Standard Operating Procedure for Handling Deviations in PK Sampling Time in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/125/2025 |
| Supersedes | SOP/BA-BE/125/2022 |
| Page No. | Page 1 of 10 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define the procedure for identifying, managing, and documenting deviations from the planned pharmacokinetic (PK) blood sampling schedule in bioavailability/bioequivalence (BA/BE) studies to ensure accurate bioanalytical interpretation and regulatory compliance.
2. Scope
This SOP applies to all clinical and bioanalytical personnel involved in the collection, documentation, and evaluation of PK samples in BA/BE studies conducted at the clinical research facility.
3. Responsibilities
- Phlebotomist/Nurse: Accurately collects samples at specified time points and reports any delay.
- Clinical Research Coordinator: Logs the actual sampling time and assesses deviation magnitude.
- Principal Investigator: Reviews and signs off on deviation documentation.
- QA Personnel: Audits sampling logs for compliance and trending.
4. Accountability
The Clinical Operations Manager is accountable for ensuring that all deviations in PK sampling time are identified, recorded, assessed, and communicated appropriately to maintain study data integrity.
5. Procedure
5.1 Definition of PK Sampling Deviation
- Deviation is defined as any sampling time that falls outside the permitted ± window as specified in the protocol (commonly ±2 min to ±5 min depending on the time point).
- Minor deviations (within protocol-specified range) are to be recorded but do not require CAPA.
- Major deviations (outside window or missed samples) must be documented and evaluated for impact.
5.2 Documentation of Actual Sampling Time
- Record actual time of blood collection in 24-hour format on:
- PK Sampling Log
- CRF
- Source Document
- Use Annexure-1: PK Sampling Deviation Log to document any deviations.
5.3 Categorization and Evaluation
- Deviations shall be categorized as:
- Early Sample: Collected before scheduled time
- Late Sample: Collected after scheduled time
- Missed Sample: Not collected at all
- Evaluate the impact based on:
- Time point (e.g., Cmax, Tmax critical points)
- Deviation duration
- Frequency of occurrence
- Involve Bioanalytical Principal Scientist in decision-making if required.
5.4 CAPA and Communication
- Prepare a CAPA using Annexure-2: PK Sampling Deviation CAPA Form for major deviations.
- Communicate the deviation in the site deviation report and include in study summary.
- Notify the sponsor or regulatory body if deviation is frequent or critical (as per agreement).
5.5 Trend Analysis and Preventive Actions
- QA shall review sampling deviations monthly.
- Implement retraining, checklist improvements, or automated alarms to reduce reoccurrence.
- Document preventive actions in Annexure-3: Deviation Trending Log.
6. Abbreviations
- PK: Pharmacokinetic
- BA: Bioavailability
- BE: Bioequivalence
- CRF: Case Report Form
- CAPA: Corrective and Preventive Action
- QA: Quality Assurance
7. Documents
- PK Sampling Deviation Log – Annexure-1
- PK Sampling Deviation CAPA Form – Annexure-2
- Deviation Trending Log – Annexure-3
8. References
- ICH E6(R2) – Good Clinical Practice
- US FDA Bioanalytical Method Validation Guidance
- Protocol-specific time window definitions
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: PK Sampling Deviation Log
| Subject ID | Scheduled Time | Actual Time | Deviation (min) | Type | Remarks |
|---|---|---|---|---|---|
| V021 | 10:00 | 10:07 | +7 | Late | Volunteer delay |
Annexure-2: PK Sampling Deviation CAPA Form
| Deviation Description | Root Cause | Corrective Action | Preventive Action | Closed By |
|---|---|---|---|---|
| Missed 4-hr sample | Shift handover error | Reminder checklist added | Shift logbook updated | QA Manager |
Annexure-3: Deviation Trending Log
| Month | Total PK Samples | Deviations | % Deviation | Comments |
|---|---|---|---|---|
| March 2025 | 960 | 14 | 1.46% | Within limit |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 10/01/2022 | 1.0 | Initial SOP Release | Regulatory Requirement | QA Head |
| 17/04/2025 | 2.0 | Added trending and early/late deviation classification | Audit Observation | QA Head |