Capsule: SOP for Encapsulation of Multi-Layer Pellets in Capsules – V 2.0

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Standard Operating Procedure for Encapsulation of Multi-Layer Pellets in Capsules

Department	Capsule Manufacturing
SOP No.	SOP/CM/097/2025
Supersedes	SOP/CM/097/2022
Page No.	Page 1 of 7
Issue Date	01/02/2025
Effective Date	05/02/2025
Review Date	01/02/2026

1. Purpose

The purpose of this SOP is to define the process for the encapsulation of multi-layer pellets into capsules. Multi-layer pellets are used for controlled, extended, or delayed drug release, and this procedure ensures proper encapsulation to maintain product integrity, efficacy, and compliance with regulatory standards.

2. Scope

This SOP applies to the encapsulation process of multi-layer pellets into capsules within the capsule manufacturing department. It covers the preparation of multi-layer pellets, the encapsulation process, and the quality checks necessary to ensure uniformity and compliance with product specifications.

3. Responsibilities

Production Operators: Responsible for the accurate preparation of multi-layer pellets and loading them into the encapsulation machine. They must follow the SOP precisely to ensure proper encapsulation.
Quality Control (QC) Team: Responsible for inspecting the finished capsules to ensure the proper encapsulation of multi-layer pellets and verifying the uniformity of the final product.
Quality Assurance (QA) Team: Ensures that the SOP is followed correctly, oversees the process for compliance with GMP, and approves the final encapsulated capsules.
Production Supervisor: Oversees the encapsulation process, ensures that the equipment is calibrated, and ensures that all steps are followed correctly.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the multi-layer pellet encapsulation process is carried out as per the SOP. The QA Manager is responsible for reviewing the encapsulation results and approving the final product for release.

5. Procedure

5.1 Preparing Multi-Layer Pellets for Encapsulation

Before beginning the encapsulation of multi-layer pellets, ensure that the following steps are completed:

Review the Pellet Formulation
1. Verify the pellet formulation for multi-layered pellets, ensuring that the appropriate layers are formulated for the desired release profile (e.g., immediate release, sustained release, or enteric coating).
2. Ensure that the pellets are within the required size range for encapsulation.
Prepare the Pellets
1. Prepare the multi-layer pellets by mixing the layers and ensuring uniform distribution of each layer’s active ingredients and excipients.
2. Ensure that the pellets are free from clumps, cracks, or other defects that could affect their performance during encapsulation.
Check Pellet Moisture Content
1. Ensure the pellets’ moisture content is within the acceptable range for encapsulation to prevent issues such as sticking or uneven encapsulation.
2. If necessary, adjust the moisture content by drying or humidifying the pellets to the required specification.

5.2 Encapsulation Process

Once the pellets are prepared, follow the procedure for encapsulation:

Set Up the Encapsulation Equipment
1. Set up the capsule filling machine according to the manufacturer’s instructions. Ensure that all settings, such as capsule size and fill weight, are properly configured for multi-layer pellets.
2. Ensure the filling machine is clean and calibrated, and check for any defects that could affect the encapsulation process.
Load Pellets into the Encapsulation Machine
1. Carefully load the multi-layer pellets into the capsule filling machine, ensuring that they are evenly distributed and that there is no material spillover.
2. Monitor the loading process to ensure that the correct amount of pellets is being encapsulated into each capsule.
Encapsulate the Pellets
1. Start the encapsulation process and ensure that each capsule is filled with the correct amount of multi-layer pellets.
2. Monitor the machine for any issues such as misalignment of capsules or uneven filling, and make adjustments as necessary to ensure uniformity.
Verify Capsule Integrity
1. Inspect the capsules for proper sealing and ensure that the multi-layer pellets are securely encapsulated inside the capsule shell.
2. Ensure there are no cracks or leaks in the capsule shell, which could result in the pellets being exposed to the external environment.

5.3 Quality Control and Inspection

Once the capsules are filled, perform the following quality control checks:

Visual Inspection
1. Inspect the encapsulated capsules visually for uniformity of shape, size, and weight. Ensure that the capsules are consistent and that the pellets are evenly distributed.
2. Check for any visible defects such as cracks, leaks, or improperly sealed capsules.
Weight and Fill Uniformity
1. Perform weight checks on a sample of capsules to ensure that the fill weight meets the specified target. The weight should be consistent across capsules.
2. If deviations from the target weight are found, investigate the cause and adjust the machine settings or pellet loading process as needed.
Pellet Distribution
1. Perform a cross-sectional examination of the filled capsules to ensure that the multi-layer pellets are distributed evenly within the capsule shell.

5.4 Documentation and Reporting

All activities related to the encapsulation of multi-layer pellets should be properly documented:

Maintain Batch Records
1. Ensure that all relevant details such as batch number, pellet formulation, encapsulation machine settings, and capsule weight are recorded in the Batch Production Record (BPR) (Annexure-1).
Record Deviations
1. If any deviations are observed during the encapsulation process (e.g., weight out of range, leakage, poor pellet distribution), they should be documented in the Deviation Log (Annexure-2) along with the corrective actions taken.

5.5 Final Approval and Packaging

Once the encapsulation process is complete, the following steps should be followed:

QA Review
1. The QA team should review the batch records, inspection results, and corrective actions taken to ensure that the encapsulation process meets the required standards.
Approval for Packaging
1. If the multi-layer capsules meet the required specifications, the batch is approved for packaging and labeling.

6. Abbreviations

SOP: Standard Operating Procedure
GMP: Good Manufacturing Practice
QC: Quality Control
QA: Quality Assurance
BPR: Batch Production Record

7. Documents

Batch Production Record (BPR) (Annexure-1)
Deviation Log (Annexure-2)
Capsule Inspection Log (Annexure-3)

8. References

USP <1163> – Pharmaceutical Dosage Forms: Capsules
FDA Guidelines for Capsule Manufacturing
Good Manufacturing Practice (GMP) Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

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	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Batch Production Record (BPR)

Batch ID	Pellet Formulation	Encapsulation Settings	Capsule Weight	Pellet Distribution	Deviation
Batch 001	Layer 1: API, Layer 2: Excipients	Encapsulator set at 200 mg per capsule	200 mg	Even distribution	No deviation

Annexure-2: Deviation Log

Deviation ID	Description	Corrective Action	Operator Name	Approval Status
DEV-001	Uneven capsule fill weight	Recalibrated the encapsulation machine and checked for pellet distribution	Jane Smith	Approved

Annexure-3: Capsule Inspection Log

Batch ID	Capsule Shape	Weight (mg)	Pellet Distribution	Operator Name	Inspection Outcome
Batch 001	Uniform shape	200 mg	Even	John Doe	Passed

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial Version	New SOP Creation	QA Head
01/02/2025	2.0	Updated encapsulation process and documentation requirements	Standardization	QA Head