Standard Operating Procedure for Review of Regulatory Guidelines before Study Start in BA/BE Studies

1. Purpose

To define the procedure for reviewing and aligning with current regulatory guidelines before the initiation of Bioavailability/Bioequivalence (BA/BE) studies to ensure protocol design, conduct, and reporting are compliant with applicable global regulations.

2. Scope

This SOP applies to all BA/BE studies conducted or submitted for approval to regulatory agencies including CDSCO (India), US FDA, EMA, Health Canada, TGA, PMDA, WHO, and others. It includes the pre-study assessment of national and international regulatory requirements, guidance documents, and updates.

3. Responsibilities

• Regulatory Affairs: Conducts regulatory intelligence review, compiles applicable guidelines, and ensures documentation of their implementation.
• Clinical Project Manager: Aligns protocol, ICF, and submissions with reviewed regulatory expectations.
• Quality Assurance: Verifies that regulatory requirements are documented during audits.

4. Accountability

The Head of Regulatory Affairs is accountable for ensuring that the most current and relevant regulatory guidelines are reviewed, documented, and applied before any BA/BE study is initiated.

5. Procedure

5.1 Regulatory Landscape Review

1. Initiate regulatory review during the protocol development stage or at least 4 weeks prior to site initiation.
2. Access the latest guidance from:
   • US FDA (www.fda.gov)
   • EMA (www.ema.europa.eu)
   • CDSCO (www.cdsco.gov.in)
   • WHO Prequalification Programme
   • Country-specific regulatory portals for targeted submission

5.2 Compilation of Applicable Guidelines

1. Document the applicable guidelines in Annexure-1: Regulatory Guidelines Summary Sheet.
2. Include:
   • Product-specific guidance (e.g., FDA PSG)
   • General GCP and BA/BE guidelines
   • Ethics and safety submission rules
   • Format and data submission (eCTD, XML, etc.)

5.3 Study Protocol Alignment

1. Ensure protocol design complies with relevant pharmacokinetic parameters, statistical methods, and population selection as per guideline recommendations.
2. Use Annexure-2: Protocol-Guideline Cross-Reference Table to confirm alignment.

5.4 Impact of Updates

1. Monitor for updated guidelines during study conduct and assess their impact using Annexure-3: Regulatory Update Impact Log.
2. Communicate changes and take action to amend documents or procedures as needed.

5.5 Filing and Communication

1. Store all reviewed guidelines and cross-reference documentation in the Trial Master File (TMF).
2. Share the summary with QA and Clinical Teams prior to study start.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• FDA: Food and Drug Administration
• EMA: European Medicines Agency
• CDSCO: Central Drugs Standard Control Organization
• GCP: Good Clinical Practice

7. Documents

1. Regulatory Guidelines Summary Sheet – Annexure-1
2. Protocol-Guideline Cross-Reference Table – Annexure-2
3. Regulatory Update Impact Log – Annexure-3

8. References

• ICH E6(R2) – Good Clinical Practice
• US FDA Product-Specific Guidance for BA/BE Studies
• EMA Guideline on the Investigation of Bioequivalence
• CDSCO Handbook for Clinical Trials

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Regulatory Guidelines Summary Sheet

Annexure-2: Protocol-Guideline Cross-Reference Table

Annexure-3: Regulatory Update Impact Log

Revision History:

Standard Operating Procedure for Compliance with ICH E6(R2) GCP Addendum in BA/BE Studies

1. Purpose

To define the process for implementing and ensuring compliance with the ICH E6(R2) Good Clinical Practice (GCP) Addendum requirements in Bioavailability and Bioequivalence (BA/BE) studies, with specific focus on quality management, sponsor oversight, and risk-based monitoring.

2. Scope

This SOP applies to all BA/BE studies sponsored or conducted by the organization, and includes regulatory submissions, CRO oversight, vendor qualification, clinical site operations, and data integrity practices as mandated under ICH E6(R2).

3. Responsibilities

• Quality Assurance (QA): Ensures organization-wide implementation of ICH E6(R2) elements through SOPs and training.
• Clinical Project Manager: Ensures study-specific application of quality risk management and oversight practices.
• Regulatory Affairs: Verifies compliance with E6(R2) requirements in submissions.
• IT/Data Management: Maintains data integrity, validation, and audit trail for electronic systems.

4. Accountability

The Head of Clinical Operations and the Head of QA are jointly accountable for ensuring compliance with ICH E6(R2) principles across all ongoing and future BA/BE trials.

5. Procedure

5.1 Sponsor Oversight

1. Ensure written oversight plans are in place for each contracted CRO and vendor using Annexure-1: CRO Oversight Checklist.
2. Conduct quarterly governance meetings and maintain minutes in the TMF.

5.2 Quality Management System (QMS)

1. Develop and maintain a Quality Management Plan (QMP) for each study.
2. Implement procedures to identify, document, and address quality issues, including deviations and CAPAs.

5.3 Risk-Based Monitoring (RBM)

1. Perform risk assessment prior to study initiation using Annexure-2: Risk Assessment Template.
2. Classify risks as critical, major, or minor, and develop mitigation plans accordingly.
3. Define centralized, remote, and on-site monitoring strategies.

5.4 Data Integrity and Documentation

1. Ensure source data meets ALCOA+ principles: Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, and Available.
2. Use validated electronic systems that generate audit trails and control user access.

5.5 Training and Compliance

1. All study personnel must be trained on ICH E6(R2) requirements using Annexure-3: Training Attendance Log.
2. Refresher training must be conducted annually or when SOPs are revised.

5.6 Continuous Improvement

1. Lessons learned and audit findings must be recorded and reviewed quarterly.
2. Update risk plans and QMPs as needed and document changes in Annexure-4: Quality Issue Log.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• RBM: Risk-Based Monitoring
• QMS: Quality Management System
• ALCOA+: Data Integrity Principles
• CRO: Contract Research Organization

7. Documents

1. CRO Oversight Checklist – Annexure-1
2. Risk Assessment Template – Annexure-2
3. Training Attendance Log – Annexure-3
4. Quality Issue Log – Annexure-4

8. References

• ICH E6(R2) – Guideline for Good Clinical Practice
• EMA Reflection Paper on Risk-Based Quality Management
• 21 CFR Part 11 – Electronic Records and Signatures

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: CRO Oversight Checklist

Annexure-2: Risk Assessment Template

Annexure-3: Training Attendance Log

Annexure-4: Quality Issue Log

Revision History:

Standard Operating Procedure for Trial Registration with EudraCT in BA/BE Studies

1. Purpose

To define the process for registering BA/BE clinical trials in the European Clinical Trials Database (EudraCT) in accordance with European Medicines Agency (EMA) requirements for transparency, regulatory compliance, and study oversight.

2. Scope

This SOP is applicable to all BA/BE studies that are required to be registered in the EudraCT system, either as part of regulatory submissions to EU member states or for clinical trial applications involving investigational medicinal products in Europe.

3. Responsibilities

• Regulatory Affairs: Responsible for initiating, completing, and submitting the EudraCT registration dossier.
• Clinical Project Manager: Provides protocol, site, and sponsor-related details required for registration.
• Quality Assurance: Verifies EudraCT documentation during audits and inspections.

4. Accountability

The Head of Regulatory Affairs is accountable for ensuring that no study involving EU submission proceeds without a valid EudraCT number and confirmation of registration completion.

5. Procedure

5.1 Pre-Registration Requirements

1. Ensure the final protocol and Investigator’s Brochure (IB) are approved and available in English.
2. Ensure the sponsor holds a valid EudraCT user account.
3. Obtain Ethics Committee (EC) contact and site details for inclusion in the form.

5.2 EudraCT Registration Steps

1. Log in to the European Commission EudraCT portal at https://eudract.ema.europa.eu/.
2. Select “Create Clinical Trial Application” and generate a new EudraCT number.
3. Fill in the required sections, including:
   • Trial identification
   • Sponsor and CRO details
   • Product and trial characteristics
   • Subject inclusion criteria
   • Safety and IMPD data
4. Upload supporting documents (protocol, IB, informed consent form).
5. Electronically sign and submit the application.

5.3 Confirmation and Documentation

1. Upon successful submission, download and archive the EudraCT summary report.
2. Record the generated EudraCT number in Annexure-1: Trial Registration Log.
3. Notify internal stakeholders and CRO partners regarding registration completion.

5.4 Amendments and Updates

1. For any protocol amendment or change in site/sponsor, update the trial entry in the EudraCT system within 15 days.
2. Maintain update records in Annexure-2: Registration Amendment Tracker.

5.5 Public Disclosure

1. Ensure clinical trial results are posted in the EU Clinical Trials Register within 12 months of study completion.
2. Responsibility lies with the sponsor to comply with posting timelines.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• EMA: European Medicines Agency
• IB: Investigator’s Brochure
• EC: Ethics Committee
• CRO: Contract Research Organization

7. Documents

1. Trial Registration Log – Annexure-1
2. Registration Amendment Tracker – Annexure-2

8. References

• EMA EudraCT User Manual
• Regulation (EU) No 536/2014 on Clinical Trials
• ICH E6(R2) – Good Clinical Practice

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Trial Registration Log

Annexure-2: Registration Amendment Tracker

Revision History:

Standard Operating Procedure for Project Risk Identification and Mitigation in BA/BE Studies

1. Purpose

To establish a structured approach for the identification, assessment, documentation, and mitigation of project risks in Bioavailability/Bioequivalence (BA/BE) studies, ensuring study continuity, data integrity, and regulatory compliance.

2. Scope

This SOP applies to all BA/BE studies conducted or sponsored by the organization, covering operational, regulatory, clinical, vendor, and timeline-related risks throughout the study lifecycle.

3. Responsibilities

• Clinical Project Manager (CPM): Leads the risk management process and maintains the Risk Register.
• Functional Department Heads: Identify functional risks and propose mitigation strategies.
• Quality Assurance (QA): Reviews the risk plan for regulatory alignment and audit preparedness.
• Regulatory Affairs: Assesses potential compliance risks.

4. Accountability

The Head of Clinical Operations is accountable for ensuring that risk management is integrated into the project management framework and reviewed periodically for adequacy and responsiveness.

5. Procedure

5.1 Risk Identification

1. Initiate risk identification during project kick-off.
2. Use Annexure-1: Risk Identification Template to document all foreseeable risks under the following categories:
   • Study Start-up (e.g., EC delays, site readiness)
   • Clinical Operations (e.g., volunteer dropout, protocol deviations)
   • Data Management (e.g., CRF entry backlogs)
   • Bioanalysis (e.g., sample loss, contamination)
   • Regulatory (e.g., import license delays, audit findings)

5.2 Risk Assessment

1. Rate each risk on:
   • Probability: Low (1), Medium (2), High (3)
   • Impact: Low (1), Medium (2), High (3)
2. Calculate Risk Score = Probability × Impact
3. Document in Annexure-2: Risk Assessment Matrix

5.3 Risk Mitigation and Contingency Planning

1. Develop mitigation plans for all risks with score ≥ 4.
2. Each mitigation plan should define:
   • Responsible person
   • Timeline
   • Resources required
3. Capture mitigation steps in Annexure-3: Risk Mitigation Plan

5.4 Risk Monitoring

1. Review the Risk Register bi-weekly during study meetings.
2. Update risk status (Open/Controlled/Closed) in Annexure-4: Risk Tracking Log

5.5 Lessons Learned

1. Post-study, conduct a risk review workshop.
2. Document key lessons in Annexure-5: Risk Closure and Learning Sheet

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• CPM: Clinical Project Manager
• EC: Ethics Committee
• CRF: Case Report Form

7. Documents

1. Risk Identification Template – Annexure-1
2. Risk Assessment Matrix – Annexure-2
3. Risk Mitigation Plan – Annexure-3
4. Risk Tracking Log – Annexure-4
5. Risk Closure and Learning Sheet – Annexure-5

8. References

• ICH Q9 – Quality Risk Management
• ICH E6(R2) – Good Clinical Practice
• CDSCO Guidance on Risk-based Study Oversight

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Risk Identification Template

Annexure-2: Risk Assessment Matrix

Annexure-3: Risk Mitigation Plan

Annexure-4: Risk Tracking Log

Annexure-5: Risk Closure and Learning Sheet

Revision History:

Standard Operating Procedure for Setting Up eTMF (Electronic Trial Master File) in BA/BE Studies

1. Purpose

To define the procedure for establishing and maintaining an Electronic Trial Master File (eTMF) system for BA/BE studies, ensuring real-time documentation, compliance with ICH-GCP guidelines, and audit readiness.

2. Scope

This SOP applies to all BA/BE studies where an eTMF is implemented to manage essential documents throughout the study lifecycle including planning, conduct, and closeout phases.

3. Responsibilities

• Clinical Document Manager: Leads the eTMF setup, configuration, and maintenance activities.
• Clinical Project Manager (CPM): Ensures timely upload and completeness of study-specific documents.
• Quality Assurance: Reviews eTMF structure and compliance during audits.
• IT Department: Provides technical support for access control, data backup, and software validation.

4. Accountability

The Head of Clinical Operations is accountable for ensuring the eTMF system is implemented, validated, and maintained in compliance with regulatory standards and internal policies.

5. Procedure

5.1 Selection and Validation of eTMF System

1. Select a validated eTMF platform with 21 CFR Part 11 compliance.
2. Complete IT validation documentation including user requirement specifications (URS), functional specification (FS), and validation summary report.

5.2 Folder Structure and Metadata Setup

1. Configure the folder structure as per the DIA Reference Model (Annexure-1: eTMF Folder Mapping).
2. Assign document metadata fields such as:
   • Study ID
   • Country/Site
   • Document Type
   • Version
   • Date

5.3 User Access and Permissions

1. Define user roles and access levels (e.g., Viewer, Editor, Approver).
2. Maintain user list in Annexure-2: eTMF Access Log.

5.4 Document Upload and QC

1. Upload essential documents into the appropriate folders following standardized naming conventions.
2. Each document must be reviewed and quality-checked before final approval.
3. Track version history and archival status for every file.

5.5 Milestone Tracking and Completeness Check

1. Configure milestone-based document tracking (e.g., Site Initiation, First Subject First Visit, Database Lock).
2. Use Annexure-3: eTMF Completeness Checklist to monitor document availability for each milestone.

5.6 Archival and Closeout

1. Post-study, lock the eTMF and generate audit trail report.
2. Export eTMF to secure archival location with backup maintained for 15 years (or as per regional regulations).

6. Abbreviations

• eTMF: Electronic Trial Master File
• CPM: Clinical Project Manager
• GCP: Good Clinical Practice
• DIA: Drug Information Association
• URS: User Requirement Specification

7. Documents

1. eTMF Folder Mapping – Annexure-1
2. eTMF Access Log – Annexure-2
3. eTMF Completeness Checklist – Annexure-3

8. References

• ICH E6(R2) – Good Clinical Practice
• 21 CFR Part 11 – Electronic Records and Signatures
• DIA TMF Reference Model

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: eTMF Folder Mapping

Annexure-2: eTMF Access Log

Annexure-3: eTMF Completeness Checklist

Revision History:

Standard Operating Procedure for Study Timelines and Milestone Management in BA/BE Studies

1. Purpose

To define the process for planning, monitoring, and managing study timelines and key milestones in Bioavailability/Bioequivalence (BA/BE) studies to ensure adherence to project deadlines, resource coordination, and regulatory deliverables.

2. Scope

This SOP applies to all BA/BE studies conducted or sponsored by the organization and involves all internal teams and external vendors responsible for study execution, data generation, and regulatory submission.

3. Responsibilities

• Clinical Project Manager (CPM): Prepares and maintains the study timeline tracker and ensures milestone adherence.
• Functional Department Leads: Provide timeline estimates and update progress for their respective deliverables.
• Quality Assurance: Reviews milestone completion status during internal audits and inspections.

4. Accountability

The Head of Clinical Operations is accountable for ensuring the implementation and compliance with project timelines and escalation of deviations to senior management.

5. Procedure

5.1 Timeline Planning

1. At project initiation, define the detailed timeline using Annexure-1: Study Timeline Tracker Template.
2. Include all critical milestones such as:
   • Protocol finalization
   • Ethics committee approval
   • Site readiness
   • First volunteer screened
   • Last volunteer dosed
   • Sample analysis completion
   • Statistical report delivery
   • Final CSR and regulatory submission

5.2 Tracking and Updates

1. Update the tracker weekly or as per the project governance model.
2. Review progress during weekly study team meetings.
3. Record deviations in Annexure-2: Timeline Deviation Log with justification and impact analysis.

5.3 Escalation and Corrective Actions

1. If a milestone is delayed by more than 5 working days:
   • Initiate an internal escalation to the study oversight committee.
   • Identify root cause and corrective actions.

5.4 Completion and Closure

1. Upon completion of the final study milestone (CSR sign-off or regulatory submission), conduct a milestone reconciliation review.
2. Document closure in Annexure-3: Milestone Closure Summary Sheet.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• CPM: Clinical Project Manager
• CSR: Clinical Study Report
• SOP: Standard Operating Procedure

7. Documents

1. Study Timeline Tracker Template – Annexure-1
2. Timeline Deviation Log – Annexure-2
3. Milestone Closure Summary Sheet – Annexure-3

8. References

• ICH E6(R2) – Good Clinical Practice
• Internal Clinical Project Management Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Study Timeline Tracker Template

Annexure-2: Timeline Deviation Log

Annexure-3: Milestone Closure Summary Sheet

Revision History:

Standard Operating Procedure for Establishing Quality Agreements with CROs in BA/BE Studies

1. Purpose

To define the procedure for establishing formal Quality Agreements with Contract Research Organizations (CROs) involved in Bioavailability/Bioequivalence (BA/BE) studies to ensure mutual understanding of responsibilities, quality standards, and regulatory compliance.

2. Scope

This SOP applies to all CROs contracted for clinical operations, bioanalytical services, data management, pharmacovigilance, and other critical services in BA/BE studies sponsored or managed by the organization.

3. Responsibilities

• Quality Assurance (QA): Leads the drafting, review, and approval process of the Quality Agreement.
• Clinical Project Manager: Coordinates functional input and ensures agreement execution prior to study start.
• Legal and Contracts Department: Reviews legal language and ensures alignment with Master Service Agreement (MSA).
• CRO Representative: Reviews and signs agreement acknowledging their obligations.

4. Accountability

The Head of Quality is accountable for ensuring that no work is initiated by the CRO unless a fully executed Quality Agreement is in place, filed, and accessible to relevant stakeholders.

5. Procedure

5.1 Initiating the Quality Agreement

1. Trigger for Quality Agreement initiation includes:
   • Selection of a CRO for a BA/BE study
   • Amendment or renewal of existing service contracts
2. Use Annexure-1: Quality Agreement Template as the starting document.

5.2 Content of the Agreement

1. The agreement shall include but not be limited to:
   • Scope of services
   • Compliance with ICH E6(R2), Schedule Y, GLP, and GCP
   • Roles and responsibilities of both sponsor and CRO
   • Data ownership and integrity
   • Deviation and CAPA management
   • Audit and inspection readiness
   • Document retention and confidentiality

5.3 Review and Finalization

1. Circulate the draft internally to relevant departments for comments using Annexure-2: Quality Agreement Review Log.
2. Share the updated draft with CRO for mutual review and alignment.
3. Legal department validates language prior to execution.

5.4 Execution and Archival

1. Both parties sign the final document; each retains a signed copy.
2. File executed agreement in Trial Master File (TMF) and QA Agreement Repository.

5.5 Monitoring and Amendment

1. Review agreement validity annually or at the time of major protocol or service change.
2. Any change in scope must be captured through an amended agreement with updated signatures.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• CRO: Contract Research Organization
• QA: Quality Assurance
• TMF: Trial Master File

7. Documents

1. Quality Agreement Template – Annexure-1
2. Quality Agreement Review Log – Annexure-2

8. References

• ICH E6(R2) – Good Clinical Practice
• Schedule Y – Drugs and Cosmetics Rules
• EMA Reflection Paper on CRO Oversight

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Quality Agreement Template

Annexure-2: Quality Agreement Review Log

Revision History:

Standard Operating Procedure for Third-Party Vendor Qualification (Labs, Courier) in BA/BE Studies

1. Purpose

To define the standardized process for evaluating, qualifying, and approving third-party vendors including bioanalytical labs, logistics providers, and courier services involved in Bioavailability/Bioequivalence (BA/BE) studies.

2. Scope

This SOP applies to all external vendors providing critical services in BA/BE studies sponsored or managed by the organization. This includes bioanalytical laboratories, central labs, sample transport couriers, and document logistics partners.

3. Responsibilities

• Quality Assurance (QA): Leads vendor audit and qualification process.
• Clinical Project Manager: Initiates vendor selection and coordinates documentation flow.
• Regulatory Affairs: Confirms licensing and accreditation status of vendor.
• Procurement: Ensures agreements, pricing, and contracts are in place post-qualification.

4. Accountability

The Head of Quality is accountable for ensuring that no unqualified or unapproved vendor is engaged in any critical trial-related activity that can impact subject safety or data integrity.

5. Procedure

5.1 Vendor Identification and Initiation

1. Identify potential vendors based on study requirements and geographical feasibility.
2. Send Annexure-1: Vendor Prequalification Questionnaire for initial screening.

5.2 Documentation Review

1. Collect the following from the vendor:
   • Company profile and GMP/GLP certification
   • List of equipment and validation records
   • Sample transportation SOPs and temperature monitoring procedures
   • Quality policy and past audit reports (if applicable)

5.3 Site Audit and Technical Evaluation

1. Conduct an on-site or remote audit using Annexure-2: Vendor Audit Checklist.
2. Evaluate parameters including:
   • Sample handling capacity and storage conditions
   • Turnaround time and contingency plans
   • Personnel training and documentation practices

5.4 Approval and Onboarding

1. Document findings in Annexure-3: Vendor Qualification Summary.
2. Obtain final approval from QA Head using Annexure-4: Vendor Approval Form.
3. Enter qualified vendor into Annexure-5: Approved Vendor Master List.

5.5 Periodic Requalification

1. Vendors shall be re-evaluated every 2 years or after significant non-compliance events.
2. Conduct spot audits if required and update qualification status accordingly.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• GLP: Good Laboratory Practice
• QA: Quality Assurance
• SOP: Standard Operating Procedure

7. Documents

1. Vendor Prequalification Questionnaire – Annexure-1
2. Vendor Audit Checklist – Annexure-2
3. Vendor Qualification Summary – Annexure-3
4. Vendor Approval Form – Annexure-4
5. Approved Vendor Master List – Annexure-5

8. References

• ICH E6(R2) – Good Clinical Practice
• OECD Principles of GLP
• WHO Guidelines for the Preparation of BA/BE Protocols

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Vendor Prequalification Questionnaire

Annexure-2: Vendor Audit Checklist

Annexure-3: Vendor Qualification Summary

Annexure-4: Vendor Approval Form

Annexure-5: Approved Vendor Master List

Revision History:

Standard Operating Procedure for Clinical Trial Budget Preparation and Approvals in BA/BE Studies

1. Purpose

To define the procedure for preparing and obtaining approval for the clinical trial budget associated with Bioavailability/Bioequivalence (BA/BE) studies, including cost estimation, review, negotiation, finalization, and documentation.

2. Scope

This SOP applies to all BA/BE studies conducted or sponsored by the organization and covers budgeting activities for internal resources, site payments, CRO services, laboratory testing, volunteer reimbursements, and contingency funds.

3. Responsibilities

• Clinical Project Manager: Initiates and prepares the draft study budget in consultation with relevant departments.
• Finance Department: Verifies financial projections, vendor rates, and payment timelines.
• Regulatory Affairs: Confirms budget covers all submission and approval fees.
• Site Management Team: Coordinates site budget negotiation and obtains approval from the Principal Investigator.

4. Accountability

The Head of Clinical Operations is accountable for ensuring that each BA/BE study has a finalized and approved budget in place before the initiation of any contractual commitments or clinical activities.

5. Procedure

5.1 Budget Planning Initiation

1. Initiate budget planning during protocol development or feasibility stage.
2. Use Annexure-1: Clinical Trial Budget Template to list all anticipated line items.

5.2 Cost Components to be Included

1. Include the following cost elements:
   • Site fees (screening, randomization, completion)
   • Volunteer compensation and meals
   • Clinical supplies and lab kits
   • Bioanalytical sample analysis
   • Regulatory and EC submission fees
   • Insurance premiums
   • CRO/vendor fees
   • Monitoring travel and overheads
   • Archival and TMF maintenance
   • Contingency (5–10%)

5.3 Internal Review and Revisions

1. Circulate draft budget internally for review using Annexure-2: Budget Review Log.
2. Revise based on feedback from functional teams.

5.4 Site and Vendor Budget Negotiation

1. Share budget breakdown with site and CRO for review.
2. Negotiate line items where required and document changes in Annexure-3: Negotiation Summary Sheet.

5.5 Final Approval and Execution

1. Compile finalized budget with signatures using Annexure-4: Final Budget Approval Form.
2. Store all budget documents in the Trial Master File (TMF).
3. Use approved budget as baseline for future cost tracking and reconciliation.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• CRO: Contract Research Organization
• EC: Ethics Committee
• TMF: Trial Master File

7. Documents

1. Clinical Trial Budget Template – Annexure-1
2. Budget Review Log – Annexure-2
3. Negotiation Summary Sheet – Annexure-3
4. Final Budget Approval Form – Annexure-4

8. References

• ICH E6(R2) – Good Clinical Practice
• Schedule Y – Drugs and Cosmetics Rules
• Internal Clinical Study Finance SOP

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Clinical Trial Budget Template

Annexure-2: Budget Review Log

Annexure-3: Negotiation Summary Sheet

Annexure-4: Final Budget Approval Form

Revision History:

Standard Operating Procedure for Review of Subject Recruitment Feasibility in BA/BE Studies

1. Purpose

To define the procedure for reviewing and documenting the feasibility of recruiting healthy volunteers or study subjects for Bioavailability/Bioequivalence (BA/BE) studies in order to ensure timely completion of enrollment and avoid protocol deviations.

2. Scope

This SOP applies to all BA/BE studies planned by the organization or outsourced to CROs, and includes pre-study feasibility assessment, documentation, and monitoring of recruitment plans for healthy adult volunteers or special populations, if applicable.

3. Responsibilities

• Clinical Project Manager: Coordinates feasibility assessments and compiles the feasibility report.
• Site Coordinator/Investigator: Provides actual recruitment capability data based on past records.
• Regulatory Affairs: Assesses if any restrictions apply (e.g., ethics caps on enrollment).
• Medical Affairs: Reviews inclusion/exclusion criteria for practical applicability.

4. Accountability

The Head of Clinical Operations is accountable for ensuring that a realistic and documented recruitment plan is in place before first subject screening is authorized.

5. Procedure

5.1 Initiation of Feasibility Assessment

1. Initiate feasibility assessment during the protocol finalization phase or at least 4 weeks prior to planned study start.
2. Use Annexure-1: Subject Recruitment Feasibility Questionnaire to collect site-specific information.

5.2 Data Collection Parameters

1. Collect the following data from study sites:
   • Historical enrollment data for similar BA/BE studies
   • Average screening-to-enrollment ratio
   • Volunteer pool database size
   • Number of similar studies planned at the site during the same period
   • Availability of healthy volunteers meeting protocol criteria

5.3 Feasibility Analysis and Risk Assessment

1. Review the protocol to identify restrictive criteria (e.g., BMI, lab values, washout requirements).
2. Conduct SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis for each site.
3. Document analysis using Annexure-2: Site Recruitment Feasibility Summary.

5.4 Recruitment Strategy and Contingency Planning

1. Define the following in the recruitment plan:
   • Number of volunteers needed vs. site capacity
   • Backup sites (if applicable)
   • Contingency for screen failures and dropouts
   • Communication materials (approved recruitment flyers, SMS templates)
2. Capture in Annexure-3: Study Recruitment Plan Log.

5.5 Approval and Filing

1. Ensure all annexures are completed and approved by the Clinical Project Manager.
2. File in the Trial Master File (TMF) and make available for ethics and regulatory review, if requested.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• TMF: Trial Master File
• SWOT: Strengths, Weaknesses, Opportunities, Threats

7. Documents

1. Subject Recruitment Feasibility Questionnaire – Annexure-1
2. Site Recruitment Feasibility Summary – Annexure-2
3. Study Recruitment Plan Log – Annexure-3

8. References

• ICH E6(R2) – Good Clinical Practice
• Schedule Y – Drugs and Cosmetics Rules
• EMA Clinical Trial Recruitment Guidance

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Subject Recruitment Feasibility Questionnaire

Annexure-2: Site Recruitment Feasibility Summary

Annexure-3: Study Recruitment Plan Log

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