Process validation of Coated tablets and capsules. It includes types and stages of validation

1. Raghavendra Institute of Pharmaceutical Education and Research – Autonomous
K.R. Palli Cross, Chiyyedu, Anantapuramu, A.P. -515721
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S.LIKHITHA
24L81S0707
DEPARTMENT OF PHARMACEUTICAL ANALYSIS
PROCESS VALIDATION OF COATED
TABLETS AND CAPSULES
Under the guidance of
Dr. K. Vinod Kumar Mpharm,PhD
Associate professor
Department of Pharmaceutical Analysis

2. Raghavendra Institute of Pharmaceutical Education and Research – Autonomous
K.R. Palli Cross, Chiyyedu, Anantapuramu, A.P. -515721
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CONTENTS
Introduction
Types of Validation
General stages of Process validation
Process Design
Process Qualification
Continued Process Verification
Revalidation

3. Raghavendra Institute of Pharmaceutical Education and Research – Autonomous
K.R. Palli Cross, Chiyyedu, Anantapuramu, A.P. -515721
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INTRODUCTION
Process Validation of Coated Tablets and Capsules
Process validation is a critical component of pharmaceutical manufacturing that
ensures the process consistently produces a product meeting its predetermined
specifications and quality attributes. For coated tablets and capsules, validation
ensures not only the core formulation integrity but also the functionality, uniformity,
and stability of the coating or capsule shell.

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K.R. Palli Cross, Chiyyedu, Anantapuramu, A.P. -515721
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Types of validation
 Prospective Validation – Conducted before the product is released to ensure
the process performs as expected.
 Concurrent Validation – Performed during actual production to monitor and
validate the process in real-time.
 Retrospective Validation – Based on historical data from past production
batches to confirm process consistency.
 Revalidation – Repeating validation after changes in process, equipment, or
periodic review to maintain assurance.

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K.R. Palli Cross, Chiyyedu, Anantapuramu, A.P. -515721
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General Stages of Process Validation
According to FDA and ICH Q8-Q10 guidelines, validation is performed in
three stages:
1. Process Design
2. Process Qualification
3. Continued Process Verification

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K.R. Palli Cross, Chiyyedu, Anantapuramu, A.P. -515721
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1. Process Design (Development Phase)
Objective: Establish a robust manufacturing process through R&D and lab/pilot-scale
studies.
Activities:
 Identify critical quality attributes (CQAs):
e.g., weight
hardness
disintegration
dissolution,
appearance.
 Identify critical process parameters (CPPs): e.g., spray rate, pan speed, inlet
temperature (for coating), capsule fill weight, and tamping pressure.
 Perform risk assessments (e.g., FMEA).
 Define design space for tablet compression or capsule filling and coating processes.

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2. Process Qualification (Validation Batches)
Includes Equipment Qualification and Performance Qualification (PQ):
a. Equipment Qualification
IQ/OQ/PQ for key machines:
Tablet press
Coating pan (or fluid bed coater)
Capsule filling machine
Mixing and granulation equipment
Calibration of instruments (e.g., spray guns, temperature probes)
 Equipment Qualification includes
Installation Qualification (IQ): Verifies equipment installation as per
design specs
Operational Qualification (OQ): Tests equipment functionality within
define parameters
Performance Qualification (PQ): Verifies equipment performance during
actual production

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b. Performance Qualification
• Conduct at least 3 consecutive commercial-scale batches.
• Evaluate batch-to-batch consistency in:
Weight variation
Coating uniformity (e.g., thickness, color)
Dissolution profile
Content uniformity (assay)
Disintegration time
• Sampling should cover:
Beginning, middle, and end of the batch (for coating or filling)
Intra- and inter-batch variability
• Data analysis to confirm the process is under control and reproducible.

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Step Parameters to Validate Tests/Checks
Blending
Time, speed, type of
blender
Content uniformity
Granulation
Binder addition rate, time,
drying
Moisture content, particle
size
Compression
Hardness, weight,
thickness
In-process testing
Coating
Spray rate, air
temperature, pan speed,
weight gain
Uniformity, appearance,
dissolution
Packing
Tablet count, labeling,
seal integrity
Stability, traceability
For coated tablets

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Step Parameters to Validate Tests/Checks
Blending Uniformity, blend time Content uniformity
Capsule Filling Fill weight, compression Dosage accuracy
Shell Check
Cracks, brittleness,
defects
Visual inspection
Moisture Moisture of shell and fill Stability
Sealing (liquid)
Banding/sealing
efficiency
Leak test
For capsules

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 Sampling Plan:
Stratified sampling from the beginning, middle, and end of the batch
In-process sampling and finished product testing
Environmental monitoring (if an aseptic or critical area)
🔹 Tests Performed:
Content uniformity
Dissolution
Disintegration
Coating thickness/uniformity (weight gain%)
Appearance & surface defects
Hardness/Friability (for tablets)
Moisture content (for capsules)

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3. Continued Process Verification (Stage 3)
Ensures ongoing control and consistency after commercial launch.
🔹 Activities:
Trending of CPPs and CQAs via SPC (Statistical Process Control)
Batch release data analysis: Uniformity, dissolution, weight variation trends
Annual Product Review (APR) or Product Quality Review (PQR)
Deviation and CAPA monitoring
 Revalidation in case of:
Change in equipment, scale, site
Major change in raw materials
Regulatory requirement or observed trend deviation

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BENEFITS OF CPV
 Ensures product quality throughout the lifecycle
 Reduces product recall risks
 Supports QbD (Quality by Design) and PAT
 Enables real-time release testing (RTRT)
 Provides data for regulatory inspections/audits
 Facilitates continuous improvement (ICH Q10)

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✅ SUMMARY CHECKLIST
Item Tablet Coating Capsule Filling
Equipment IQ/OQ/PQ ✔️ ✔️
CQA & CPP
Identification
✔️ ✔️
3 Validation Batches ✔️ ✔️
Analytical Method
Validation
✔️ ✔️
Stability Samples ✔️ ✔️
Deviation Handling ✔️ ✔️
Final Report Approval by
QA
✔️ ✔️

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K.R. Palli Cross, Chiyyedu, Anantapuramu, A.P. -515721
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DOCUMENTATION REQUIRED
 CPV Plan/Protocol
 Monthly/Quarterly CPV Reports
 Deviations/OOS/OOT investigations
 CAPA Reports (if any)
 Statistical data and trend analysis
 Updates to risk assessments (FMEA)
 Annual Product Review (APR/PQR) inclusion

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K.R. Palli Cross, Chiyyedu, Anantapuramu, A.P. -515721
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REGULATORY GUIDELINES REFERRED
 U.S. Food and Drug Administration. Guidance for Industry: Process
Validation – General Principles and Practices. Silver Spring (MD): FDA;
2011.
 International Conference on Harmonisation (ICH). ICH Harmonised
Tripartite Guidelines Q8(R2), Q9, Q10: Pharmaceutical Development,
Quality Risk Management, Pharmaceutical Quality System. Geneva: ICH;
2009.
 World Health Organization. Annex 2: Validation. In: WHO Technical Report
Series No. 986. Geneva: WHO; 2014.
 European Commission. EU Guidelines for Good Manufacturing Practice
for Medicinal Products for Human and Veterinary Use: Annex 15 –
Qualification and Validation. Brussels: European Medicines Agency; 2015.

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