['status'] != 'resolved']

    if unresolved:
        print(f"⚠ {len(unresolved)} conditions unresolved:")
        for c in unresolved:
            print(f"  - {c['condition_id']}: {c['description']}")
        return False

    print(f"✓ All {len(conditions)} conditions resolved")
    return True

4.5 Rejection Workflow

Rejection Trigger:

QA review identifies critical findings that prevent validation approval.

Process:

QA Reviewer documents findings in QA Review Report
QA Manager rejects validation package (digital signature on rejection)
Rejection notification sent to Validation Lead with findings
Remediation plan required (document corrective actions)
Re-validation required (re-execute affected test cases)
Re-submission (new approval workflow initiated)

Rejection Signature:

{
  "signature_id": "SIG-2026-02-16-REJ-001",
  "signer_id": "U-9823",
  "meaning": "QA Review Rejection for VP-BIO-QMS-IQ-001",
  "rejection_reasons": [
    {
      "finding_id": "QA-FIND-2026-02-16-003",
      "severity": "critical",
      "description": "Evidence integrity compromised - 12 artifacts with SHA-256 hash mismatches",
      "impact": "Cannot verify evidence authenticity, validation conclusions unreliable",
      "required_action": "Re-execute affected test cases with evidence collection verification enabled"
    }
  ],
  "signed_at": "2026-02-16T17:00:00Z"
}

5. Validation Summary Report (VSR) Template

5.1 VSR Purpose and Structure

Purpose:

The Validation Summary Report (VSR) is the executive-level document that:

Summarizes validation activities and results
Provides conclusion on system fitness for intended use
Documents approval signatures from all required stakeholders
Serves as the primary validation artifact for regulatory inspections

Structure (8 Sections):

Executive Summary
System Description and Scope
Validation Approach Summary
Test Execution Summary
Deviation Summary with Resolution Status
Risk Assessment Results
Conclusion and Recommendation
Approval Signature Block

5.2 VSR Template

# Validation Summary Report

**System:** CODITECT Biosciences Quality Management System (BIO-QMS)
**Validation Protocol:** VP-BIO-QMS-IQ-001 (Installation Qualification)
**Protocol Version:** 1.0
**Execution Date:** 2026-02-16
**VSR Author:** John Smith (QA Manager)
**VSR Date:** 2026-02-18
**VSR Version:** 1.0

---

## 1. Executive Summary

This Validation Summary Report documents the Installation Qualification (IQ) validation activities for the BIO-QMS platform, a cloud-based quality management system designed for biopharmaceutical manufacturers. The validation was conducted in accordance with FDA 21 CFR Part 11, HIPAA Security Rule, and SOC 2 Type II requirements.

**Validation Scope:** Installation of BIO-QMS platform version 1.0.0-rc1 in Google Cloud Platform (GCP) production environment, including:
- User authentication and authorization (multi-factor authentication)
- Electronic signature infrastructure (ECDSA P-256)
- Audit trail integrity (HMAC-SHA256 chain)
- Data encryption (AES-256-GCM at rest, TLS 1.3 in transit)
- Database backup and recovery
- Access control and role-based permissions

**Validation Approach:** Prospective validation with risk-based testing approach. Critical GxP functions prioritized for comprehensive testing.

**Test Execution Results:**
- **Total Test Cases:** 47
- **Test Steps Executed:** 473
- **Pass Rate:** 98.9% (467 steps passed, 6 steps failed initially)
- **Deviations:** 2 (1 critical, 1 minor) - both resolved
- **Evidence Artifacts Collected:** 247

**Validation Conclusion:** **VALIDATED**

The BIO-QMS platform has been successfully validated and is **fit for intended use** in a GxP-regulated environment. All critical requirements have been tested and verified. Deviations were resolved with documented corrective actions and re-testing. The system meets all FDA Part 11, HIPAA, and SOC 2 requirements.

**Recommendation:** **APPROVE FOR PRODUCTION RELEASE**

---

## 2. System Description and Scope

### 2.1 System Overview

The BIO-QMS platform is a Software-as-a-Service (SaaS) quality management system designed to support biopharmaceutical manufacturing operations. The system provides:

- **Document Management:** Controlled document creation, review, approval, and distribution
- **Change Control:** Change request tracking and approval workflows
- **CAPA Management:** Corrective and Preventive Action workflow automation
- **Training Management:** Employee training record tracking and compliance
- **Audit Management:** Internal and external audit scheduling and finding tracking
- **Deviation Management:** Deviation reporting, investigation, and resolution
- **Work Order Management:** Manufacturing work order creation and approval

### 2.2 Intended Use

The BIO-QMS platform is intended for use by biopharmaceutical manufacturers to:

1. Maintain compliance with FDA 21 CFR Part 11 (electronic records and signatures)
2. Support Good Manufacturing Practice (GMP) operations
3. Manage quality processes and documentation
4. Track and resolve quality issues (deviations, CAPAs)
5. Demonstrate regulatory compliance during inspections

### 2.3 User Roles

| Role | Description | Typical Users | Part 11 Signature Rights |
|------|-------------|---------------|--------------------------|
| **System Administrator** | Platform configuration and user management | IT staff | No |
| **Quality Manager** | Quality system oversight | Quality leadership | Yes |
| **QA Reviewer** | Quality review and approval | QA staff | Yes |
| **Document Owner** | Create and maintain documents | Department managers | Yes |
| **Trainer** | Manage training records | Training coordinators | Yes |
| **Auditor** | Read-only access for audits | Internal auditors, FDA | No |

### 2.4 Regulatory Classification

- **FDA Regulatory Class:** Part 11 Predicate Rule System (21 CFR Part 11 applies)
- **HIPAA Applicability:** Yes (PHI may be stored in clinical trial records)
- **SOC 2 Type II:** Yes (required for customer trust and RFP responses)
- **EU Annex 11:** Yes (for EU market customers)

### 2.5 Software Configuration

| Component | Version | Vendor | Validation Status |
|-----------|---------|--------|-------------------|
| **Application** | BIO-QMS 1.0.0-rc1 | CODITECT (proprietary) | This validation |
| **Database** | PostgreSQL 15.3 | PostgreSQL Global Development Group | Infrastructure validation |
| **Web Server** | Nginx 1.24.0 | Nginx, Inc. | Infrastructure validation |
| **Cloud Platform** | Google Cloud Platform | Google LLC | Vendor qualification |
| **Encryption Library** | OpenSSL FIPS 3.0.8 | OpenSSL Project | FIPS 140-2 validated |

---

## 3. Validation Approach Summary

### 3.1 Validation Strategy

**Prospective Validation:** The system was validated before production release, with all critical functions tested prior to go-live.

**Risk-Based Approach:** Testing focused on:
1. **Critical GxP Functions:** Electronic signatures, audit trails, data integrity
2. **Regulatory Requirements:** FDA Part 11, HIPAA, SOC 2 controls
3. **High-Risk Areas:** User access control, encryption, backup/recovery

**Validation Phases:**

1. **Installation Qualification (IQ):** Verify system installed per specification (this validation)
2. **Operational Qualification (OQ):** Verify system functions per design (scheduled 2026-02-20)
3. **Performance Qualification (PQ):** Verify system performs in production environment (scheduled 2026-02-24)

### 3.2 Risk Assessment

**Risk Methodology:** FMEA (Failure Mode and Effects Analysis)

**Risks Identified:** 21
**Risk Mitigation:** 18 risks mitigated through design controls and validation testing
**Residual Risks:** 3 risks accepted (documented in Risk Assessment Report)

**Top 3 Risks and Mitigations:**

| Risk ID | Risk Description | Severity | Likelihood | Mitigation | Residual Risk |
|---------|------------------|----------|------------|------------|---------------|
| RISK-001 | Audit trail tampering | Critical | Low | HMAC-SHA256 integrity chain + immutable S3 storage | Accepted (Low) |
| RISK-002 | Unauthorized data access | Critical | Medium | Multi-factor authentication + encryption at rest | Accepted (Low) |
| RISK-003 | Data loss (catastrophic failure) | Critical | Low | Multi-region backup + 4-hour RTO | Accepted (Low) |

---

## 4. Test Execution Summary

### 4.1 Test Case Summary

| Test Category | Test Cases | Test Steps | Pass | Fail | Pass Rate |
|---------------|------------|------------|------|------|-----------|
| **User Authentication** | 5 | 47 | 47 | 0 | 100% |
| **Electronic Signatures** | 8 | 89 | 89 | 0 | 100% |
| **Audit Trail Integrity** | 6 | 72 | 72 | 0 | 100% |
| **Data Encryption** | 7 | 81 | 75 | 6 | 92.6% (re-tested, 100%) |
| **Access Control** | 9 | 94 | 94 | 0 | 100% |
| **Backup and Recovery** | 4 | 38 | 38 | 0 | 100% |
| **Database Integrity** | 5 | 52 | 52 | 0 | 100% |
| **Security Controls** | 3 | 32 | 32 | 0 | 100% |
| **TOTAL** | **47** | **473** | **467** | **6** | **98.7%** |
| **After Re-Test** | **47** | **473** | **473** | **0** | **100%** |

### 4.2 Requirements Coverage

| Requirement Source | Total Requirements | Tested | Coverage % |
|--------------------|-------------------|--------|------------|
| **User Requirements Specification (URS)** | 156 | 156 | 100% |
| **FDA Part 11 §11.10** | 10 | 10 | 100% |
| **FDA Part 11 §11.200** | 3 | 3 | 100% |
| **HIPAA §164.312** | 7 | 7 | 100% |
| **SOC 2 CC6** | 6 | 6 | 100% |
| **TOTAL** | **182** | **182** | **100%** |

### 4.3 Evidence Collection Summary

| Evidence Type | Count | Total Size | Integrity Verified |
|---------------|-------|------------|-------------------|
| **Screenshots** | 89 | 124 MB | ✓ (SHA-256) |
| **Test Execution Logs** | 47 | 18 MB | ✓ (SHA-256) |
| **Database Query Results** | 52 | 3 MB | ✓ (SHA-256) |
| **API Response Captures** | 38 | 2 MB | ✓ (SHA-256) |
| **Audit Trail Excerpts** | 21 | 8 MB | ✓ (HMAC-SHA256) |
| **TOTAL** | **247** | **155 MB** | **100% Verified** |

**Evidence Integrity:** Merkle tree root hash verified with ECDSA P-256 signature (valid).

---

## 5. Deviation Summary with Resolution Status

### 5.1 Deviation Overview

| Deviation ID | Severity | Test Case | Description | Resolution Status |
|--------------|----------|-----------|-------------|-------------------|
| DEV-2026-02-16-001 | Critical | TC-IQ-007 | Database encryption missing for `patient_notes` field | ✓ RESOLVED |
| DEV-2026-02-16-002 | Minor | N/A | Traceability matrix missing URS-047 cross-reference | ✓ RESOLVED |

### 5.2 Deviation Detail

#### Deviation DEV-2026-02-16-001 (Critical)

**Description:** Database column encryption verification failed for `patient_notes` field in `clinical_records` table. Expected AES-256-GCM encryption (per HIPAA §164.312), found plaintext storage.

**Impact:** HIPAA violation (PHI not encrypted at rest), FDA Part 11 data integrity risk.

**Root Cause:** Django model field defined as `TextField` instead of `EncryptedTextField` (configuration error).

**Corrective Action:**
1. Updated Django model: `patient_notes = EncryptedTextField()`
2. Created database migration to encrypt existing records (0 records in validation environment)
3. Re-executed TC-IQ-007 with database inspection script
4. All 15 test columns verified encrypted (100% pass)

**CAPA:** CAPA-2026-02-16-003 created for preventive action (add pre-deployment encryption verification check to CI/CD pipeline)

**Resolution Evidence:**
- Updated Django model code (Git commit: `a3c5f8d2`)
- Database migration log
- TC-IQ-007 re-execution log (PASS)

**Resolution Verified By:** QA Manager (John Smith) - 2026-02-17T11:00:00Z

**Status:** ✓ CLOSED

#### Deviation DEV-2026-02-16-002 (Minor)

**Description:** Traceability matrix Excel file missing cross-reference cell for URS-047 (password complexity requirement).

**Impact:** Administrative - documentation completeness issue, no impact on validation conclusion (requirement was tested in TC-IQ-003).

**Corrective Action:** Updated traceability matrix cell C47 with cross-reference to TC-IQ-003.

**Resolution Evidence:** Updated traceability-matrix.xlsx (SHA-256: `b7e9f3a1...`)

**Resolution Verified By:** QA Manager (John Smith) - 2026-02-17T14:00:00Z

**Status:** ✓ CLOSED

---

## 6. Risk Assessment Results

**Risk Assessment Conclusion:** All identified risks have been mitigated to acceptable levels through:

1. **Design Controls:** HMAC audit trail, multi-factor authentication, encryption
2. **Validation Testing:** 100% requirements coverage, 100% pass rate after re-test
3. **Operational Controls:** Access logging, backup/recovery, monitoring

**Residual Risks Accepted:**

1. **RISK-001 (Audit Trail Tampering):** Low likelihood due to HMAC-SHA256 integrity chain and immutable S3 storage. Accepted by Quality Head.
2. **RISK-002 (Unauthorized Access):** Low likelihood due to MFA + encryption. Monitored via access logs.
3. **RISK-003 (Catastrophic Data Loss):** Low likelihood due to multi-region backup. 4-hour RTO tested and verified.

**Risk Acceptance Signature:** Quality Head (Michael Chen) - 2026-02-18T10:00:00Z

---

## 7. Conclusion and Recommendation

### 7.1 Validation Status

**Status:** ✓ **VALIDATED**

The BIO-QMS platform Installation Qualification (IQ) has been successfully completed. All 47 test cases were executed, with 100% pass rate after deviation resolution. The system has been installed per specification and is ready for Operational Qualification (OQ) testing.

### 7.2 Fitness for Intended Use

The BIO-QMS platform is **FIT FOR INTENDED USE** in a GxP-regulated biopharmaceutical manufacturing environment. The system:

- ✓ Enforces FDA Part 11 electronic signature controls
- ✓ Maintains HIPAA-compliant encryption for PHI
- ✓ Provides tamper-evident audit trail per Part 11 §11.10(e)
- ✓ Implements role-based access control with MFA
- ✓ Supports backup/recovery with 4-hour RTO
- ✓ Meets all SOC 2 Type II security controls

### 7.3 Recommendations

**Immediate Actions:**

1. **Proceed with OQ Testing:** Schedule Operational Qualification for week of 2026-02-20
2. **Deploy to Production:** Upon OQ completion, deploy validated configuration to production
3. **Initiate PQ Testing:** Schedule Performance Qualification for week of 2026-02-24

**Long-Term Actions:**

1. **Periodic Review:** Annual re-validation per SOP-VAL-006 (scheduled 2027-02-16)
2. **Change Control:** All system changes require validation impact assessment
3. **Continuous Monitoring:** Implement automated integrity checks (Merkle tree verification)

### 7.4 Periodic Review Schedule

| Review Type | Frequency | Next Review Date | Trigger |
|-------------|-----------|------------------|---------|
| **Annual Re-Validation** | 12 months | 2027-02-16 | Calendar-based |
| **Change-Driven Re-Validation** | As needed | N/A | Major system change |
| **Regulatory Update Review** | As needed | N/A | FDA guidance update |

---

## 8. Approval Signature Block

### 8.1 Validation Lead Certification

I certify that the Installation Qualification validation protocol VP-BIO-QMS-IQ-001 was executed in accordance with approved procedures. All test cases were executed as specified, evidence was collected and verified, and deviations were documented and resolved.

**Name:** Jane Doe
**Title:** Validation Lead
**User ID:** U-8472
**Signature ID:** SIG-2026-02-16-VAL-001
**Meaning:** "Certification of IQ execution for VP-BIO-QMS-IQ-001"
**Signed At:** 2026-02-16T18:00:00Z
**Signature:** `ECDSA-SHA256:3045022100e5b2c8f9a3d7e1b4c6a8f2d9e3b5c7a1f8e2d4b6c9a3f5e7d1b8c2a4f6e9d3...`

---

### 8.2 QA Review Approval

I have reviewed the validation package for VP-BIO-QMS-IQ-001 and found it to be complete, accurate, and compliant with regulatory requirements. All deviations have been resolved and verified. I recommend approval by the Quality Head.

**Name:** John Smith
**Title:** QA Manager
**User ID:** U-9823
**Signature ID:** SIG-2026-02-17-QA-001
**Meaning:** "QA Review Approval for VP-BIO-QMS-IQ-001"
**Signed At:** 2026-02-17T16:30:00Z
**Signature:** `ECDSA-SHA256:3045022100a7f3e8d2b1a5c7f9e3d8b2a4c6f1e9d3b7a2c5f8e4d1b9a6c3a8f2e5d9b7...`

---

### 8.3 Quality Head Final Approval

I have reviewed the Validation Summary Report for VP-BIO-QMS-IQ-001 and approve the system for progression to Operational Qualification (OQ) testing. The BIO-QMS platform has been validated in accordance with FDA 21 CFR Part 11, HIPAA, and SOC 2 requirements.

**Name:** Michael Chen
**Title:** Quality Head
**User ID:** U-7456
**Signature ID:** SIG-2026-02-18-QH-001
**Meaning:** "Final Validation Approval for VP-BIO-QMS-IQ-001"
**Signed At:** 2026-02-18T14:00:00Z
**Signature:** `ECDSA-SHA256:3045022100c8f2a9e5d3b1c6a4f7e2d9b8c5a3f1e6d4b7a2c9f8e5d1b3a6c4f9e7d2b5...`

---

## 9. Appendices

### Appendix A: Referenced Documents

| Document ID | Title | Version |
|-------------|-------|---------|
| VP-BIO-QMS-IQ-001 | Installation Qualification Protocol | 1.0 |
| URS-BIO-QMS | User Requirements Specification | 2.1 |
| SDD-BIO-QMS | System Design Document | 1.5 |
| SOP-VAL-001 | Validation Master Plan | 3.0 |
| SOP-VAL-005 | Validation Review and Approval | 2.0 |
| RISK-BIO-QMS-001 | Risk Assessment Report | 1.0 |

### Appendix B: Evidence Package

Evidence package location:
`gs://coditect-bio-qms-validation-evidence/VP-BIO-QMS-IQ-001/2026-02-16/`

Evidence package download:
`VP-BIO-QMS-IQ-001_Evidence-Package_2026-02-16.zip` (1.8 GB)

Evidence integrity verified: ✓ (Merkle root signature valid)

### Appendix C: Deviation Reports

- DEV-2026-02-16-001 (Critical) - Database Encryption Missing
- DEV-2026-02-16-002 (Minor) - Traceability Matrix Gap

### Appendix D: CAPA Records

- CAPA-2026-02-16-003 - Preventive Action for Encryption Verification in CI/CD

---

**END OF VALIDATION SUMMARY REPORT**

**Document Classification:** Internal - Restricted
**Distribution:** Quality Assurance, Regulatory Affairs, Executive Leadership
**Retention Period:** Life of system + 7 years (per 21 CFR Part 11)

6. Post-Validation Activities

6.1 Validation Maintenance Plan

Objective: Ensure validated state is maintained throughout system lifecycle.

Maintenance Activities:

Change Control Integration:
- All system changes assessed for validation impact
- Changes classified: No Impact / Minor Impact / Major Impact
- Re-validation required for Major Impact changes
Periodic Review:
- Annual review of validation documentation
- Verify system configuration matches validated baseline
- Update validation package if gaps identified
Continuous Monitoring:
- Automated integrity checks (Merkle tree verification)
- Access log review (unauthorized access detection)
- Performance monitoring (regression detection)
Documentation Updates:
- Maintain current validation package
- Update traceability matrix when requirements change
- Archive superseded validation documentation

6.2 Change Control Integration

Change Classification:

Change Type	Examples	Validation Impact	Re-Validation Required
No Impact	UI text changes, report formatting	None	No
Minor Impact	Non-GxP feature addition, performance optimization	Limited (regression testing)	Partial (affected modules only)
Major Impact	Audit trail modification, signature flow change	Significant	Full (IQ/OQ/PQ)

Change Control Workflow:

Change Request Submitted
    ↓
Validation Impact Assessment
    ↓
If Minor Impact: Regression Testing → QA Review → Approve
If Major Impact: Re-Validation Plan → Execute → QA Review → Approve

Validation Impact Assessment Template:

# Validation Impact Assessment

**Change Request ID:** CR-2026-03-15-001
**Change Description:** Add LDAP authentication integration
**Requestor:** IT Operations

---

## Impact Analysis

**Modules Affected:**
- User authentication service
- User provisioning service

**Validation Impact Classification:** Major Impact

**Rationale:**
- Changes authentication method (new identity verification mechanism)
- Impacts FDA Part 11 §11.200(a)(2) requirement (signature verification)
- Requires re-validation of authentication test cases

**Re-Validation Scope:**
- IQ: Re-execute TC-IQ-001 through TC-IQ-005 (authentication tests)
- OQ: Re-execute TC-OQ-001 through TC-OQ-003 (login workflows)
- PQ: No re-execution required (performance not impacted)

**Estimated Re-Validation Effort:** 24 engineer-hours (3 days)

**Approval Required:** Quality Head

---

**Assessment Completed By:** Validation Manager (Jane Doe)
**Assessment Date:** 2026-03-15
**Signature:** [Digital Signature ID]

6.3 Periodic Review Requirements

Annual Validation Review Procedure:

Review Scope:
- Validate system configuration matches baseline
- Review all change controls implemented since last review
- Verify no unauthorized system modifications
- Assess residual risk acceptance (still valid?)
Review Checklist:
- Validation documentation current and accessible
- System configuration matches validated baseline
- All changes documented in change control
- No critical deviations outstanding
- Audit trail integrity verified (sample review)
- User access reviews completed
- Backup/recovery tested within last 6 months
Review Deliverables:
- Annual Validation Review Report
- Updated Validation Maintenance Plan
- Re-validation schedule (if required)
Review Approval:
- QA Manager reviews report
- Quality Head approves

6.4 Re-Validation Triggers

Automatic Re-Validation Required:

Trigger	Re-Validation Scope	Timeline
Major Software Version (e.g., 1.x → 2.x)	Full (IQ/OQ/PQ)	Before production deployment
Infrastructure Migration (e.g., GCP → AWS)	Full (IQ/OQ/PQ)	Before cutover
Audit Trail Modification	Partial (IQ audit trail tests, OQ workflows)	Before release to production
Signature Flow Change	Partial (IQ signature tests, OQ approval workflows)	Before release to production
Encryption Algorithm Change	Partial (IQ encryption tests)	Before release to production
Database Schema Breaking Change	Partial (IQ database tests, OQ data integrity)	Before release to production

Re-Validation Not Required:

UI-only changes (no backend logic modification)
Report formatting changes
Non-GxP feature additions (isolated from validated workflows)
Security patches (if no functional change)

6.5 Continuous Monitoring Requirements

Automated Monitoring:

Evidence Integrity Monitoring:
- Daily Merkle tree verification (cron job)
- Alert if any evidence hash mismatch detected
- Quarterly full evidence package integrity audit
Configuration Drift Detection:
- Weekly configuration snapshot comparison
- Alert if validated baseline drift detected
- Monthly configuration baseline review
Access Control Monitoring:
- Real-time unauthorized access alerts
- Weekly access log review (QA team)
- Quarterly user access certification
Performance Regression Detection:
- Daily response time monitoring
- Alert if >20% degradation from baseline
- Monthly performance trend analysis

Monitoring Dashboard:

+--------------------------------------------------+
| Validation Health Dashboard                      |
+--------------------------------------------------+
| Evidence Integrity:        ✓ OK (Last check: 1h) |
| Configuration Baseline:    ✓ OK (No drift)       |
| Access Controls:           ✓ OK (0 violations)   |
| Performance:               ✓ OK (avg 215ms)      |
| Last Validation Review:    2026-02-16 (182 days) |
| Next Review Due:           2027-02-16 (183 days) |
+--------------------------------------------------+

7. Regulatory Inspection Readiness

7.1 15-Minute Retrieval Guarantee

Guarantee: Any validation artifact can be retrieved and presented to an inspector within 15 minutes.

Implementation:

Pre-Generated Packages:
- Quarterly PDF binder exports
- DVD-R backups in fireproof safe
- Indexed catalog of all validation packages
Evidence Portal:
- Web-based search interface
- Filter by protocol, test case, date range
- One-click download or preview
- Pre-signed GCS URLs (no authentication delay)
On-Demand Retrieval Script:
- Automated script downloads from GCS
- Verifies integrity (Merkle tree)
- Generates PDF binder
- Tested monthly (performance benchmark)

Retrieval SLA:

Artifact Type	Retrieval Time	Method
Single Evidence Artifact	<1 minute	Evidence Portal search + download
Full Test Case Evidence	<5 minutes	Evidence Portal filter + batch download
Complete Protocol Package	<15 minutes	Automated retrieval script
Historical Package (>1 year old)	<30 minutes	DVD-R restore + verification

7.2 Inspector Walkthrough Guide

Document: CODITECT-BIO-INSPECTOR-GUIDE-v1.0.pdf

Purpose: Provide FDA inspectors with clear navigation through validation package.

Contents:

Introduction to BIO-QMS Platform
- System overview and intended use
- Regulatory classification
- Validation approach summary
Validation Package Structure
- Directory layout explanation
- Evidence naming conventions
- How to verify evidence integrity
Key Artifacts Quick Reference
- Validation Summary Report (executive summary)
- Traceability Matrix (requirements coverage)
- Deviation Reports (all deviations and resolutions)
- Approval Signatures (Part 11 compliance)
Common Inspector Questions
- "How do you ensure audit trail integrity?" → See TC-IQ-009, HMAC chain verification
- "How do you verify electronic signatures?" → See TC-IQ-002, signature binding validation
- "How do you protect PHI?" → See TC-IQ-007, AES-256-GCM encryption verification
Evidence Portal Access
- Guest inspector account credentials
- Search and filter instructions
- Integrity verification tool usage

Inspector Guide Distribution:

Printed copy in inspection readiness binder
PDF copy in root of evidence package
Web version on evidence portal landing page

7.3 Common FDA 483 Observations and BIO-QMS Controls

FDA 483 Observation: Inadequate audit trail (cannot determine who, what, when)

BIO-QMS Control:

HMAC-SHA256 integrity chain prevents tampering
All audit entries include user ID, action, timestamp, IP address
Audit trail immutable (append-only S3 bucket with Object Lock)
Evidence: TC-IQ-009 audit trail integrity verification (PASS)

FDA 483 Observation: Electronic signatures not unique (shared credentials)

BIO-QMS Control:

Each user has unique ECDSA P-256 keypair (HSM-generated)
Signature cannot be reused (consumed flag prevents re-binding)
Multi-factor authentication required before each signature
Evidence: TC-IQ-002 signature uniqueness verification (PASS)

FDA 483 Observation: Lack of access control (unauthorized users can modify GxP records)

BIO-QMS Control:

Role-based access control (5 roles defined)
Approval workflows enforce authorization checks
Access attempts logged and monitored
Evidence: TC-IQ-005 access control verification (PASS)

FDA 483 Observation: No validation documentation available

BIO-QMS Control:

Complete validation package (IQ/OQ/PQ)
15-minute retrieval guarantee for any artifact
Evidence integrity verified (Merkle tree + digital signatures)
Inspector portal with read-only access

FDA 483 Observation: Change control does not assess validation impact

BIO-QMS Control:

All changes require validation impact assessment
Major changes trigger re-validation
Change history traceable to validation updates
Annual validation review verifies change control completeness

7.4 Mock Inspection Protocol

Objective: Prepare QA team for FDA inspection by simulating inspector walkthrough.

Frequency: Quarterly

Procedure:

Preparation (1 week before):
- Notify QA team of mock inspection date
- Assign "inspector" role to external auditor
- Prepare inspection readiness binder
Mock Inspection (4 hours):
- Inspector reviews validation package
- Inspector asks common 483 questions
- QA team retrieves evidence artifacts
- Inspector validates evidence integrity
- Inspector documents observations
Debrief (1 hour):
- Inspector presents findings
- QA team discusses improvement opportunities
- Action items assigned
Follow-Up (2 weeks):
- Address findings
- Update inspector guide if needed
- Document lessons learned

Mock Inspection Scorecard:

Criterion	Score (1-5)	Comments
Evidence Retrieval Speed		Target: <15 min
Evidence Integrity		All hashes verify
Documentation Completeness		All signatures present
Traceability Clarity		Requirements → Evidence clear
Deviation Resolution		All deviations closed
Reviewer Confidence		Can answer inspector questions

Average Score Target: 4.5/5.0

8. Cross-References

This document references and integrates with:

D.2.1: Validation Test Protocols - Protocol development and test case design
D.2.2: Validation Record Controls - Electronic record integrity and retention
D.2.3: Validation Signature Controls - E-signature binding and Part 11 compliance
D.2.4: Validation Execution Evidence Package - Evidence collection and storage
17-e-signature-architecture.md - ECDSA P-256 signature implementation details
crypto-standards-policy.md - Cryptographic algorithms and key management

Document ID: CODITECT-BIO-VAL-005 Version: 1.0.0 Classification: Internal - Restricted Next Review Date: 2027-02-16 Policy Owner: QA Director Document Location: docs/compliance/validation-review-approval.md Approval Status: Draft (pending Quality Head approval)

Confidentiality Notice: This document contains proprietary information and is intended solely for authorized personnel of CODITECT Biosciences. Unauthorized distribution is prohibited.

END OF DOCUMENT

Document Control​

Approval History​

Revision History​

Distribution List​

Review Schedule​

1. Purpose and Scope​

1.1 Purpose​

1.2 Scope​

1.3 Audience​

2. Validation Review Process​

2.1 Review Workflow​

2.2 Review Checklist (20+ Items)​

Section 1: Protocol Completeness (5 items)​

Section 2: Test Execution Evidence (7 items)​

Section 3: Deviations and CAPAs (4 items)​

Section 4: Regulatory Compliance (5 items)​

Section 5: Traceability and Documentation (4 items)​

Section 6: System Configuration (3 items)​

Section 7: Approval Signatures (2 items)​

2.3 Review Documentation​

2.4 Review Timeline Requirements​

3. QA Review Procedures​

3.1 QA Independence Requirement​

3.2 QA Review Scope​

3.3 QA Review Criteria​

3.4 QA Finding Categories​

4. Formal Sign-Off Process​

4.1 Electronic Signature Requirements per Part 11 §11.100​

4.2 Approval Authority Matrix​

4.3 Sequential Approval Workflow​

4.4 Conditional Approval​

4.5 Rejection Workflow​

5. Validation Summary Report (VSR) Template​

5.1 VSR Purpose and Structure​

5.2 VSR Template​

6. Post-Validation Activities​

6.1 Validation Maintenance Plan​

6.2 Change Control Integration​

6.3 Periodic Review Requirements​

6.4 Re-Validation Triggers​

6.5 Continuous Monitoring Requirements​

7. Regulatory Inspection Readiness​

7.1 15-Minute Retrieval Guarantee​

7.2 Inspector Walkthrough Guide​

7.3 Common FDA 483 Observations and BIO-QMS Controls​

7.4 Mock Inspection Protocol​

8. Cross-References​

Document Control Footer​

Document Control

Approval History

Revision History

Distribution List

Review Schedule

1. Purpose and Scope

1.1 Purpose

1.2 Scope

1.3 Audience

2. Validation Review Process

2.1 Review Workflow

2.2 Review Checklist (20+ Items)

Section 1: Protocol Completeness (5 items)

Section 2: Test Execution Evidence (7 items)

Section 3: Deviations and CAPAs (4 items)

Section 4: Regulatory Compliance (5 items)

Section 5: Traceability and Documentation (4 items)

Section 6: System Configuration (3 items)

Section 7: Approval Signatures (2 items)

2.3 Review Documentation

2.4 Review Timeline Requirements

3. QA Review Procedures

3.1 QA Independence Requirement

3.2 QA Review Scope

3.3 QA Review Criteria

3.4 QA Finding Categories

4. Formal Sign-Off Process

4.1 Electronic Signature Requirements per Part 11 §11.100

4.2 Approval Authority Matrix

4.3 Sequential Approval Workflow

4.4 Conditional Approval

4.5 Rejection Workflow

5. Validation Summary Report (VSR) Template

5.1 VSR Purpose and Structure

5.2 VSR Template

6. Post-Validation Activities

6.1 Validation Maintenance Plan

6.2 Change Control Integration

6.3 Periodic Review Requirements

6.4 Re-Validation Triggers

6.5 Continuous Monitoring Requirements

7. Regulatory Inspection Readiness

7.1 15-Minute Retrieval Guarantee

7.2 Inspector Walkthrough Guide

7.3 Common FDA 483 Observations and BIO-QMS Controls

7.4 Mock Inspection Protocol

8. Cross-References

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