Document ID: SOP-MFG-001 (Example)

Revision Number: 01 (Example)

Effective Date: 2024-03-22 (Example)

Author: [Your Name/Department – e.g., Process Development]

Approver: [QA/Manufacturing Department]

1.0 Purpose

This Standard Operating Procedure (SOP) outlines the procedures for conducting in-house trials (also known as pilot trials, scale-up studies, or engineering runs) within [Organization Name/Pharmaceutical Manufacturing Firm]. In-house trials are small-scale experiments or manufacturing runs conducted prior to full-scale production. Their purpose is to evaluate various aspects of a proposed manufacturing process, including process feasibility, equipment suitability, raw material compatibility, process parameter optimization, and product quality attributes. This SOP aims to ensure that all in-house trials are conducted scientifically, safely, and in compliance with applicable regulations and internal quality standards.

2.0 Scope

This SOP applies to all personnel involved in the planning, execution, analysis, and reporting of in-house trials within the manufacturing division of [Organization Name/Pharmaceutical Manufacturing Firm]. This includes, but is not limited to, process development scientists, manufacturing engineers, operators, quality control personnel, and validation specialists. This SOP covers all in-house trials related to the manufacturing of pharmaceutical products, including new product development, process improvements, and scale-up activities.

3.0 Definitions

• In-House Trial (Pilot Trial/Scale-Up Study/Engineering Run): A small-scale experiment or manufacturing run conducted prior to full-scale production to evaluate the feasibility and optimize various aspects of a proposed manufacturing process.
• Master Formula Record (MFR): A document that specifies all the materials, components, and manufacturing instructions for a specific product.
• Batch Manufacturing Record (BMR): A document that provides a history of the manufacturing of a specific batch of product.
• Process Parameters: Specific variables that can influence the outcome of a manufacturing process (e.g., temperature, pressure, mixing speed).
• Critical Process Parameters (CPPs): Process parameters that have a significant impact on product quality.
• Critical Quality Attributes (CQAs): Physical, chemical, biological, or microbiological properties or characteristics that should be within an appropriate¹ limit, range, or distribution to ensure the desired product quality.²
• Scale-Up: The process of transferring a manufacturing process from a small-scale (e.g., laboratory or pilot scale) to a larger scale (e.g., pilot plant or production scale).
• Validation: The process of providing documented evidence that a specific process will consistently produce a product meeting its predetermined specifications³ and quality attributes.⁴

4.0 Responsibilities

• Trial Lead: The individual responsible for the overall planning, execution, and reporting of the in-house trial.
• Trial Team: Includes all personnel involved in the trial, responsible for performing their assigned tasks according to the protocol and this SOP.
• Process Development/Engineering Department: Responsible for designing and overseeing the in-house trials.
• Manufacturing Department: Responsible for executing the in-house trials in the manufacturing facility.
• Quality Assurance (QA) Department: Responsible for reviewing and approving the trial protocol, data, and report, ensuring compliance with GMP and this SOP.

5.0 Procedure

5.1 Trial Planning and Design:

1. Justification: The Trial Lead must provide a clear scientific and business justification for conducting the in-house trial. This justification should outline the specific objectives of the trial and how it will contribute to the development or improvement of the manufacturing process.

2. Protocol Development: A detailed protocol must be developed for each in-house trial. The protocol should include the following sections:

   • Background: A summary of the existing knowledge relevant to the manufacturing process.
   • Objectives: Clearly stated objectives of the trial, including specific process parameters to be investigated and CQAs to be evaluated.
   • Trial Design: Description of the trial design, including the scale of the trial (e.g., laboratory, pilot plant), equipment to be used, raw materials to be tested, and experimental design (e.g., factorial design, optimization study).
   • Process Parameters: Identification of CPPs and their acceptable ranges.
   • CQAs: Identification of CQAs and their target specifications.
   • Sampling Plan: Description of the sampling procedures to be used during the trial.
   • Analytical Methods: Description of the analytical methods to be used to evaluate CQAs.
   • Data Collection and Management: Procedures for collecting, storing, and managing trial data.
   • Statistical Considerations: Description of the statistical methods to be used for data analysis.
   • Safety Considerations: Description of the safety procedures to be followed during the trial.
   • Waste Disposal: Procedures for handling and disposing of waste generated during the trial.

3. Material Procurement: Ensure that all necessary raw materials, components, and equipment are available before the trial begins. Materials should be properly labeled, stored, and controlled.

4. Equipment Preparation: Ensure that all equipment to be used in the trial is calibrated, qualified, and in good working order. Maintenance records should be reviewed.

5. Safety Assessment: Conduct a thorough safety assessment to identify and mitigate any potential hazards associated with the trial. This may involve a risk assessment and the development of safety procedures.

6. QA Review and Approval: The trial protocol and related documents must be reviewed and approved by the QA department before the trial can begin.

5.2 Trial Execution:

1. Operator Training: All personnel involved in the trial must receive appropriate training on the protocol, SOPs, and safety procedures.

2. Batch Record Preparation: A batch record (or equivalent documentation) should be prepared for each trial run, detailing the manufacturing steps, process parameters, and materials used.

3. Process Execution: Execute the trial according to the protocol and batch record. Document all deviations from the protocol in the batch record.

4. Sampling and Testing: Collect samples according to the sampling plan and test them using the specified analytical methods. Record all test results in the batch record.

5. Data Collection: Collect all relevant data during the trial, including process parameters, CQAs, and any observations.

6. Deviation Management: Any deviations from the protocol or SOPs must be documented, investigated, and approved by the appropriate personnel.

7. Safety Monitoring: Monitor the trial for any safety incidents and take appropriate action if necessary.

5.3 Data Analysis and Reporting:

1. Data Analysis: Analyze the data collected during the trial according to the statistical analysis plan described in the protocol.

2. Trial Report: Prepare a written report summarizing the trial results. The report should include the following sections:

   • Summary: A brief overview of the trial.
   • Background: A summary of the existing knowledge relevant to the manufacturing process.
   • Objectives: Clearly stated objectives of the trial.
   • Trial Design: Description of the trial design.
   • Results: Presentation of the trial results, including tables and figures.
   • Discussion: Interpretation of the trial results and their implications for the manufacturing process.
   • Conclusion: Summary of the key findings of the trial and recommendations for future work.

3. QA Review and Approval: The trial report must be reviewed and approved by the QA department.

4. Documentation: All trial documents, including the protocol, batch records, test results, and report, should be stored securely and confidentially.

6.0 Documentation

The following documents should be maintained for each in-house trial:

• Trial protocol
• Batch records
• Test results
• Deviation reports
• Trial report
• Equipment calibration and qualification records
• Material certificates of analysis

All trial documents should be stored securely and confidentially according to document control procedures.

7.0 Quality Control

• The QA department will conduct regular audits of in-house trials to ensure compliance with this SOP and applicable regulations.
• Any deviations from this SOP should be documented and investigated. Corrective and preventive actions (CAPA) should be implemented to prevent future occurrences.

8.0 Safety Precautions

• All personnel involved in the trial must receive appropriate training on safety procedures, including handling of chemicals, operation of equipment, and emergency response.
• Appropriate personal protective equipment (PPE) must be worn during the trial.
• A risk assessment should be conducted before the trial to identify and mitigate potential hazards.

9.0 Waste Management

Waste generated during the trial should be handled and disposed of according to applicable environmental regulations and internal procedures.

10.0 Revision History

11.0 Scale-Up Considerations (If Applicable)

If the in-house trial is intended to support scale-up activities, the protocol should address the following: