Process Validation: synthetic data rendering - drug product, biologic

Pharmaceutical Quality (Industry), published by HL7 International / Biomedical Research and Regulation. This guide is not an authorized publication; it is the continuous build for version 1.0.0 built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/uv-dx-pq/ and changes regularly. See the Directory of published versions

Process Validation: synthetic data rendering - drug product, biologic

The HTML rendering below shows a synthetic Quality data example for Common Technical Document (CTD) Module 3: Quality, section 3.2.P.3 Manufacture , subsection 3.2.P.3.5 Process Validation and/or Evaluation for a biologic product example.

This is the same data as in the example files here in xml and in json, presented for easier viewing. Hovering on words below will show the corresponding sections of the underlying data.

Bundle [documentation R4 R5 R6]

id: bundle-product-process-validation-pq-ex3-prod-bio

Profile: http://hl7.org/fhir/uv/pharm-quality/StructureDefinition/Bundle-product-process-validation-pq

Type: collection

Process Validation Report, on Biocure

Process Validation Summary

Presentation	Formulation Lot Number	Drug Product Lot Number	Drug Product Lot Date of Manufacture	Batch Size (kg)	Units Filled	Drug Substance Lot Number
20 ml	1333224444	999909	2020-06-01	4.81	3	CAT1
50 ml	1333224444	999910	2020-06-02	4.81	3	CAT1
20 ml	1333225555	999911	2020-06-01	4.82	4	SUB2
50 ml	1333225555	999912	2020-06-02	4.82	4	SUB2
20 ml	1333226666	999913	2020-06-01	4.83	3	SUB3
50 ml	1333226666	999914	2020-06-02	4.83	3	SUB3

Diagnostic Report - Process Validation Report [Process Validation Report] (http://terminology.hl7.org/CodeSystem/pharmaceutical-report-type) [documentation R4 R5 R6]

id: processValidationReport

fullUrl: urn:uuid:b664977d-799d-a1ce-928a-5def2a9955bd

Date: 2020-12

Status: final

Code: Process Validation Report [Process Validation Report] (http://terminology.hl7.org/CodeSystem/pharmaceutical-report-type)

Triggered By: DP PROCESS VALIDATION (PlanDefinition) id: plandefinition-drug-pq-ex1-validation-protocol

Conclusion: The samples have been assessed and the conclusion is...

Table 2: Formulation Buffer Preparation Process Parameter Step

		Formulation Lot Number
Process Parameter	Acceptance Criteria	1333224444	1333225555	1333226666
Buffer vessel mixing speed (rpm)	150 rpm - 250 rpm	205	210	198
Buffer vessel mixing time (min)	45 mins - 55 mins	51	49	52

Table 3: Formulation Buffer Preparation Performance Indicator Results

		Formulation Lot Number
Performance Indicator	Acceptance Criteria	1333224444	1333225555	1333226666
pH	6.95 pH - 7.05 pH	6.9	7.1	7.2
Osmolality	250 mOsm/kg - 300 mOsm/kg	280	285	290
Conductivity	150 μS/cm - 200 μS/cm
Bioburden	50 CFU/ 100 mL - 150 CFU/ 100 mL
Bacterial Endotoxins	40 EU/mL - 120 EU/mL

Table 4: Thawing and Formulation Process Parameter Results

		Formulation Lot Number
Process Parameter	Acceptance Criteria	1333224444	1333225555	1333226666
Thawing Temp	20 °C - 24 °C
Thaw Time	NMT 3 hour
Formulation vessel mixing speed (rpm)	150 rpm - 250 rpm
Formulation vessel mixing time (min)	45 mins - 55 mins

Table 5: Thawing and Formulation Performance Indicator Results

		Formulation Lot Number
Performance Indicator	Acceptance Criteria	1333224444	1333225555	1333226666
pH	6.55 pH - 7.15 pH
Osmolality	240 mOsm/kg - 310 mOsm/kg
Conductivity	150 μS/cm - 200 μS/cm
Bacterial Endotoxins	50 EU/mL - 110 EU/mL
Polysorbate 80	25 % w/v - 55 % w/v

Table 6: Bioburden Reduction Filtration Process Parameter Results

		Formulation Lot Number
Process Parameter	Acceptance Criteria	1333224444	1333225555	1333226666
Filtration Pressure	100 psig - 150 psig

Table 7: Bioburden Reduction Filtration Performance Indicator Results

		Formulation Lot Number
Performance Indicator	Acceptance Criteria	1333224444	1333225555	1333226666
Pre-filtration Bioburden	NMT 150 CFU/ 100 mL
Post-filtration Filter Integrity (psig)	Pass (NLT 100 psig)	Pass (280)

Table 8: Media Challenge Hold Times

	Media Challenge Run
Process Parameter	Run 1	Run 2	Run 3
Media Challenge Hold Times (hours)	1.25	1.5	1.75

Table 9: Media Challenge Results

			Media Challenge Run
Performance Indicator	Acceptance Criteria	Hold Interval	Run 1	Run 2	Run 3
Bioburden	NMT 10 CFU/100 mL	Beginning End	8.0 9.0	8.5 8.6	9.5 10.1
Growth Promotion	Pass	Beginning End	Pass Pass	Pass Pass	Pass Fail

Table 11: Filtered Formulated Drug Product Performance Indicator Results

			Formulation Lot Number
Performance Indicator	Acceptance Criteria	Hold Interval	1333224444	1333225555	1333226666
SE-UHPLC Main Peak	NLT 5 %	Beginning End	8.0 8.5	9.0 9.5	10.0 10.5
SE-UHPLC Main Peak Graph		Beginning End
SE-UHPLC HMW	NLT 7 %	Beginning End	7.0 7.5	8.0 8.5	9.0 9.5

Table 16: Fill Weight Summary

		Formulation Lot Number
Performance Indicator	Acceptance Criteria	1333224444	1333225555	1333226666
Fill Weight	95 g - 105 g	Min: 9.90, Max: 9.92, Mean: 9.91

Table 17: Filling Homogeneity Quality Attributes

Quality Attribute	Justification	Analytical Method
Quantity	Demonstrates that the drug product content is maintained throughout the filling process	Protein concentration
Purity	Demonstrates the product quality is not adversely impacted over the duration of the fill through aggregation and / or oxidation	SE-UHPLC
Subvisible Particles	Quantitatively determines that subvisible particle content is maintained within specification throughout the filling process	Light obscuration

Table 18: Filling Results Summary

			Formulation Lot Number
Performance Indicator	Acceptance Criteria	Interval	1333224444	1333225555	1333226666
Protein Concentration	8 (mg/mL) - 10 (mg/mL)	Beginning Middle End	Min: 8.00, Max: 8.05 Min: 8.10, Max: 8.15 Min: 8.2, Max: 8.25
Polysorbate 80 Concentration	0.5 % w/v - 1.5 % w/v	Beginning Middle End		Min: 1.0, Max: 1.05 Min: 1.10, Max: 1.15 Min: 1.2, Max: 1.25

Table 19: Statistical Evaluation of Homogeneity Data

			95% Confidence Interval of Mean Difference
Performance Indicator	Homogeneity Acceptance Criteria	Mean Difference	Lower	Higher	Conclusion
Protein Concentration Stats	8 (mg/mL) - 10 (mg/mL)	B↔M: 8.0 B↔E: 8.05 M↔E: 8.10	B↔M: 8.15 B↔E: 8.2 M↔E: 8.25	B↔M: 8.45 B↔E: 8.3 M↔E: 8.35	Pass
Polysorbate 80 Concentration	0.5 % w/v - 1.5 % w/v

Table 20: Consistency of the Lyophilization Process

		Formulation Lot Number
Performance Indicator	Acceptance Criteria	No. of Locations	1333224444	No. of Locations	1333225555	No. of Locations	1333226666
Residual Moisture (%)	NMT 7.15 %	2	2Min: 3.1, Max: 3.2	3	34.2	3	34.4

Table 20: Lyophilization Homogeneity General Information

Drug Product Lot Number	Lot Size	Lyo Unit Used	Number of Full/Partial Shelves	Units Filled
999909	Minimum	Lyo 1	4 / 5	3
999910	Maximum			3
999911	Maximum			4
999912	Maximum			4
999913	Maximum			3
999914	Intermediate			3

Table 23: Lyophilization Homogeneity

			Formulation Lot Number
Performance Indicator	Number Of Samples	Equivalence Acceptance Criteria (90% CI Difference Criteria)	1333224444	1333225555	1333226666	Conclusion
SE-UHPLC Main Peak	12	± 5% target	91	89	92	Pass
SE-UHPLC HMW	9	± 2% target	88	93	99	Fail

Result

Found a parent (DiagnosticReport/result, id: processValidationReport fullUrl: urn:uuid:b664977d-799d-a1ce-928a-5def2a9955bd)
which is linked to this by resource.id

Observation - Buffer vessel mixing speed (rpm) [Buffer vessel mixing speed (rpm)] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-local-codes-drug-pq-example) - Text: Buffer vessel mixing speed (rpm) [documentation R4 R5 R6]

id: bufferVesselMixingSpeed1

fullUrl: urn:uuid:9c56948a-2a39-6609-1c01-4d197ea57a33

Date: 2023-01-01T12:00:00Z

Status: final

Code: Buffer vessel mixing speed (rpm) [Buffer vessel mixing speed (rpm)] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-local-codes-drug-pq-example) - Text: Buffer vessel mixing speed (rpm)

Value: 205 rpm

Subject: Lot Number: 999909 (Medication) id: medication-batch-information-drug-pq-ex1

Instantiates: Buffer vessel mixing speed (rpm) - Plan: DP PROCESS VALIDATION (PlanDefinition) id: plandefinition-drug-pq-ex1-validation-protocol (ObservationDefinition) id: bufferVesselMixingSpeed

Performer

Found a parent (Observation/performer, id: bufferVesselMixingSpeed1 fullUrl: urn:uuid:9c56948a-2a39-6609-1c01-4d197ea57a33)
which is linked to this by resource.id

Found a parent (Observation/performer, id: bufferVesselMixingSpeed2 fullUrl: urn:uuid:9c56948a-3a39-6609-1c01-4d197ea57a33)
which is linked to this by resource.id

Found a parent (Observation/performer, id: bufferVesselMixingSpeed3 fullUrl: urn:uuid:9c56948a-4a39-6609-1c01-4d197ea57a33)
which is linked to this by resource.id

Found a parent (Observation/performer, id: bufferVesselMixingTime1 fullUrl: urn:uuid:9c56948a-2a39-6609-2c01-4d197ea57a33)
which is linked to this by resource.id

Found a parent (Observation/performer, id: bufferVesselMixingTime2 fullUrl: urn:uuid:9c56948a-3a39-6609-2c01-4d197ea57a33)
which is linked to this by resource.id

Found a parent (Observation/performer, id: bufferVesselMixingTime3 fullUrl: urn:uuid:9c56948a-4a39-6609-3c01-4d197ea57a33)
which is linked to this by resource.id

Found a parent (Observation/performer, id: ph1 fullUrl: urn:uuid:44aa47fd-8964-4f96-6495-b2bec7f160e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: ph2 fullUrl: urn:uuid:54aa47fd-8964-4f96-6495-b2bec7f160e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: ph3 fullUrl: urn:uuid:54aa48fd-8964-4f96-6495-b2bec7f160e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: mediaChallengeHoldTimesStep1 fullUrl: urn:uuid:44aa47fd-9964-5f96-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: mediaChallengeHoldTimesStep2 fullUrl: urn:uuid:44aa47fd-8964-5f96-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: mediaChallengeHoldTimesStep3 fullUrl: urn:uuid:44aa47fd-8964-5f96-7495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: mediaChallengeBioburden1 fullUrl: urn:uuid:44aa47fd-9964-5f97-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: mediaChallengeBioburden2 fullUrl: urn:uuid:44aa47fd-8964-5f98-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: mediaChallengeBioburden3 fullUrl: urn:uuid:44aa47fd-8964-5f99-7495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: proteinConcentrationStats1 fullUrl: urn:uuid:54aa47fd-9965-5f97-6495-b2bec8f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: proteinConcentration1 fullUrl: urn:uuid:54aa47fd-9964-5f97-6495-b2bec8f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: polysorbate2 fullUrl: urn:uuid:54aa47fd-9964-5f97-6495-b2bec8f162e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: growthPromotion1 fullUrl: urn:uuid:54aa47fd-9964-5f97-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: growthPromotion2 fullUrl: urn:uuid:64aa47fd-8964-5f98-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: growthPromotion3 fullUrl: urn:uuid:74aa47fd-8964-5f99-7495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: postFiltrationFilterIntegrity1 fullUrl: urn:uuid:44aa47fd-8964-5f96-6495-b2bec7f161e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: osmolality1 fullUrl: urn:uuid:44aa47fd-8964-4f96-6495-b2bec7f161e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: osmolality2 fullUrl: urn:uuid:54aa47fd-8964-4f96-6495-b2bec7f162e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: osmolality3 fullUrl: urn:uuid:54aa48fd-8964-4f96-6495-b2bec7f163e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: residualMoisture1 fullUrl: urn:uuid:44ba47fd-8964-4f96-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: residualMoisture2 fullUrl: urn:uuid:44ba47fd-9964-4f96-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: residualMoisture3 fullUrl: urn:uuid:44ba47fd-9964-4f96-6496-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCMainPeak1 fullUrl: urn:uuid:44ba47fd-8964-4f96-6495-b2bec7f161e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCMainPeak2 fullUrl: urn:uuid:54ca47fd-8964-4f96-6495-b2bec7f162e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCMainPeak3 fullUrl: urn:uuid:54da48fd-8964-4f96-6495-b2bec7f163e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCMainPeakGraph1 fullUrl: urn:uuid:44ba47fd-8964-5f96-6495-b2bec7f161e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCMainPeakLyoph1 fullUrl: urn:uuid:54ba47fd-8964-4f96-6495-b2bec7f161e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCMainPeakLyoph2 fullUrl: urn:uuid:54ba47fd-8964-4f96-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCMainPeakLyoph3 fullUrl: urn:uuid:54ba47fd-8964-4f96-6495-b2bec7f161e9)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCMainPeakLyophConclusionObs fullUrl: urn:uuid:54ba48fd-8964-4f96-6495-b2bec7f161e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCHMWLyoph1 fullUrl: urn:uuid:54bb47fd-8964-4f96-6495-b2bec7f161e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCHMWLyoph2 fullUrl: urn:uuid:54ba47fd-9964-4f96-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCHMWLyoph3 fullUrl: urn:uuid:54ba47fe-8964-4f96-6495-b2bec7f161e9)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCHMWLyophConclusionObs fullUrl: urn:uuid:64ba48fd-8964-4f96-6495-b2bec7f161e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCHMW1 fullUrl: urn:uuid:44ba47fd-8964-4f97-6495-b2bec7f161e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCHMW2 fullUrl: urn:uuid:54ca47fd-8964-4f98-6495-b2bec7f162e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: SE-UHPLCHMW3 fullUrl: urn:uuid:54da48fd-8964-4f99-6495-b2bec7f163e7)
which is linked to this by resource.id

Found a parent (Observation/performer, id: fillWeight1 fullUrl: urn:uuid:55aa47fd-9964-5f97-6495-b2bec7f161e8)
which is linked to this by resource.id

Found a parent (Observation/performer, id: fillingHomogeneityConclusion-nosubject fullUrl: urn:uuid:45aa47fd-8964-4f96-6495-b2bec7f160f7)
which is linked to this by resource.id

Organization [documentation R4 R5 R6]

id: 378fbe5f-5926-3a5c-4c64-5428df877b08

fullUrl: urn:uuid:378fbe5f-5926-3a5c-4c64-5428df877b08

- Testing Lab

Identifier: 3007270600 (urn:oid:2.16.840.1.113883.4.82)

Active: true

Name: Testing Lab

Type: Analytical Testing - Release [analytical-testing-release] (http://terminology.hl7.org/CodeSystem/pharmaceutical-organization-type)

Found a parent (DiagnosticReport/result, id: processValidationReport fullUrl: urn:uuid:b664977d-799d-a1ce-928a-5def2a9955bd)
which is linked to this by resource.id

id: bufferVesselMixingSpeed2

fullUrl: urn:uuid:9c56948a-3a39-6609-1c01-4d197ea57a33

Date: 2023-01-01T12:00:00Z

Status: final

Code: Buffer vessel mixing speed (rpm) [Buffer vessel mixing speed (rpm)] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-local-codes-drug-pq-example) - Text: Buffer vessel mixing speed (rpm)

Value: 210 rpm

Subject: Lot Number: 999911 (Medication) id: medication-actual-batch-2