Granulation Uniformity Validation in Granules Manufacturing Processes
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 Granulation Uniformity Validation
Granulation uniformity validation is an essential component in the pharmaceutical manufacturing of granules, ensuring consistent product quality and reproducibility. This validation confirms the uniform distribution of active pharmaceutical ingredients (API) and excipients throughout the granules, which directly affects dosage form performance attributes such as content uniformity, dissolution, and stability. Successful validation ensures compliance with cGMP principles and regulatory expectations, forming part of a robust quality management system.
Granules manufacturing requires a carefully controlled granulation process—either wet granulation, dry granulation, or fluidized bed granulation—where parameters must be validated to produce homogeneous granulate batches that meet predetermined quality criteria. The validation of granulation uniformity focuses on demonstrating control over critical process variables that influence the uniformity and quality of granules.
Role of Granulation Uniformity Validation in cGMP and Quality Consistency
Per current Good Manufacturing Practices (cGMP), pharmaceutical manufacturers must establish and maintain documented evidence that the manufacturing process consistently produces granules meeting their predetermined specifications. Validation of granulation uniformity reduces risks of batch-to-batch variability, content variability, and potential manufacturing failures.
Key cGMP requirements necessitate:
- Verification of consistent granule content uniformity throughout the batch.
- Control of critical process parameters (CPPs) affecting granule uniformity.
- Evaluation and confirmation of process capability to reliably achieve quality target product profiles (QTPP).
By performing granulation uniformity validation, manufacturers demonstrate process robustness, supporting regulatory submissions and ongoing batch release quality assurance.
Defining the QTPP for Granules Manufacturing
The Quality Target Product Profile (QTPP) outlines the desired quality characteristics of the final granules, serving as a guiding framework throughout process validation. For granules, the QTPP includes attributes critical for downstream processing and drug product performance:
- Content uniformity: Homogeneous distribution of API across granules.
- Particle size distribution: Uniform granule size to ensure flowability and compressibility.
- Moisture content: Controlled to prevent degradation or compromised flow.
- Dissolution performance: Ensuring that granules meet release profile specifications.
- Flow properties: Adequate flow to avoid segregation or dosing errors.
These attributes must be quantifiably measured and controlled to meet the established QTPP in all batches.
Desired Attributes of Granule Uniformity
To achieve validation success, the granulation process must reliably produce granules with characteristics that fulfill predetermined acceptance criteria. Desired attributes include:
- Homogeneous API distribution: Verified through sample testing at multiple batch locations.
- Consistent granule size distribution: Avoiding excess fines or oversized particles.
- Controlled moisture content: Ensuring neither overdrying nor excessive residual moisture.
- Good flowability: Measured by angle of repose, Hausner ratio, or flow rate.
- Mechanical strength: Sufficient to withstand downstream handling without excessive friability.
Meeting these uniformity attributes directly supports the quality, stability, and efficacy of the final pharmaceutical product.
Impact of Granulation Uniformity on QTPP
Variability in granulation uniformity can negatively affect final product quality and therapeutic performance. Specific impacts include:
- Impaired content uniformity: Leading to dose inconsistencies and potentially sub-therapeutic or toxic doses.
- Variable dissolution rates: Affecting bioavailability and onset of action.
- Poor flow and compressibility: Resulting in manufacturing issues such as segregation, sticking, or weight variability in final dosage forms.
- Increased stability risks: Irregular moisture content can cause API degradation or physical instability.
Strict control and validation of granule uniformity mitigate these risks and ensure product robustness.
Critical Quality Attributes (CQAs) for Granule Uniformity
Identifying and monitoring CQAs relevant to granulation uniformity is a fundamental step. CQAs typically include:
- Granule assay and uniformity: API concentration across sampled granule portions.
- Particle size distribution (PSD): Typically determined by sieve analysis or laser diffraction.
- Residual moisture content: Using Karl Fischer titration or loss on drying (LOD).
- Bulk and tapped density: To assess flow and packing behavior.
- Flowability indices: Hausner ratio, Carr’s index, or angle of repose measurements.
- Friability and mechanical strength: For physical robustness during handling.
The acceptance criteria for each CQA should be based on scientific rationale, benchmarking, and regulatory guidelines.
Key Properties to Evaluate for Granulation Uniformity Validation
During validation, focus on systematic evaluation of key properties influencing granulation uniformity. Essential properties and associated methods include:
- Sample Collection Strategy: Develop a statistically valid sampling plan covering multiple locations within the batch (start, middle, end, and corners) to assess uniformity.
- Assay Testing: Measure API content via validated analytical methods (e.g., HPLC) for each sample to determine content uniformity across the granules.
- Particle Size Analysis: Perform sieve or laser diffraction analyses on collected samples to confirm consistent particle size distribution.
- Moisture Determination: Test residual moisture at different granule sample points using validated moisture analysis techniques.
- Flow Property Testing: Measure flow parameters like angle of repose and bulk/tapped density to evaluate uniform flow characteristics.
- Physical Inspection: Evaluate granules visually for cohesion, agglomeration, and color uniformity.
- Data Analysis: Use statistical tools to assess intra-batch and inter-batch variability. Demonstrate consistency within predefined acceptance criteria.
By comprehensively evaluating these properties during process validation runs, manufacturers can establish robust control strategies to ensure granulation uniformity aligns with QTPP objectives.
Conclusion and Next Steps
Granulation uniformity validation is a critical step in confirming that the manufacturing process consistently produces granules with the desired quality attributes. By following a structured validation plan focusing on CQAs, sampling strategies, and methodical testing, pharmaceutical manufacturers can ensure compliance with cGMP, minimize batch variability, and guarantee patient safety and efficacy. Subsequent steps include establishing ongoing monitoring and control mechanisms, process capability assessments, and continuous improvement initiatives supporting lifecycle management.
Granulation Uniformity Validation: Ensuring Consistency in Granules 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.
Defining the Quality Target Product Profile (QTPP) for Granules
The Quality Target Product Profile (QTPP) outlines the desired attributes and performance criteria for the final granule product. Establishing a clear QTPP is imperative to guide the granulation uniformity validation process. Key components typically include particle size distribution, moisture content, flow properties, content uniformity, and stability parameters. These define the target quality attributes that the manufacturing process must consistently achieve to ensure therapeutic efficacy and patient safety.
Desired Attributes of Uniform Granules
Uniform granules exhibit consistent physical characteristics that contribute to predictable downstream processing and dosage form performance. Desired attributes include:
- Consistent particle size and distribution to enhance flowability and prevent segregation.
- Homogeneous distribution of API and excipients throughout all granules.
- Optimal moisture level to maintain granule integrity without compromising stability.
- Robust mechanical strength to withstand compression or capsule filling forces.
Impact of Granulation Uniformity on QTPP
Granulation uniformity directly influences key QTPP parameters such as dosage uniformity, dissolution rate, and stability. Non-uniform granules can lead to variability in content uniformity, resulting in sub- or supra-therapeutic dosing in final dosage units. Additionally, irregular granule size distributions can affect powder flow, impacting tablet weight variation and capsule filling accuracy. Ensuring granule uniformity helps maintain batch-to-batch consistency, meeting both regulatory expectations and patient safety requirements.
Critical Quality Attributes (CQAs) Linked to Granulation Uniformity
CQAs are measurable properties that must be controlled to meet the desired quality outcomes of the granules. For granulation uniformity validation, critical attributes include:
- Content Uniformity: API concentration consistency throughout the granules.
- Particle Size Distribution: Ensuring target granule size range without excessive fines or oversized particles.
- Moisture Content: Maintaining water levels within limits to prevent degradation or hardening.
- Flow Properties: Evaluating parameters such as angle of repose and compressibility index for uniform filling and tablet compression.
- Granule Density and Porosity: Affecting dissolution and compression behavior.
Key Physicochemical Properties to Monitor During Validation
Monitoring vital properties during granulation uniformity validation provides critical data to confirm process control and product quality. These properties include:
- API Distribution Analysis: Techniques such as assay testing and near-infrared spectroscopy (NIR) help assess uniform API dispersion.
- Particle Size Analysis: Laser diffraction or sieve analysis to ensure consistent granule sizing.
- Moisture Determination: Karl Fischer titration or loss on drying to confirm moisture specifications.
- Flowability Testing: Measuring flow rate, angle of repose, and compressibility index to guarantee smooth manufacturing downstream.
- Bulk and Tapped Density: To evaluate packing and compaction characteristics.
Introduction to Granulation Uniformity Validation in Granules Manufacturing
Granulation uniformity validation is a critical aspect of process validation in granules manufacturing, ensuring consistent quality and performance of the dosage form. This validation confirms that the granulation process consistently produces granules with uniform properties, which is essential for dose accuracy, content uniformity, and downstream processing stability. Prior to execution, ensure all related equipment qualifications (IQ, OQ, PQ) have been satisfactorily completed to support reliable process validation.
Define the Validation Scope and Objectives
Begin by defining the scope of the granulation uniformity validation. Identify the specific granules product and manufacturing process to be validated. Determine key product attributes related to granulation uniformity such as particle size distribution, moisture content, density, and drug content uniformity. Establish the objectives to demonstrate that the granulation process consistently meets predefined specification limits.
Conduct Risk Assessment and FMEA
Perform a detailed Failure Modes and Effects Analysis (FMEA) focused on granulation uniformity. Follow these steps:
- Identify potential failure points in the granulation process that may cause non-uniformity, such as raw material variability, binder addition, mixing time, and equipment parameters.
- Assign severity ratings based on the impact of each failure mode on granule quality and patient safety.
- Assess the occurrence likelihood of each failure and its detectability by in-process controls or testing methods.
- Calculate Risk Priority Numbers (RPN) to prioritize critical control points requiring focused validation and monitoring.
- Document all findings and mitigation plans to address high-risk failure modes.
Select Critical Process Parameters (CPPs)
Identify the critical process parameters that influence granulation uniformity. Common CPPs include:
- Binder concentration and addition rate
- Granulation time and intensity (e.g., spray time, impeller speed)
- Moisture content during granulation
- Granulator feed rate and granule discharge rate
- Temperature and humidity conditions
Use historical data, risk assessment, and prior knowledge to justify CPP selection. These parameters will form the basis for process control and validation testing.
Design of Experiments (DoE) for Process Understanding
Implement a Design of Experiments to systematically study the effects of CPPs on granule uniformity attributes. Employ the following approach:
- Develop an experimental matrix covering selected CPP ranges.
- Conduct trials in a controlled environment, varying one or multiple CPPs according to the DoE plan.
- Collect data on granule particle size distribution, drug content uniformity, moisture content, and other relevant parameters.
- Analyze the results statistically to identify critical parameters and optimal process conditions promoting uniform granules.
- Use outcomes to refine CPP setting ranges and enhance the robustness of the granulation process.
Define Control Strategy and Acceptance Criteria
Establish a control strategy that ensures granulation uniformity throughout routine manufacturing:
- Set validated operating ranges for each CPP based on DoE and risk assessment results.
- Define in-process controls (IPCs) and monitoring methods such as real-time particle size analysis, moisture measurement, and binder flow rates.
- Develop sampling plans specifying sampling locations, frequency, and sample quantities aligned with GMP and regulatory expectations.
- Determine acceptance criteria for granule uniformity attributes according to pharmacopeial standards and product specifications—for example, the permissible coefficient of variation (CV) for assay uniformity or particle size parameters.
Process Flow and Sampling/Decision Points
Map the granulation process flow to identify critical sampling points where uniformity is assessed. A typical granulation process flow includes:
- Weighing and blending of raw materials
- Granulation mixing and binder addition
- Granule drying and cooling
- Granule sizing and classification
- Final blending
Sampling should be conducted at:
- End of granulation mixing to verify wet mass uniformity
- Post-drying, to check moisture level uniformity
- Post-sizing to confirm particle size distribution consistency
- At final blend stage to check content uniformity of granules
Samples must be representative and taken from multiple locations/batches to assess batch-to-batch and within-batch uniformity.
Design the Validation Protocol
Develop a comprehensive validation protocol that includes:
- Purpose and scope describing granulation uniformity focus
- List of equipment, materials, and personnel involved
- Detailed description of CPPs, control strategy, sampling plan, and analytical test methods
- Acceptance criteria for all measured attributes
- Outline of test batches (typically 3 consecutive PPQ batches) and rationale
- Data collection forms and reporting templates
- Contingency plans for out-of-specification results and corrective actions
The protocol must be approved by QA and controlled under document management systems.
Perform Process Performance Qualification (PPQ) Batches
Execute at least three consecutive PPQ batches under defined process conditions as specified in the protocol:
- Ensure all equipment is clean, calibrated, and ready.
- Run the granulation process using validated CPP settings within acceptable ranges.
- Conduct sampling at designated decision points following the protocol’s sampling plan.
- Analyze samples for uniformity parameters such as particle size distribution, drug content, moisture content, and any other critical quality attributes (CQAs).
- Document all process parameters and deviations meticulously.
Evaluate Batch Data and Document Results
Analyze the data obtained from PPQ batches to determine process capability and uniformity consistency:
- Compare measured values against accepted specification limits and control limits.
- Perform statistical evaluation on uniformity data including mean, standard deviation, and coefficient of variation (CV).
- Assess trend data for any indications of drift or variability outside control ranges.
- Verify that all CPPs were maintained within defined ranges throughout batch runs.
- Identify any out-of-specification or atypical results and initiate investigations if needed.
Summarize findings in a validation report with conclusions on process suitability for producing uniform granules.
Establish Ongoing Monitoring and Continuous Improvement
Once granulation uniformity validation is successfully completed, implement robust ongoing monitoring to maintain control and detect potential deviations early:
- Integrate IPCs and online monitoring tools to continuously track CPPs and CQAs during regular production.
- Schedule routine sampling per the approved control strategy and perform uniformity testing regularly.
- Use Statistical Process Control (SPC) charts to monitor trends and variation.
- Conduct periodic process revalidation or verification following changes in materials, equipment, scale, or process.
- Promote continuous improvement initiatives targeting reduction in variability and optimization of the granulation process.
Conclusion
Granulation uniformity validation is essential to guarantee the pharmaceutical quality attributes of granule-based dosage forms. By systematically assessing risks, defining CPPs, employing DoE, and executing structured PPQ batches with effective control strategies, manufacturing professionals can provide documented evidence of process consistency. Maintaining vigilant monitoring and control post-validation ensures ongoing compliance with regulatory requirements and delivers high-quality, uniform granule products to patients.
Granulation Uniformity Validation in Granules Manufacturing: Stepwise Process
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.
Define Validation Objectives and Acceptance Criteria
Begin by clearly establishing the objectives of granulation uniformity validation. The primary intent is to demonstrate that the granules produced consistently meet predefined uniformity specifications under routine manufacturing conditions.
- Identify critical quality attributes (CQAs) relevant to granule uniformity, including content uniformity, particle size distribution, moisture content, and API assay.
- Set acceptance criteria for each attribute based on regulatory guidelines and product specifications.
- Define the relative standard deviation (RSD) limits for granule uniformity, typically less than or equal to 5% RSD for content uniformity.
Selection of Batches for Validation
Choose representative commercial-scale batches for validation. A minimum of three consecutive batches should be selected to provide statistically significant evidence of uniformity.
- Ensure batches represent routine manufacturing conditions including raw material variability and process parameters.
- Document batch numbers, manufacturing dates, and any notable deviations in the validation protocol.
Sampling Plan Development
Develop a robust sampling plan to assess granulation uniformity throughout the batch.
- Define sampling points systematically during or after granulation (e.g., beginning, middle, end of batch discharge).
- Collect representative samples (minimum three samples per sampling point) to adequately reflect batch uniformity.
- Ensure that sampling is performed in compliance with Good Manufacturing Practices (GMP) to prevent cross-contamination or bias.
Analytical Testing for Uniformity
Perform the appropriate analytical tests on collected samples focusing on CQAs linked to uniformity.
- API Assay: Quantify active ingredient content using validated analytical methods (e.g., HPLC, UV spectrophotometry).
- Particle Size Distribution: Use sieving or laser diffraction techniques to confirm uniform granule size distribution across samples.
- Moisture Content: Assess residual moisture using techniques such as Karl Fischer titration or loss on drying.
- Physical Attributes: Assess flow properties or density if stipulated in the product specification.
Data Evaluation and Statistical Analysis
Analyze the data to confirm granule uniformity within and across batches.
- Calculate mean, standard deviation (SD), and relative standard deviation (RSD) for each tested attribute.
- Compare RSD values against predefined acceptance criteria; values ≤ 5% generally indicate acceptable uniformity.
- Construct comparative summary tables to present batch-to-batch consistency.
| Batch No. | Sampling Point | API Assay (%) Mean ± SD | RSD (%) | Particle Size Mean (µm) ± SD | Moisture Content (%) Mean ± SD | Compliance Status |
|---|---|---|---|---|---|---|
| Batch 1 | Start | 99.5 ± 0.8 | 0.8 | 350 ± 15 | 2.2 ± 0.1 | Pass |
| Batch 1 | Middle | 99.7 ± 0.7 | 0.7 | 355 ± 14 | 2.1 ± 0.2 | Pass |
| Batch 1 | End | 99.6 ± 0.6 | 0.6 | 348 ± 13 | 2.3 ± 0.1 | Pass |
| Batch 2 | Start | 99.4 ± 0.9 | 0.9 | 352 ± 16 | 2.2 ± 0.2 | Pass |
| Batch 2 | Middle | 99.8 ± 0.7 | 0.7 | 349 ± 13 | 2.1 ± 0.1 | Pass |
| Batch 2 | End | 99.6 ± 0.8 | 0.8 | 351 ± 14 | 2.3 ± 0.1 | Pass |
| Batch 3 | Start | 99.5 ± 0.6 | 0.6 | 353 ± 15 | 2.2 ± 0.1 | Pass |
| Batch 3 | Middle | 99.7 ± 0.7 | 0.7 | 350 ± 14 | 2.1 ± 0.1 | Pass |
| Batch 3 | End | 99.4 ± 0.9 | 0.9 | 349 ± 13 | 2.3 ± 0.2 | Pass |
Comparative Summary and Optimum Analysis
Construct a comparative summary table to facilitate visual review of granule uniformity performance across all three batches.
| Attribute | Batch 1 Mean ± RSD (%) | Batch 2 Mean ± RSD (%) | Batch 3 Mean ± RSD (%) | Acceptance Criteria | Compliance |
|---|---|---|---|---|---|
| API Assay (%) | 99.6 ± 0.7 | 99.6 ± 0.8 | 99.5 ± 0.7 | ±5% of label claim, RSD ≤ 5% | Pass |
| Particle Size (µm) | 351 ± 14 | 350 ± 14 | 351 ± 14 | Within specified range ±10% | Pass |
| Moisture Content (%) | 2.2 ± 0.1 | 2.2 ± 0.1 | 2.2 ± 0.1 | ≤3.0%, consistent across samples | Pass |
The low RSD values and consistency across batches indicate the granulation process maintains uniformity under routine manufacturing conditions and complies with acceptance criteria.
Documentation and Verification
Prepare comprehensive documentation encapsulating all facets of validation, including protocols, raw data, analysis, and conclusions.
- Complete the Continuous Process Verification (CPV) records to support ongoing validation status.
- Define routine monitoring plans (e.g., in-process checks, sampling frequency) post-validation to ensure sustained uniformity.
- Establish Annual Product Quality Review/Assessment (APQR/ARA) templates to incorporate granule uniformity trending data for long-term process robustness.
Annexure Templates for Documentation
Annexure I: Validation Protocol Template
- Objective, scope, and references
- Batch selection details
- Sampling plan and methodology
- Analytical methods used
- Acceptance criteria
- Responsibilities and timelines
Annexure II: Sampling Log Sheet
- Batch number and date
- Sampling points and times
- Sample ID and quantity collected
- Operator’s signature and observations
Annexure III: Analytical Results Recording Sheet
- Test method reference
- Sample ID and batch number
- Individual replicate results
- Calculated mean, SD, RSD
- Compliance status
Annexure IV: Comparative Analysis Summary Table
- Consolidated results across validation batches
- Statistical evaluation
- Conformance remarks
Annexure V: Continuous Process Verification (CPV) Plan Template
- Monitoring parameters and limits
- Sampling frequency
- Data review procedures
- Deviation management guidelines
Final Review and Approval
Circulate the final validation report and annexures for cross-departmental review, including Quality Assurance, Production, and Analytical teams.
- Incorporate comments and corrective actions, if any.
- Obtain formal approval signatures prior to implementation of routine manufacturing based on validated granulation uniformity.
Post-Validation Monitoring and Trending
Implement the documented CPV plan to continually verify granulation uniformity, ensuring early detection of drift or process deterioration.
- Collect routine monitoring data as per defined sampling strategy.
- Analyze data trends as part of APQR or quality reviews annually.
- Initiate investigations and corrective actions promptly for non-conformance or trend deviations.
Following these systematic instructions will ensure robust process validation for granulation uniformity in granules manufacturing, aligning with pharmaceutical regulatory expectations and guaranteeing consistent product quality.
Validation Result Tabulation
Consolidate the analytical test results for all sampled batches into a tabulated format for clear comparison and evaluation.
| Batch No. | Sampling Point | API Assay (%) | Particle Size (µm) | Moisture Content (%) | RSD (%) | Compliance Status |
|---|---|---|---|---|---|---|
| Batch 1 | Beginning | 99.5 | 350 | 2.1 | 3.2 | Pass |
| Batch 1 | Middle | 99.7 | 345 | 2.0 | 3.2 | Pass |
| Batch 1 | End | 99.4 | 348 | 2.2 | 3.2 | Pass |
| Batch 2 | Beginning | 99.6 | 352 | 2.0 | 3.5 | Pass |
| Batch 2 | Middle | 99.8 | 349 | 2.1 | 3.5 | Pass |
| Batch 2 | End | 99.5 | 351 | 2.1 | 3.5 | Pass |
| Batch 3 | Beginning | 99.7 | 347 | 2.0 | 3.1 | Pass |
| Batch 3 | Middle | 99.6 | 349 | 2.1 | 3.1 | Pass |
| Batch 3 | End | 99.5 | 350 | 2.2 | 3.1 | Pass |
Comparative Summary and Statistical Analysis
Perform a comprehensive comparative analysis using the tabulated validation results to understand uniformity trends and compliance relative to acceptance criteria.
- Calculate average values for each attribute across batches and sampling points.
- Compute the overall Relative Standard Deviation (RSD) to verify batch-to-batch consistency. RSD ≤ 5% indicates acceptable uniformity.
- Assess compliance by ensuring all measured values fall within predefined specification limits.
- Summarize findings in a comparative summary table to highlight any significant variations or trends.
| Attribute | Batch 1 Average | Batch 2 Average | Batch 3 Average | Overall Average | Overall RSD (%) | Acceptance Limit | Compliance |
|---|---|---|---|---|---|---|---|
| API Assay (%) | 99.5 | 99.6 | 99.6 | 99.57 | 0.11 | 98.0 – 102.0 | Pass |
| Particle Size (µm) | 347.7 | 350.7 | 348.7 | 349.0 | 0.43 | 330 – 370 | Pass |
| Moisture Content (%) | 2.1 | 2.07 | 2.1 | 2.09 | 0.92 | 1.5 – 3.0 | Pass |
Continued Process Verification (CPV) and Routine Monitoring
After successful process validation, maintain granule uniformity through continuous process verification and routine monitoring:
- Implement periodic sampling and testing of granules during routine production to detect trends or deviations early.
- Track process parameters and critical quality attributes in a control chart format with predefined alert and action limits.
- Ensure trending data are reviewed bi-annually or as per quality management schedule to confirm the process remains in a state of control.
- Review deviations and out-of-specification events promptly, initiating root cause analysis and corrective actions.
Annual Product Quality Review (APQR) and Trending
Integrate granulation uniformity data into the Annual Product Quality Review process:
- Compile CPV data along with batch release results and any deviations related to granule uniformity.
- Analyze trends over the year for shifts or drifts in granulation uniformity that could impact product quality.
- Recommend continuous improvement initiatives based on trend analysis to optimize manufacturing consistency.
- Document APQR findings and actions as part of the product lifecycle and regulatory compliance responsibilities.
Annexures: Validation Documentation Templates
Use the following annexure templates to ensure comprehensive documentation of granulation uniformity validation and ongoing quality assurance.
Annexure I: Validation Protocol Template
- Objective and scope
- Batch selection and sampling plan
- Test methods and acceptance criteria
- Responsibilities and timelines
Annexure II: Sampling Record Template
- Batch number and manufacturing date
- Sampling points and times
- Sample identification and handling details
Annexure III: Analytical Test Result Sheet Template
- Sample IDs with corresponding test results
- RSD calculations
- Pass/fail status for each attribute
Annexure IV: Validation Summary Report Template
- Summary of results with tables and graphs
- Statistical analysis and conclusions
- Deviations and corrective actions taken
Annexure V: Continued Process Verification Plan Template
- Monitoring points and frequencies
- Control limits and alert criteria
- Data review schedules and responsible personnel