Standard Operating Procedure for Formulating High-Potency Drugs in Capsules

Department	Capsule Manufacturing
SOP No.	SOP/CM/044/2025
Supersedes	SOP/CM/044/2022
Page No.	Page 1 of 6
Issue Date	01/02/2025
Effective Date	05/02/2025
Review Date	01/02/2026

1. Purpose

The purpose of this SOP is to establish a consistent procedure for formulating high-potency drugs in capsules. High-potency drugs require special handling and formulation techniques due to their small therapeutic dose and potential risk to personnel during production.

2. Scope

This SOP applies to the formulation of high-potency drugs in capsule dosage forms. It includes formulation design, process controls, and safety procedures required to handle and manufacture capsules containing high-potency active pharmaceutical ingredients (APIs).

3. Responsibilities

• Formulation Development Team: Responsible for developing and optimizing the formulation of high-potency drugs, including selecting excipients and establishing the desired drug release profile.
• Manufacturing Team: Responsible for the actual production of high-potency capsules, ensuring the correct encapsulation and uniformity of the formulation.
• Quality Control (QC) Team: Responsible for verifying the quality of the capsules, including testing for content uniformity, dissolution, and potential contamination.
• Quality Assurance (QA) Team: Ensures that all activities related to the formulation and manufacture of high-potency capsules comply with GMP standards and regulatory requirements.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the formulation process for high-potency drugs is conducted as per this SOP. The QA Manager is responsible for reviewing the process and ensuring compliance with quality and regulatory standards.

5. Procedure

5.1 Design of High-Potency Capsule Formulation

When formulating high-potency drugs, the following factors must be considered:

1. Determine API Dosage
   1. Identify the therapeutic dose of the API, ensuring that the encapsulated dose is accurate and uniform for patient safety.
2. Excipients Selection
   1. Select excipients that are compatible with the high-potency API, ensuring that they do not affect the drug’s stability or bioavailability.
   2. Common excipients include binders, fillers, disintegrants, and lubricants, all of which should be used in small quantities to minimize exposure to the drug.
3. Matrix Design
   1. If extended-release formulations are required, design a matrix system to control the release of the high-potency drug over time, ensuring uniform dosing throughout the treatment period.
4. Handling and Dose Uniformity
   1. Ensure that the dose of the high-potency drug is evenly distributed in the formulation to achieve consistent content in each capsule.
   2. Implement controls to ensure the uniformity of the dose and prevent overexposure to personnel during formulation and production.

5.2 Safety Precautions for High-Potency Drug Handling

High-potency drugs require special precautions to prevent contamination or exposure to personnel:

1. Containment
   1. Use closed-system containment equipment such as isolators or containment hoods to prevent the release of high-potency dust or particles into the work environment.
2. Personal Protective Equipment (PPE)
   1. Ensure all personnel involved in handling high-potency drugs wear appropriate PPE, including gloves, masks, and protective clothing, to minimize exposure.
3. Material Handling
   1. Use dedicated equipment for the handling of high-potency materials to prevent cross-contamination with other products. Clean equipment thoroughly after each use.

5.3 Capsule Filling and Encapsulation

Once the formulation is ready, the following steps should be followed during the encapsulation process:

1. Pre-fill Operations
   1. Prepare the encapsulation machine by ensuring it is properly cleaned and calibrated to handle the specific capsule size and fill weight for high-potency drugs.
   2. Ensure that the high-potency API is blended thoroughly with the excipients to achieve uniform distribution of the drug throughout the formulation.
2. Encapsulation
   1. Fill the prepared blend into capsules using automated capsule filling machines, ensuring that the fill weight is accurate and consistent.
   2. Monitor the filling process closely to prevent overfilling or underfilling, which could lead to dosage inaccuracies.
3. Quality Control Checks
   1. Perform visual inspections and weight checks to ensure the capsules are properly filled and sealed.
   2. Conduct content uniformity testing on a sample of capsules to confirm that the API is distributed evenly within each capsule.

5.4 Testing for Stability and Bioavailability

To ensure that the high-potency capsules meet all necessary specifications, perform the following tests:

1. Dissolution Testing
   1. Conduct dissolution tests to assess the release profile of the high-potency drug. The release rate should be consistent with the intended therapeutic profile of the formulation.
2. Stability Testing
   1. Conduct stability studies under various environmental conditions, such as temperature and humidity, to assess the long-term stability of the capsules and ensure that the drug maintains its potency.
3. Bioavailability Studies
   1. If applicable, perform bioavailability studies to confirm that the API in the high-potency capsule is absorbed in a manner that provides the intended therapeutic effect.

5.5 Documentation and Record-Keeping

Document all steps in the formulation and production of high-potency capsules:

1. Formulation Records
   1. Document the composition of the high-potency formulation, including the quantity of API, excipients, and any other ingredients used in the capsule.
2. Manufacturing Records
   1. Record the encapsulation process, including batch numbers, capsule size, and any adjustments made to the machine settings during the filling process.
3. Quality Control Records
   1. Maintain records of quality control testing, including content uniformity, dissolution testing, and stability studies.
4. Trial Reports
   1. Prepare a detailed trial report summarizing the development process, testing results, and any modifications made to the formulation or process.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• QC: Quality Control
• API: Active Pharmaceutical Ingredient
• GMP: Good Manufacturing Practice
• USP: United States Pharmacopeia

7. Documents

1. High-Potency Drug Formulation Record (Annexure-1)
2. Capsule Production Batch Record (Annexure-2)
3. Content Uniformity Testing Report (Annexure-3)

8. References

• USP <711> – Dissolution Testing
• FDA Guidance for Industry: Stability Testing of Drug Products
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Development

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: High-Potency Drug Formulation Record

Material	Weight	Function
High-Potency API	50 mg	Active Pharmaceutical Ingredient
Excipients	150 mg	Binder, Filler

Annexure-2: Capsule Production Batch Record

Batch ID	Encapsulation Parameters	Capsule Size	Machine Settings
Batch 001	Speed: 100 rpm	Size 0	Force: 15 N

Annexure-3: Content Uniformity Testing Report

Test Type	Result	Specification	Remarks
Content Uniformity	Pass	±10% of target dose	Uniform distribution

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 parameters	Standardization	QA Head