Pharmaceuticals and Life Sciences Solutions

1. Item (27) - Finished drug product
   Link via: [5405:11] = [27:1]

2. Batch Record Step (Custom Table)
   Link via: [5405:1] = [BatchStep:ProductionOrderNo]

3. Routing (99000763)
   Link via: [5405:Route] = [Routing:No]

[27:CustomPharmaceuticalProduct] is true
AND EXISTS(BatchStep WHERE [Completed] is false OR [VerifiedBy] is '')
AND [5405:Status]

Type: Error

Message:
BATCH RECORD INCOMPLETE - cGMP VIOLATION

Batch Number: [5405:1]
Product: [27:3]
Batch Size: [5405:8]
Scheduled Start: [5405:StartingDate]

FDA 21 CFR 211.188 - BATCH PRODUCTION AND CONTROL RECORDS:
All batch records must be complete, verified, and approved before batch release.

Incomplete Batch Steps:
[FOR EACH BatchStep WHERE Completed is false OR VerifiedBy is '':
  Step: [BatchStep:OperationNo] - [BatchStep:Description]
  Status: [IF(NOT Completed, '❌ NOT COMPLETED', IF(VerifiedBy is '', '❌ NOT VERIFIED', ''))]
  Performed By: [BatchStep:PerformedBy]
  Performed Date: [BatchStep:PerformedDate]
  Verified By: [BatchStep:VerifiedBy]
  Verified Date: [BatchStep:VerifiedDate]
]

cGMP Batch Record Requirements:
☐ All manufacturing steps completed and documented
☐ Actual yields recorded at appropriate phases
☐ In-process controls performed and results recorded
☐ Deviations documented with investigation
☐ Each step verified by second person (dual verification)
☐ Equipment identification documented
☐ Material lot numbers recorded
☐ Environmental conditions monitored
☐ Batch review completed
☐ Quality assurance approval obtained

21 CFR Part 11 Electronic Signature Requirements:
• Electronic signatures must be linked to records
• Signatures must include printed name, date, and meaning (e.g., "Performed", "Verified", "Approved")
• Records must be human-readable
• Audit trail must capture all record changes

Each batch step requires:
1. Performance by qualified operator
2. Electronic signature with timestamp
3. Independent verification by second qualified person
4. Electronic signature by verifier
5. Deviation documentation if applicable

Incomplete Documentation Consequences:
- Batch cannot be released for distribution
- FDA Form 483 observation
- Warning letter for repeat violations
- Consent decree for serious violations
- Product recall if distributed without complete records
- Criminal prosecution for falsification

Complete all batch steps and obtain required verifications before batch release.

Batch Record System: [Link to MES/LIMS]
Quality Assurance: [Contact]

[BatchStep:CriticalStep] is true
AND [BatchStep:PerformedBy] = [BatchStep:VerifiedBy]

Type: Error

Message:
DUAL VERIFICATION REQUIRED - INDEPENDENT VERIFICATION

Batch: [BatchStep:ProductionOrderNo]
Step: [BatchStep:OperationNo] - [BatchStep:Description]
Critical Step: YES

Performed By: [BatchStep:PerformedBy]
Attempted Verification By: [BatchStep:VerifiedBy]

⚠️ VERIFICATION FAILURE: Self-verification not permitted

cGMP DUAL VERIFICATION REQUIREMENT:
Critical manufacturing steps require independent verification by second qualified person.

Critical Steps Requiring Dual Verification:
• Dispensing of active pharmaceutical ingredient (API)
• Addition of potent materials
• In-process weight checks
• Cleaning verification
• Equipment setup and line clearance
• Label reconciliation
• Sampling
• Transfer between production areas
• Final product release testing

Independent Verification Means:
- Different person than who performed the step
- Qualified and trained on the procedure
- Contemporaneous verification (at time of activity)
- Not subordinate to person who performed step (when practical)

Purpose of Dual Verification:
Reduce risk of human error by having second person verify:
✓ Correct material
✓ Correct quantity
✓ Correct equipment
✓ Procedure followed correctly
✓ Documentation complete

Verification Process:
1. Operator performs critical step and documents
2. Operator signs electronically (with meaning: "Performed")
3. Operator requests independent verification
4. Second qualified person observes or verifies results
5. Verifier signs electronically (with meaning: "Verified")
6. Both signatures timestamped and captured in audit trail

Select different person for independent verification.

Available Verifiers: [List of qualified personnel on shift]

1. Item Ledger Entry (32) - Material consumption
   Link via: [ProdOrder:No] = [32:OrderNo]
   Reference Filters:
     [32:7] is 'Consumption'

2. Material Lot (Custom Table)
   Link via: [32:CustomLotNo] = [MatLot:LotNo]

[Item:CustomAPIorExcipient] is true
AND [32:CustomLotNo]

Type: Error

Message:
LOT NUMBER REQUIRED FOR MATERIAL TRACEABILITY

Production Order: [ProdOrder:No]
Finished Product: [ProdOrder:Item:Description]
Batch Number: [ProdOrder:No]

Material Consumed:
Item: [Item:Description]
Material Type: [Item:CustomMaterialType]
Quantity: [32:Quantity] [32:UOM]
Supplier: [If purchased, Vendor:Name]

FDA 21 CFR 211.188(b)(11):
Batch production records must include identification and individual weights or measures of each component used.

Material Traceability Requirements:
Every pharmaceutical material must have:
• Unique lot number
• Receipt date and receiving report number
• Identity testing results
• QA release status
• COA (Certificate of Analysis) from supplier
• Storage conditions
• Expiration or retest date

Lot Genealogy Purpose:
Links raw materials through batch to finished product enabling:
1. FORWARD TRACEABILITY: Which finished product batches contain this material lot?
2. BACKWARD TRACEABILITY: Which material lots were used in this finished batch?
3. RECALL SCOPE: Identify all affected batches if material issue discovered
4. INVESTIGATION: Root cause analysis for quality issues
5. REGULATORY INSPECTION: Demonstrate chain of custody

Critical Material Tracking:
API (Active Pharmaceutical Ingredient):
- COA from API manufacturer
- Potency and purity results
- Synthesis batch number
- DMF (Drug Master File) reference

Excipients:
- Supplier certification
- Functionality testing
- Absence of contaminants

For This Transaction:
1. Scan material container label (if barcoded)
2. Enter lot number from container label
3. Verify lot is QA released
4. Verify lot is within expiration/retest date
5. Record lot in batch genealogy

System will create traceability link:
[Material Lot] → [Batch] → [Finished Product Batch]

Cannot proceed without material lot number.

Material Lot Lookup: [Search available lots]

[MaterialLot:QAStatus]

Type: Error

Message:
MATERIAL NOT RELEASED BY QA

Material: [Item:Description]
Lot Number: [MaterialLot:LotNo]
Supplier: [MaterialLot:VendorName]
QA Status: [MaterialLot:QAStatus]

Quality Assurance Release Status:
Current Status: [MaterialLot:QAStatus]
Status Options: Quarantine → Testing → Released / Rejected

Material Status Definitions:

QUARANTINE:
- Material received but not yet sampled and tested
- Physically segregated in quarantine area
- Cannot be used in production

TESTING:
- Sample submitted to QA lab
- Testing in progress per specification
- Cannot be used until testing complete

RELEASED:
- All testing complete and specifications met
- Certificate of Analysis (COA) approved
- Authorized for use in production
- ✓ OK TO USE

REJECTED:
- Failed specification testing
- Not suitable for intended use
- Must be returned to supplier or destroyed
- ❌ CANNOT USE

This Material Lot Status:
Status: [MaterialLot:QAStatus]
Received Date: [MaterialLot:ReceiptDate]
Sampled Date: [MaterialLot:SampleDate]
QA Release Date: [MaterialLot:ReleaseDate]
Approved By: [MaterialLot:QAApprover]

[IF([MaterialLot:QAStatus] is 'Quarantine',
'Material is in quarantine awaiting sampling and testing.
Cannot use until QA releases.

Required Actions:
☐ QA samples material per sampling plan
☐ Lab performs identity, purity, potency testing
☐ Results meet specification
☐ QA approves COA
☐ QA changes status to Released
', '')]

[IF([MaterialLot:QAStatus] is 'Testing',
'Material testing is in progress.

Testing Status:
Tests Required: [List from specification]
Tests Complete: [List completed tests]
Tests Pending: [List remaining tests]
Expected Completion: [Date]

Contact QA Lab to expedite if urgent.
', '')]

[IF([MaterialLot:QAStatus] is 'Rejected',
'Material has been REJECTED by Quality Assurance.

Rejection Reason: [MaterialLot:RejectionReason]
Failed Tests: [List of failed specifications]

This lot cannot be used in production.

Disposition:
☐ Return to supplier for credit
☐ Quarantine for reprocessing (if applicable)
☐ Destroy per waste disposal procedures

Select different material lot that is QA Released.
', '')]

cGMP Requirement:
Only materials released by Quality Assurance may be used in drug manufacturing.

Using non-released materials results in:
- Invalid batch
- Batch must be destroyed
- Serious cGMP violation
- FDA enforcement action

Available Released Lots: [List of Released lots for this material]

([BatchStep:ActualYield] < [BatchStep:ExpectedYield] * 0.95
 OR [BatchStep:ActualYield] > [BatchStep:ExpectedYield] * 1.05)
AND [BatchStep:DeviationNo]

Type: Error

Message:
YIELD DEVIATION - INVESTIGATION REQUIRED

Batch: [BatchStep:ProductionOrderNo]
Product: [ProdOrder:Item:Description]
Step: [BatchStep:OperationNo] - [BatchStep:Description]

Yield Variance:
Theoretical Yield: [BatchStep:ExpectedYield] [UOM]
Actual Yield: [BatchStep:ActualYield] [UOM]
Variance: [[ActualYield - ExpectedYield] / ExpectedYield × 100]%

⚠️ EXCEEDS ACCEPTABLE YIELD VARIANCE (±5%)

FDA 21 CFR 211.192 - PRODUCTION RECORD REVIEW:
Any unexplained discrepancy or failure of a batch to meet specifications must be investigated.

Deviation Management Process:

1. DOCUMENT DEVIATION
   ☐ Initiate deviation report
   ☐ Describe deviation in detail
   ☐ Record when deviation was discovered
   ☐ Identify person reporting deviation

2. IMMEDIATE ACTIONS
   ☐ Assess impact on product quality
   ☐ Segregate affected material/product
   ☐ Prevent distribution if quality impacted
   ☐ Implement containment actions

3. INVESTIGATION
   ☐ Assign investigation to qualified person
   ☐ Determine root cause
   ☐ Review related batches (same period/equipment)
   ☐ Assess extent of impact

4. CORRECTIVE ACTIONS
   ☐ Implement immediate correction
   ☐ Address root cause
   ☐ Prevent recurrence

5. PREVENTIVE ACTIONS (CAPA)
   ☐ Identify systematic improvements
   ☐ Update procedures if needed
   ☐ Training if human error identified
   ☐ Equipment modification if appropriate

6. EFFECTIVENESS CHECK
   ☐ Verify corrective actions effective
   ☐ Monitor for recurrence
   ☐ Close deviation after verification

Possible Root Causes for Yield Variance:
LOW YIELD:
- Material loss during transfer
- Equipment holdup
- Sampling removed material
- Spillage
- Calculation error
- Process inefficiency

HIGH YIELD:
- Excess material added (serious concern)
- Foreign material contamination
- Moisture uptake
- Calculation error
- Incomplete mixing from previous batch

Yield variance >10% is particularly concerning and may indicate:
- Process out of control
- Equipment malfunction
- Operator error
- Calculation error

Cannot complete batch step until deviation documented and investigated.

Initiate Deviation Report: [Form link]
Quality Assurance: [Contact]

[CAPA:ImplementationDate] + [CAPA:EffectivenessCheckPeriod] < [T]
AND [CAPA:EffectivenessVerified]

To: quality.manager, [CAPA:ResponsiblePerson]
Subject: CAPA Effectiveness Check Overdue - [CAPA:No]

Body:
CAPA EFFECTIVENESS VERIFICATION REQUIRED

CAPA Number: [CAPA:No]
Originating Deviation: [CAPA:DeviationNo]
Issue: [CAPA:ProblemDescription]
Root Cause: [CAPA:RootCause]

Corrective Actions Implemented:
[FOR EACH action in CAPA:
  Action: [Action description]
  Implemented: [Implementation date]
  Implemented By: [Person]
]

Implementation Date: [CAPA:ImplementationDate]
Effectiveness Check Due: [CAPA:ImplementationDate + Period]
Days Overdue: [[T] - [Due date]]

CAPA EFFECTIVENESS VERIFICATION:
After implementing corrective/preventive actions, must verify actions are effective.

Effectiveness Verification Methods:
1. TREND ANALYSIS
   Review metrics before and after CAPA implementation
   Expected: Reduction or elimination of problem

2. PROCESS MONITORING
   Monitor process performance over time period
   Typical periods: 30 days, 90 days, or several production batches

3. AUDIT/INSPECTION
   Verify new procedure being followed
   Check training records if training was action

4. TESTING
   Retest to confirm issue resolved

For This CAPA:
Original Issue: [CAPA:ProblemDescription]
Occurrence Frequency Before: [CAPA:FrequencyBefore]
Monitoring Period: [CAPA:EffectivenessCheckPeriod] days

Effectiveness Check Questions:
☐ Have there been any recurrences of the original problem?
☐ Are new procedures being followed consistently?
☐ Have relevant personnel been trained?
☐ Have process metrics improved?
☐ Are preventive measures sustainable?

Data to Review:
- Deviation reports since implementation (filter by similar type)
- Batch records (check for similar issues)
- Process monitoring data
- Training records
- Audit findings

Effectiveness Determination:
✓ EFFECTIVE: No recurrence, metrics improved, procedures followed
✗ NOT EFFECTIVE: Problem recurred, metrics unchanged, need additional actions

If Not Effective:
- Revise corrective actions
- Investigate why initial actions insufficient
- Implement enhanced actions
- Schedule new effectiveness check

Complete effectiveness verification within 7 days.

CAPA System: [Link]
Trend Analysis Report: [Link to metrics dashboard]

[ChangeControl:Status] is 'Initiated'
AND [ChangeControl:ImpactAssessment]

To: [ChangeControl:Initiator], quality.engineering
Subject: Impact Assessment Required - Change Control [ChangeControl:No]

Body:
CHANGE CONTROL IMPACT ASSESSMENT

Change Control: [ChangeControl:No]
Initiated By: [ChangeControl:InitiatorName]
Date Initiated: [ChangeControl:InitiatedDate]

Proposed Change:
Type: [ChangeControl:ChangeType]
Description: [ChangeControl:ChangeDescription]
Reason: [ChangeControl:Justification]

Affected Areas:
Product: [ChangeControl:ProductAffected]
Process: [ChangeControl:ProcessAffected]
Equipment: [ChangeControl:EquipmentAffected]
Material: [ChangeControl:MaterialAffected]
Specification: [ChangeControl:SpecificationAffected]

IMPACT ASSESSMENT REQUIRED:
FDA expects pharmaceutical companies to have robust change control systems.

ICH Q10 Pharmaceutical Quality System:
Change control ensures changes are proposed, evaluated, approved, implemented, and verified.

Impact Assessment Areas:

1. PRODUCT QUALITY
   ☐ Will change affect product safety?
   ☐ Will change affect product efficacy?
   ☐ Will change affect product quality attributes?
   ☐ Impact on stability?

2. VALIDATION STATUS
   ☐ Does change affect validated process?
   ☐ Is revalidation required?
   ☐ Is protocol execution needed?
   ☐ Qualification studies required?

3. REGULATORY
   ☐ Does change require regulatory notification?
   ☐ Prior approval supplement required (major change)?
   ☐ Changes being effected supplement (moderate)?
   ☐ Annual report notification (minor)?
   ☐ Multiple markets affected?

4. DOCUMENTATION
   ☐ Which SOPs require revision?
   ☐ Which specifications require revision?
   ☐ Batch record updates needed?
   ☐ Training materials updates?
   ☐ Quality agreements affected?

5. MATERIALS/EQUIPMENT
   ☐ New materials required?
   ☐ Equipment qualification needed?
   ☐ Calibration requirements changed?

6. RISK ASSESSMENT
   ☐ What could go wrong?
   ☐ Likelihood of risk?
   ☐ Severity if occurs?
   ☐ Mitigation strategies?

Change Classification:
MINOR: Low risk, no regulatory notification
MODERATE: Medium risk, CBE-30 supplement
MAJOR: High risk, prior approval required

Required Approvals Based on Impact:
• Quality Assurance: All changes
• Quality Engineering: Process/equipment changes
• Regulatory Affairs: Changes requiring submission
• Manufacturing: Process changes
• Validation: Changes to validated systems
• Management: Major changes

Complete impact assessment within 5 business days.

Impact Assessment Form: [Template]
Change Control System: [Link]

[ChangeControl:Status] is 'Implementing'
AND [ChangeControl:ApprovalComplete]

Type: Error

Message:
CHANGE IMPLEMENTATION NOT AUTHORIZED

Change Control: [ChangeControl:No]
Description: [ChangeControl:ChangeDescription]
Status: [ChangeControl:Status]

APPROVAL STATUS:
[FOR EACH required approver:
  Approver: [Department/Role]
  Status: [IF(Approved, '✓ APPROVED ' + [Date], '❌ PENDING')]
  [IF(Rejected, '✗ REJECTED: ' + [Rejection reason])]
]

Missing Approvals:
[List departments/roles that haven't approved]

cGMP CHANGE CONTROL REQUIREMENT:
Changes must be formally approved before implementation.

Change Control Process:
1. Initiation → 2. Impact Assessment → 3. Approval → 4. Implementation → 5. Verification

Current Stage: Approval (stage 3)
Cannot proceed to Implementation until all approvals obtained.

Consequences of Unauthorized Changes:
- Unapproved change is a cGMP violation
- Batch produced under unauthorized conditions may be invalid
- Regulatory action (Form 483, Warning Letter)
- Consent decree for repeated violations
- Loss of regulatory approval
- Criminal prosecution in extreme cases

"Approved" means:
• All required functional areas have reviewed
• Each reviewer has electronically signed approval
• No outstanding rejections or requests for revision
• Change Control Coordinator has verified complete

If Urgent Change Needed:
Some systems allow "emergency change" process:
1. Document emergency justification
2. Implement with limited approval
3. Complete full approval process retrospectively
4. Verify change was appropriate

This change does not qualify for emergency process.

Wait for all approvals before implementing change.

Pending Approvers: [Contact list with reminder emails]
Change Control Coordinator: [Contact]

[Item:CustomPrescriptionDrug] is true
AND [ProductionOutput:SerialNumber] is ''
AND [ProductionOutput:PackagingLevel]

Type: Error

Message:
PRODUCT SERIALIZATION REQUIRED - DSCSA

Batch: [ProductionOutput:BatchNo]
Product: [Item:Description]
NDC: [Item:CustomNDC]
Packaging Level: [ProductionOutput:PackagingLevel]
Quantity: [ProductionOutput:Quantity]

DRUG SUPPLY CHAIN SECURITY ACT (DSCSA):
FDA requires serialization of prescription drug packages for traceability.

Serialization Requirements:

SALEABLE UNIT (Individual Package):
- Unique serial number
- 2D Data Matrix barcode
- Human-readable interpretation

Required Data Elements:
• Product Identifier (NDC or GTIN)
• Serial Number (unique to this package)
• Lot Number
• Expiration Date

Data Format: GS1 SGTIN (Serialized Global Trade Item Number)

HOMOGENEOUS CASE:
- Contains packages with same product/lot/expiration
- Serial number for case
- Aggregation linking case to contained packages

Serial Number Generation:
Serial numbers must be:
✓ Unique per GTIN
✓ Randomized (not sequential)
✓ Non-intelligible (cannot infer information from serial)
✓ Maintained in repository
✓ Reported to FDA
✓ Transferred in transaction information

2D Barcode Requirements:
- GS1 Data Matrix
- Minimum size per package dimensions
- Verification: ISO/IEC 15415 grade
- Placement: Per artwork specifications

DSCSA Traceability Events:
1. COMMISSION: Serial number assigned during packaging
2. AGGREGATION: Package into case (parent-child relationship)
3. SHIPPING: Transfer to wholesaler with transaction data
4. RECEIVING: Wholesaler receives and verifies
5. DECOMMISSION: Dispensed to patient or destroyed

For This Transaction:
1. Request serial numbers from Serialization System
2. Print 2D Data Matrix barcode on label
3. Apply label to package
4. Vision system verifies barcode quality
5. Record commission event
6. If packaging into cases, record aggregation

Serial Number Repository:
All serial numbers must be maintained in repository enabling:
- Verification at each supply chain step
- Investigation of suspect/illegitimate products
- Recall targeting specific serial numbers

Consequences of Non-Serialization:
- Cannot distribute product (violation of DSCSA)
- FDA enforcement action
- Product quarantine
- Rework to apply serialization
- Delayed shipments

Integrate with Serialization System: [Link]
Vision Inspection System: [Status]

EXISTS(SerialNumber WHERE [GTIN] = [Current:GTIN]
                     AND [SerialNumber] = [Current:SerialNumber]
                     AND [AssignedDate] < [T]

Type: Error

Message:
DUPLICATE SERIAL NUMBER DETECTED

Product: [Item:Description]
GTIN: [Item:GTIN]
Serial Number: [SerialNumber]

⚠️ This serial number has already been assigned.

Previous Assignment:
Serial Number: [PreviousAssignment:SerialNumber]
Assigned Date: [PreviousAssignment:AssignedDate]
Batch: [PreviousAssignment:BatchNo]
Packaging Line: [PreviousAssignment:PackagingLine]
Status: [PreviousAssignment:Status]

DSCSA REQUIREMENT:
Serial numbers must be unique within a GTIN (product identifier).

Duplicate Serial Number Causes:
1. Serialization system error
2. Rework without decommissioning original serial
3. Serial number pool exhausted
4. Database synchronization issue
5. Manual entry error

Consequences of Duplicate Serials:
- Traceability broken (cannot distinguish packages)
- Supply chain partners cannot verify authenticity
- Recall complications (wrong product might be targeted)
- DSCSA non-compliance
- FDA enforcement

Required Actions:
1. STOP packaging line immediately
2. Quarantine packages with duplicate serials
3. Investigate root cause
4. Decommission invalid serials in repository
5. Request new serial number pool
6. Resume packaging with valid serials
7. Document incident in deviation system

If Rework Situation:
- Original serial must be decommissioned in repository before reassignment
- Ideally, assign new serial rather than reusing
- Document reason for serial change

Serial Number Management:
- Request pools in advance
- Monitor pool depletion
- Automatic pool replenishment
- Validation checks before assignment

Serialization System Administrator: [Contact]
Quality Assurance: [Contact - for deviation documentation]