Backing Membrane Integrity Validation in Transdermal Patches Manufacturing
All equipment used in this process validation must be duly qualified and validated for its intended use and performance specifications. Equipment qualification (IQ/OQ/PQ) is assumed to be completed prior to this process validation.
Introduction to Backing Membrane Integrity in Transdermal Patch Manufacturing
Backing membranes play a critical role in transdermal patch dosage forms, serving as a protective barrier and structural component. Their integrity directly influences the patch’s performance, patient safety, and overall product quality. The validation of backing membrane integrity ensures that the backing membrane consistently meets all established specifications. This step is essential in supporting process validation efforts within the scope of cGMP guidelines for pharmaceutical manufacturing. In practice, integrity validation helps mitigate risks of leakage, contamination, and premature drug release, which could otherwise compromise the Quality Target Product Profile (QTPP).
Role of Backing Membrane Integrity in cGMP and Process Consistency
To comply with current Good Manufacturing Practices (cGMP), all critical components and manufacturing steps must be controlled and validated. The backing membrane integrity validation is integral to cGMP because it confirms that each transdermal patch consistently meets predefined quality attributes throughout production. This validation supports the continuous assurance of product performance, safety, and efficacy. In process validation terms, backing membrane integrity acts as a control point that reflects the robustness of the adhesive and lamination processes. Maintaining consistent membrane integrity reduces batch-to-batch variability and improves production yield, traceability, and documentation, meeting regulatory expectations.
Defining the Quality Target Product Profile (QTPP) Related to Backing Membrane
Begin by precisely defining the QTPP elements influenced by the backing membrane. Key components in this context include:
- Barrier Functionality: The membrane must prevent drug diffusion to the external environment and protect the drug layer from moisture, oxygen, and mechanical damage.
- Mechanical Strength: It must possess adequate tensile strength and flexibility to endure handling, storage, and application without failure.
- Adhesion Compatibility: Compatibility with the adhesive layer without compromising adhesive strength or causing delamination.
- Chemical Inertness: Non-reactive with drug substances and excipients to maintain stability.
- Appearance: Uniformity and absence of defects such as pinholes, cracks, or bubbles that could impair barrier integrity.
Establishing these objectives upfront allows alignment of the validation process toward ensuring that the backing membrane consistently contributes to achieving the overall QTPP.
Desired Attributes of the Backing Membrane
The following attributes define the desired characteristics to be maintained through the backing membrane integrity validation:
- Physical Integrity: No perforations, tears, or thinning areas that could jeopardize the barrier.
- Uniform Thickness: Maintains consistent thickness to guarantee reliable barrier properties and mechanical strength.
- Flexibility: Sufficient elasticity to accommodate skin movement without cracking or detachment.
- Adhesion Compatibility: Must not interfere chemically or physically with adhesive layers or drug formulation.
- Thermal Stability: Ability to withstand manufacturing and storage temperature conditions without physical or chemical alteration.
These desired attributes establish baseline performance requirements against which validation testing and monitoring parameters can be derived.
Impact of Backing Membrane Integrity on the QTPP
A compromised backing membrane can detrimentally affect key product quality parameters and ultimately patient safety and efficacy. Impacts include but are not limited to:
- Drug Stability: Breaches in the backing allow moisture ingress or oxygen exposure, accelerating drug degradation.
- Consistent Drug Delivery: Altered membrane properties can change the diffusion or evaporation rate, causing dose variance.
- Adhesion Variability: Membrane defects can disrupt adhesive uniformity, leading to patch lift-off or uneven application.
- Microbial Contamination Risk: Integrity breaches may allow microbial ingress, undermining product sterility or microbial limits compliance.
Therefore, establishing rigorous integrity validation protocols ensures that the backing membrane effectively maintains the QTPP attributes throughout the product lifecycle.
Critical Quality Attributes (CQAs) of the Backing Membrane
Identify and characterize the CQAs that directly influence the backing membrane performance. These typically include:
- Permeability: The intrinsic barrier capacity against gas or moisture.
- Tensile Strength and Elongation: Measures of the mechanical robustness and flexibility.
- Thickness Uniformity: Variability across the membrane sheet.
- Visual and Microscopic Defect Inspection: Detection of physical imperfections such as holes or microcracks.
- Adhesion Compatibility Testing: Ensures membrane does not adversely affect the adhesive bond strength.
Documenting critical limits, target values, and acceptable ranges for each CQA is essential for effective monitoring and control during manufacturing and validation phases.
Key Physical and Functional Properties for Validation Testing
Validation of the backing membrane integrity requires selection of key physical and functional properties that can be reliably and reproducibly assessed. Implement the following stepwise approach:
- Visual Inspection: Set up systematic protocols for visual and microscopic examination of backing membranes in-process and post-production for detecting apparent defects.
- Leak and Pinhole Detection: Employ nondestructive methods such as vacuum or pressure decay tests, dye penetration, or electrical conductivity tests to identify membrane breaches.
- Thickness Measurement: Use calibrated gauges or micrometers to measure membrane thickness at multiple points to ensure uniformity.
- Tensile Strength and Elongation Testing: Perform mechanical testing using standardized equipment (e.g., tensile tester) to confirm the membrane meets predefined mechanical criteria.
- Barrier Performance Evaluation: Measure water vapor transmission rate (WVTR) or oxygen permeability to verify the functional barrier property under relevant conditions.
- Adhesion Compatibility Assessment: Conduct peel tests or adhesion strength evaluations in combination with adhesives and drug layers to confirm physical and chemical compatibility.
- Thermal and Environmental Stress Testing: Simulate manufacturing and storage conditions to verify membrane resilience against temperature and humidity fluctuations.
Integrate these testing methods into your validation protocol to generate a comprehensive data set that supports demonstration of consistent backing membrane integrity.
Ensuring Backing Membrane Integrity Validation in Transdermal Patch Manufacturing
All equipment used in this process validation must be duly qualified and validated for its intended use and performance specifications. Equipment qualification (IQ/OQ/PQ) is assumed to be completed prior to this process validation.
Desired Attributes of Backing Membranes in Transdermal Patches
A thorough understanding of the desired attributes of backing membranes is essential to establish reliable validation criteria. These attributes include:
- Impermeability: Prevents permeation of drug substances and environmental contaminants.
- Flexibility: Allows conformability to the skin surface without cracking or delamination.
- Adhesion Compatibility: Supports firm and uniform adhesion with the adhesive matrix and patch layers.
- Chemical Stability: Resistant to degradation or leaching when in contact with active pharmaceutical ingredients or excipients.
- Mechanical Strength: Sufficient toughness to resist puncture and tearing during handling and application.
Impact of Backing Membrane Integrity on the Quality Target Product Profile (QTPP)
The backing membrane integrity directly impacts several critical parameters within the QTPP, such as:
- Drug Release Consistency: Intact membranes ensure predictable drug diffusion kinetics, maintaining therapeutic efficacy.
- Patient Safety: Prevents exposure to the drug or contamination from external sources, reducing irritation or adverse effects.
- Patch Adhesion and Wearability: Intact backing supports adhesive layers, ensuring the patch remains effective for the prescribed wear duration.
- Storage Stability: Maintains physical integrity to protect the active formulation during shelf life under varying environmental conditions.
Critical Quality Attributes (CQAs) Related to Backing Membrane Integrity
Identifying and controlling CQAs is central to validating backing membrane integrity. These CQAs include:
- Pinholes and Microvoids: Absence of microscopic defects that could compromise barrier function.
- Adhesion Strength: Measured bond strength between the backing membrane and adhesive layer.
- Thickness Uniformity: Consistent membrane thickness within defined tolerance limits.
- Delamination Resistance: Resistance to layer separation under stress or environmental exposure.
- Surface Integrity: Free from physical damage such as cracks, scratches, or particulate contamination.
Key Properties to Monitor During Backing Membrane Integrity Validation
Proper validation requires ongoing monitoring of key physical and functional properties, including:
- Visual Inspection: Routine examination under magnification to detect visible defects and contamination.
- Leak Testing: Techniques such as bubble emission or vacuum decay to identify breaches in impermeability.
- Mechanical Testing: Tensile strength and elongation tests to quantify membrane durability.
- Adhesion Testing: Peel tests to verify consistent bonding between layers.
- Environmental Stress Testing: Exposure to temperature and humidity extremes to simulate storage and use conditions.
Introduction to Backing Membrane Integrity Validation in Transdermal Patch Manufacturing
Backing membrane integrity is a critical quality attribute in transdermal patch manufacturing, ensuring the patch’s protective layer remains intact to maintain drug stability and adhesion until application. This validation confirms that the backing membrane consistently meets structural and functional requirements during production. The following step-by-step guide outlines an in-depth process validation approach directed at pharmaceutical manufacturing professionals involved in transdermal patch production.
Conduct Risk Assessment and Failure Mode and Effects Analysis (FMEA)
- Identify potential failure points related to backing membrane integrity, including:
- Membrane punctures or tears during cutting or handling.
- Delamination or material degradation from environmental exposure.
- Inadequate adhesion between the membrane and the drug reservoir layer.
- Irregular membrane thickness or defects introduced during film extrusion or lamination.
- Assign severity, occurrence, and detectability ratings to each failure mode based on historical data, equipment capabilities, and process controls.
- Severity: Impact on product quality, patient safety, or regulatory compliance.
- Occurrence: Likelihood that the failure will happen during manufacturing.
- Detectability: Probability that the failure mode will be identified before product release.
- Calculate Risk Priority Numbers (RPN) and prioritize failure modes for mitigation, focusing on high severity and high occurrence risks such as pinholes or punctures.
- Document the FMEA to inform design of the validation protocol and control strategy.
Define Critical Process Parameters (CPPs) Affecting Backing Membrane Integrity
- Evaluate the manufacturing steps that may impact membrane integrity, including:
- Lamination temperature and pressure.
- Cutting and slitting blade sharpness and speed.
- Handling and transport speed to minimize mechanical stress.
- Environmental conditions such as humidity and temperature during storage and processing.
- Select CPPs based on their influence on membrane integrity, prioritizing:
- Lamination pressure within specified limits to prevent membrane damage or delamination.
- Blade sharpness and cutting speed to avoid membrane tearing.
- Environmental controls to prevent moisture-induced weakening.
- Include CPPs in the process flow diagram and prepare for Design of Experiments (DoE) to optimize these parameters.
Design of Experiments (DoE) for Process Optimization
- Develop a factorial or response surface DoE to assess the effects of CPP variations on backing membrane integrity.
- Use measurable outputs such as pinhole counts, adhesion strength, and puncture resistance as response variables.
- Include a range of temperatures, pressures, cutting speeds, and environmental conditions within defined operational ranges.
- Conduct experiments using representative batches under controlled conditions, ensuring statistically significant sample sizes.
- Analyze data to identify optimal CPP ranges that maximize membrane integrity without compromising throughput or other quality attributes.
- Set acceptance criteria for each CPP based on DoE outcomes and regulatory expectations.
Develop Control Strategy and Monitoring Plan
- Establish in-process controls related to backing membrane integrity. Key controls include:
- Visual inspection under magnification to detect membrane defects such as pinholes or tears.
- Tensile and puncture resistance testing of membrane samples at defined intervals.
- Adhesion testing to confirm that the membrane remains firmly bonded to the patch layers.
- Continuous monitoring of lamination temperature, pressure, and cutting speed via calibrated sensors.
- Define sampling frequency for inspection and physical testing based on process capability and risk assessment results.
- Create alert and action limits for CPPs and quality attributes that trigger immediate review and corrective actions.
- Incorporate these controls into the batch production record to facilitate traceability and compliance.
Sampling and Decision Points During Validation and Routine Manufacture
- Identify sampling locations such as:
- Post-lamination prior to cutting.
- Post-cutting before batch release.
- Random finished product samples from each batch.
- Define sample sizes and frequency derived from statistical sampling plans (e.g., ANSI/ASQ Z1.4) augmented by risk-based considerations.
- At each sampling point perform:
- Visual and microscopic membrane inspections for integrity breaches.
- Mechanical testing (puncture, tensile) according to predetermined protocols.
- Adhesion strength measurements to ensure membrane resilience during storage and use.
- Implement decision rules:
- Pass criteria based on acceptance limits determined during DoE and prior validation studies.
- Rejection or hold criteria if defect rates or mechanical testing fail specifications.
- Escalate failures to quality assurance for root cause investigation and CAPA implementation.
Process Performance Qualification (PPQ) Batch Execution and Evaluation
- Execute a minimum of three consecutive PPQ batches under validated conditions using finalized CPPs and control strategies.
- During PPQ runs:
- Maintain detailed records of CPPs, in-process controls, and environmental conditions.
- Conduct full sampling and testing per the sampling plan.
- Document any deviations and evaluate their impact on backing membrane integrity.
- Analyze PPQ data for consistency and compliance with acceptance criteria including:
- Statistical analysis of defect rate trends to confirm process stability.
- Verification that all CPPs remained within specified ranges throughout the batch.
- Confirmation of product quality attributes related to membrane integrity.
- Prepare comprehensive validation reports including recommendations for ongoing monitoring or process improvements.
- Obtain quality assurance approval prior to commercial release.
Post-Validation Monitoring and Continuous Improvement
- Implement ongoing monitoring of CPPs and membrane integrity through routine in-process and final product testing.
- Analyze trending data for early detection of any deviation or drift.
- Review and update risk assessments periodically based on manufacturing experience and product complaints.
- Incorporate lessons learned from post-market feedback to refine control strategy or sampling plans.
- Maintain compliance with regulatory requirements for process validation lifecycle management.
Summary
Backing membrane integrity validation in transdermal patch manufacturing requires a systematic, risk-based approach encompassing FMEA, CPP identification, DoE, control strategy development, rigorous sampling and inspection, and thorough PPQ batch evaluation. By following these detailed steps, pharmaceutical professionals can establish robust validation protocols that ensure the protective backing membrane consistently meets quality standards, maintaining product efficacy and patient safety throughout its shelf life.
Design of Experiments (DoE) for Process Optimization
- Develop a factorial or response surface design focused on identified CPPs such as lamination pressure, temperature, and cutting speed.
- Include interaction effects between parameters to understand combined impact on membrane defects like tears or pinholes.
- Measure output variables related to membrane integrity, including tensile strength, puncture resistance, and visual defect rate.
- Analyze statistical significance of factors to establish robust operating ranges minimizing defects.
Establish Control Strategy and Acceptance Criteria
- Use risk assessment and DoE results to define critical quality attributes (CQAs) related to the backing membrane.
- Set acceptance limits for membrane integrity tests such as maximum allowable puncture defects, peel strength, and thickness uniformity.
- Implement in-process controls to monitor CPPs continuously, for example, real-time pressure sensors in lamination and automated blade condition checks.
- Apply Statistical Process Control (SPC) to detect deviations and trends that could indicate impending integrity failure.
Develop a Process Flow and Sampling Plan
- Map the complete manufacturing workflow highlighting process steps impacting membrane integrity, such as film extrusion, lamination, cutting, and packaging.
- Define sampling points at critical stages, for example, post-lamination and post-cutting, to verify membrane integrity attributes.
- Specify sample size and frequency based on batch size and risk assessment outcomes to ensure representative quality data collection.
- Document sampling procedures in the validation protocol to guarantee repeatability and compliance.
Protocol Design and Pre-Production Qualification (PPQ)
- Design a comprehensive validation protocol including objectives, scope, identified CPPs, CQAs, test methods, and acceptance criteria.
- Outline detailed batch manufacturing steps with specified process parameters and sampling points.
- Include data collection templates for real-time monitoring and final product testing.
- Execute at least three consecutive PPQ batches under defined operating conditions to demonstrate process reproducibility and membrane integrity consistency.
Execution, Monitoring, and Evaluation of Validation Batches
- Perform production runs adhering strictly to the protocol-defined CPPs and sampling strategies.
- Monitor real-time CPP data and membrane integrity tests during production.
- Document any deviations or anomalies, performing root cause analysis for any out-of-specification results.
- Analyze accumulated data statistically to confirm process stability, capability, and compliance with acceptance criteria.
- Compile a validation report summarizing findings, including FMEA updates, DoE conclusions, PPQ batch results, and control strategy effectiveness.
- Recommend ongoing monitoring post-validation to sustain membrane integrity assurance during commercial manufacturing.
Backing Membrane Integrity Validation in Transdermal Patches Manufacturing
All equipment used in this process validation must be duly qualified and validated for its intended use and performance specifications. Equipment qualification (IQ/OQ/PQ) is assumed to be completed prior to this process validation.
Preparation and Risk Assessment
Begin by reviewing the manufacturing process flow of the transdermal patches, focusing specifically on the backing membrane sealing and integrity checkpoints. Conduct a preliminary risk assessment to identify critical control points where backing membrane failure could compromise product quality and drug delivery performance. Use historical defect data, material specifications, and process parameters to prioritize critical parameters for validation.
Gather all applicable regulatory guidelines and internal standards for membrane seal integrity testing specific to transdermal patches. Ensure test methods selected can detect leaks, delamination, and membrane defects relevant to the transdermal dosage form.
Define Acceptance Criteria and Test Methods
Define quantitative and qualitative acceptance criteria for backing membrane integrity based on pharmacopeial standards, regulatory directives, and in-house quality benchmarks. Typical acceptance criteria include:
- Zero tolerance for visible leaks or delamination
- Passing results for standardized bubble emission, dye ingress, or electrical conductivity tests
- Relative standard deviation (RSD) thresholds for multiple batch comparison (commonly ≤ 10%)
Select test methods that provide high sensitivity and reproducibility for the backing membrane integrity detection. Recommended tests may comprise:
- Vacuum bubble test
- Dye penetration test
- Electrical conductivity or capacitance leak tests
- High voltage leak detection (HVLD)
Document the test procedures detailing sample size, test conditions, equipment calibration status, and evaluation criteria.
Conduct Process Performance Qualification (PPQ)
Perform validation runs on three consecutive batches to assess the consistency of backing membrane integrity. Each batch should be representative of commercial-scale manufacturing conditions.
- Collect samples randomly from different positions across the batch to ensure uniform testing coverage.
- Perform the selected membrane integrity tests within the predefined environmental and operational conditions.
- Record all raw data, observations, and deviations meticulously.
- Document operator details and equipment identifiers to ensure traceability.
Validation Result Tabulation
| Batch Number | Number of Samples Tested | Defects Found (No.) | Defect Type | Test Method Used | Pass/Fail | RSD (%) |
|---|---|---|---|---|---|---|
| Batch 001 | 50 | 0 | N/A | Vacuum Bubble Test | Pass | 3.2% |
| Batch 002 | 50 | 1 | Minor delamination | Dye Penetration Test | Pass* | 4.5% |
| Batch 003 | 50 | 0 | N/A | Vacuum Bubble Test | Pass | 3.8% |
*Batch 002’s minor delamination was investigated and deemed within acceptable process variation after review.
Comparative Summary Table for Membrane Integrity Across Batches
| Parameter | Batch 001 | Batch 002 | Batch 003 | Observations |
|---|---|---|---|---|
| Test Method | Vacuum Bubble | Dye Penetration | Vacuum Bubble | Test methods alternated based on batch but validated for equivalency. |
| Defect Rate (%) | 0% | 2% | 0% | Low defect incidence indicates consistent membrane sealing. |
| RSD | 3.2% | 4.5% | 3.8% | Within predefined acceptance limit (≤10%). |
| Compliance | Compliant | Compliant after investigation | Compliant | Validated membrane integrity achieved in all batches. |
Relative Standard Deviation and Compliance Analysis
Calculate the relative standard deviation (RSD) of defect detection results across the three batches for membrane integrity to evaluate process consistency:
- The maximum RSD observed (4.5%) remains well below the commonly accepted limit of 10%, demonstrating stable manufacturing performance.
- Compliance is confirmed by the absence or acceptable levels of membrane defects without adverse impact on patch performance.
- Analysis indicates the manufacturing process maintains integrity parameters within established limits, ensuring product quality robustness.
Continuous Process Verification and Routine Monitoring
Establish routine in-process and end-product monitoring for backing membrane integrity as part of ongoing process control:
- Define sample size and frequency based on initial validation findings and batch sizes (e.g., 1% of patches per batch tested using the standardized leak detection method).
- Record results in routine check sheets aligned with Good Manufacturing Practice (GMP) documentation standards.
- Implement alert limits to trigger immediate investigation if defect rates exceed validated thresholds.
- Use data trending tools to monitor long-term patterns in membrane integrity, identifying early signs of potential process drift.
Annual Product Quality Review (APQR) and Trending
Include backing membrane integrity data as a key component in the APQR documentation annually:
- Summarize all defect observations, process deviations, and corrective actions taken during routine monitoring.
- Analyze trends for statistically significant changes in defect rates or test failures using validated quality metrics software where applicable.
- Assess ongoing suitability of test methods and acceptance criteria in line with evolving regulatory guidance or process improvements.
- Recommend actions for enhancing process robustness or test sensitivity if justified by trending data.
Documentation and Annexures
Maintain comprehensive documentation as part of the process validation package. Prepare templates for uniform record-keeping, including:
- Annexure I: Backing Membrane Integrity Test Protocol Template – Outlines testing methodology, sample sizes, and acceptance criteria.
- Annexure II: Test Data Recording Sheet – Standardized form for capturing raw data and observations during membrane integrity testing.
- Annexure III: Defect Investigation Report Template – For documenting root cause analysis and corrective/preventive actions associated with membrane integrity failures.
- Annexure IV: Routine Monitoring Checklist – For ongoing in-process verification and documentation of integrity assessments.
- Annexure V: APQR Summary Form for Membrane Integrity – Structured format for annual review and trending analysis inclusion.
Ensure that all templates are version controlled and accessible to relevant manufacturing and quality assurance personnel. These documents form a critical part of GMP compliance and facilitate audits and inspections.
Conclusion
Backing membrane integrity validation for transdermal patch manufacturing is essential to guarantee dosage form effectiveness and patient safety. By following a structured stepwise approach—starting from preparation, through PPQ execution, data analysis, and routine monitoring, supplemented by detailed documentation—pharmaceutical professionals can achieve sustained process control and regulatory compliance. Thorough trending and APQR incorporation ensures that the membrane integrity remains robust throughout the product lifecycle.
Validation Result Tabulation and Analysis
| Batch No. | Sample Size | Number of Defects | Leak Test Method | Pass Rate (%) | RSD (%) | Compliance Status |
|---|---|---|---|---|---|---|
| Batch 001 | 50 | 0 | Vacuum Bubble Test | 100 | — | Pass |
| Batch 002 | 50 | 0 | Vacuum Bubble Test | 100 | — | Pass |
| Batch 003 | 50 | 1 | Vacuum Bubble Test | 98 | 1.02 | Pass |
Comparative Summary and Statistical Evaluation
| Parameter | Batch 001 | Batch 002 | Batch 003 | Average | RSD (%) | Compliance Status |
|---|---|---|---|---|---|---|
| Pass Rate (%) | 100 | 100 | 98 | 99.33 | 1.02 | Compliant (≤10% RSD) |
| Defect Count | 0 | 0 | 1 | 0.33 | — | Acceptable |
Interpret the results with emphasis on the relative standard deviation (RSD) and compliance against acceptance criteria. An RSD ≤ 10% confirms process consistency and robustness. Any anomalies must be investigated and justified or corrected before proceeding.
Continual Process Verification (CPV) and Routine Monitoring
- Establish a CPV protocol that incorporates routine backing membrane integrity testing during regular production runs.
- Define sampling plans, test frequency, and acceptance criteria consistent with validated process parameters.
- Integrate real-time data acquisition where feasible, allowing prompt identification of leaks or defects.
- Document all maintenance, calibration, and corrective actions in a dedicated logbook for traceability.
- Review process performance monthly or quarterly, applying statistical tools to detect trends and prevent drift.
Annual Product Quality Review (APQR) and Trending
- Aggregate membrane integrity data from routine testing and CPV for the annual quality review.
- Perform trend analysis on defect rates, pass/fail outcomes, and critical parameter variation.
- Highlight any deviations or excursions and initiate CAPAs where necessary.
- Review equipment qualification status and calibration records to support ongoing process validation compliance.
- Recommend process or material improvements based on trending outcomes to optimize product quality.
Annexures and Documentation Templates
Implement comprehensive record-keeping by using the following template annexures for consistency and audit readiness:
- Annexure I: Backing Membrane Integrity Test Procedure Template – includes step-by-step instructions and acceptance criteria.
- Annexure II: Process Performance Qualification (PPQ) Test Data Sheet – standardized format for recording individual batch test outcomes.
- Annexure III: Continual Process Verification Checklist – for routine monitoring activities and deviations management.
- Annexure IV: Annual Product Quality Review (APQR) Data Compilation Form – facilitates summary and trend analysis.
- Annexure V: Corrective and Preventive Action (CAPA) Report Template – documents root cause analysis and implementation of remedial steps.
Ensure all documentation is maintained in controlled systems adhering to Good Documentation Practices (GDP) and is readily accessible during audits and inspections.