4) Procedure

The following steps outline the procedure for preparing preclinical dossiers for regulatory submissions:

1. Step 1: Data Collection and Organization
   1. Collect all relevant preclinical study data, including pharmacokinetics, toxicology, pharmacodynamics, and efficacy studies.
   2. Ensure that data from all stages of preclinical development are included, from early-stage safety and pharmacokinetics to late-stage efficacy studies.
   3. Organize the data into sections that align with the regulatory guidelines for the specific submission (e.g., IND, NDA, CTD). Each section should be clearly labeled and include all relevant information.
2. Step 2: Review and Verification of Data
   1. Ensure that all preclinical study reports are complete, accurate, and up-to-date. Review raw data, study protocols, and final study reports for consistency and compliance with regulatory standards.
   2. Verify the accuracy of key data points, including pharmacokinetic parameters, toxicity profiles, and efficacy endpoints. Ensure that any deviations from the study protocol are documented and justified.
   3. Ensure that all data has been obtained using validated methods that comply with Good Laboratory Practice (GLP) standards, and that any clinical observations or adverse reactions are clearly documented.
3. Step 3: Regulatory Guidelines Compliance
   1. Ensure that the preclinical dossier complies with the specific regulatory requirements of the authority to which it will be submitted (e.g., FDA, EMA, ICH, or local regulatory agencies).
   2. Review the guidelines for the regulatory submission type (e.g., IND, NDA) to ensure that the dossier includes all required data and sections, including toxicology studies, pharmacokinetics, and efficacy results.
   3. Ensure that the dossier format adheres to the submission standards, including section numbering, table formatting, and referencing.
4. Step 4: Dossier Compilation
   1. Compile the preclinical study data into a cohesive dossier, following the required regulatory format (e.g., CTD format, FDA guidelines).
   2. Ensure that each section of the dossier includes a summary of the study design, methodology, results, and conclusions. Include relevant data visualizations (e.g., graphs, tables) to illustrate key findings.
   3. Include a summary of the pharmacokinetic profile, including absorption, distribution, metabolism, and excretion (ADME), as well as safety data, including dose-response relationships, toxicity data, and any observed adverse effects.
   4. Ensure that efficacy data, including preclinical model results, are clearly presented and provide a scientific rationale for the drug’s potential in clinical trials.
5. Step 5: Review and Finalization
   1. Review the preclinical dossier for completeness, accuracy, and clarity. Ensure that all sections are properly organized and that the data is presented in a logical, accessible format.
   2. Ensure that all required documentation (e.g., ethics approval, GLP compliance certificates) is included in the dossier and that references are properly cited.
   3. Have the dossier reviewed by senior scientific staff and regulatory affairs specialists to ensure that all necessary information is included and that the dossier meets regulatory standards.
6. Step 6: Quality Assurance and Compliance Check
   1. Submit the preclinical dossier to the QA team for final review. The QA team will verify that the dossier meets GLP standards and complies with regulatory requirements.
   2. Ensure that any discrepancies or issues identified during the QA review are addressed before finalizing the dossier.
7. Step 7: Submission to Regulatory Authorities
   1. Submit the finalized preclinical dossier to the relevant regulatory authorities (e.g., FDA, EMA) following the required submission procedures and deadlines.
   2. Ensure that all required forms, certifications, and supporting documents are included in the submission package.
   3. Track the submission process and respond to any additional requests for information or clarification from the regulatory authorities.
8. Step 8: Archiving of Study Data
   1. Archive all preclinical data, study reports, and dossier documents in a secure and accessible location according to internal data retention policies.
   2. Ensure that the archived documents can be easily retrieved for future audits, regulatory reviews, or updates to the dossier.
9. Step 9: Sample Disposal
   1. Ensure that all biological samples, chemicals, and laboratory waste are disposed of in accordance with biosafety and waste disposal regulations.
   2. Dispose of any hazardous materials in designated biohazard or chemical waste containers to minimize environmental impact.

5) Documents

The following documents should be maintained during the preclinical dossier preparation process:

1. Study Protocols
2. Preclinical Study Reports
3. Data Analysis and Statistical Reports
4. Regulatory Submission Forms
5. Pharmacokinetic and Toxicology Data
6. Supporting Documentation (e.g., GLP compliance certificates, ethical approval)
7. Submission Confirmation Logs

6) Abbreviations

• GLP: Good Laboratory Practices
• FDA: Food and Drug Administration
• EMA: European Medicines Agency
• IND: Investigational New Drug
• NDA: New Drug Application
• CTD: Common Technical Document
• QA: Quality Assurance

7) References

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

• FDA Guidelines for Preclinical Safety Testing
• EMA Guidelines for Clinical Trial Applications
• ICH Guidelines for the Preparation of Regulatory Submissions
• OECD Principles of Good Laboratory Practice (GLP)

8) Version

Version 1.0: Initial version of the SOP.

9) Annexure

Preclinical Dossier Template