4) Procedure

The following steps outline the procedure for using alternative models in preclinical studies:

1. Step 1: Identification and Selection of Alternative Models
   1. Identify the need for an alternative model based on the study objectives, such as reducing animal use or improving the relevance of the model to human biology.
   2. Select appropriate alternative models, which may include in vitro cell cultures, humanized animal models, computer simulations, or organ-on-a-chip technologies.
   3. Ensure that the chosen model is scientifically validated for the specific endpoint (e.g., cytotoxicity, absorption, metabolism, or toxicity) it is being used to assess.
2. Step 2: Validation of Alternative Models
   1. Ensure that the alternative model has been scientifically validated for the intended application, either through internal validation studies or external validation in peer-reviewed literature.
   2. Perform preliminary validation studies, comparing the alternative model’s results with traditional in vivo data or known clinical outcomes to confirm its predictive accuracy.
   3. Document the validation process, including methods, results, and any regulatory guidelines that are followed during the validation procedure.
3. Step 3: Study Design and Protocol Development
   1. Develop a study protocol that defines the alternative model to be used, the experimental conditions, and the endpoints to be evaluated.
   2. Ensure that the protocol aligns with regulatory guidelines and that the data generated from the alternative model will be suitable for further drug development phases, including clinical trials.
   3. Define quality control measures, including reproducibility, assay controls, and validation of reagents or equipment used in the alternative model.
4. Step 4: Conducting the Study
   1. Execute the study according to the protocol, ensuring that the conditions for the alternative model are maintained throughout the duration of the study.
   2. Monitor the model for any deviations or changes in behavior, data quality, or unexpected outcomes, and document any observations.
   3. If applicable, ensure that the alternative model is adjusted to human-relevant conditions, such as using human cell lines or humanized systems.
5. Step 5: Data Collection and Analysis
   1. Collect data from the alternative model, ensuring that it is consistently recorded and appropriately analyzed for accuracy and validity.
   2. Analyze the data using appropriate statistical methods, comparing it with historical data or control groups (e.g., from animal models or clinical outcomes) to determine the model’s predictive value.
   3. Interpret the results in the context of the overall study, considering both the advantages and limitations of using alternative models over traditional in vivo studies.
6. Step 6: Reporting and Documentation
   1. Prepare a comprehensive study report that includes a description of the alternative model, the study design, the results, and any conclusions about the efficacy or safety of the drug based on the model.
   2. Ensure that the report is scientifically sound, clearly written, and in compliance with internal protocols and regulatory requirements.
   3. Document any challenges or limitations encountered with the alternative model, along with suggestions for future improvements or alternative approaches if necessary.
7. Step 7: Archiving of Study Data
   1. Archive all raw data, reports, and documentation related to the alternative model study in a secure location in compliance with Good Laboratory Practice (GLP) standards.
   2. Ensure that the archived data is easily retrievable for future reference, audits, or regulatory reviews.
8. Step 8: Sample Disposal
   1. Dispose of all biological samples, chemicals, and laboratory waste following biosafety and waste disposal regulations.
   2. Ensure that all hazardous materials, including biological waste or reagents, are disposed of in designated biohazard or chemical waste containers.

5) Documents

The following documents should be maintained during the study using alternative models:

1. Study Protocols
2. Validation Reports
3. Raw Data Logs
4. Study Reports
5. Regulatory Submission Documents
6. Quality Control Logs
7. Animal Health and Welfare Logs (if applicable)
8. Deviations and Justifications
9. Waste Disposal Records

6) Abbreviations

• GLP: Good Laboratory Practices
• FDA: Food and Drug Administration
• QA: Quality Assurance
• IV: In Vitro
• OECD: Organisation for Economic Co-operation and Development

7) References

References to regulatory guidelines and scientific literature that support this SOP:

• OECD Guidelines for the Testing of Chemicals
• FDA Guidance on the Use of Alternative Methods in Toxicology
• ICH S7A and S7B Safety Pharmacology Guidelines
• Guidance on the Validation and Use of In Vitro Assays for Safety Testing

8) Version

Version 1.0: Initial version of the SOP.

9) Annexure

Alternative Model Validation Report Template