3. Responsibilities

• Bioanalytical Analyst: Prepares and labels QC samples as per protocol and maintains preparation records.
• Reviewer (Team Lead/QA): Verifies the concentration, labeling, and documentation of QC samples.
• Lab Supervisor: Approves QC sample usage for analytical batches.

4. Accountability

The Head of Bioanalytical Department is accountable for ensuring correct preparation, traceability, and stability compliance of all QC samples used in regulated studies.

5. Procedure

5.1 Selection of QC Levels

1. Determine QC levels based on the calibration range established for the analyte.
2. Typical levels include:
   • LLOQ QC
   • Low QC (≈3× LLOQ)
   • Medium QC (≈30–50% of range)
   • High QC (≈80–85% of range)
3. Include Dilution QC (DQC) and Reinjection QC (RIQC) as required by study protocol.

5.2 Preparation of QC Working Solution

1. Prepare working solution by diluting certified reference stock solution using a suitable solvent or buffer.
2. Calculate concentrations for each QC level and document in Annexure-1: QC Working Solution Preparation Log.

5.3 Spiking of QC Samples

1. Aliquot blank matrix (e.g., human plasma) into pre-labeled tubes.
2. Add calculated volume of QC working solution to obtain desired final concentration.
3. Mix samples thoroughly and ensure homogeneity.
4. Prepare a minimum of 6 replicates per level for validation and 2 replicates per level for routine batches.
5. Record preparation details in Annexure-2: QC Spiking Sheet.

5.4 Labeling of QC Samples

1. Each tube must be labeled with:
   • QC Level
   • Analyte Name
   • Matrix Type
   • Date of Preparation
   • Expiry Date
2. Use barcodes if required by LIMS or SOP.

5.5 Storage and Stability

1. Store QC samples at defined temperatures (-20°C or -70°C) as per analyte stability data.
2. Stability must be evaluated during method validation (short-term, freeze-thaw, long-term, and post-preparative).
3. Maintain Annexure-3: QC Storage and Stability Log.

5.6 Use in Analytical Batches

1. Include at least 2 replicates of each QC level in every analytical run.
2. Acceptance Criteria:
   • ≥67% of all QC results must be within ±15% of nominal (±20% for LLOQ QC).
   • At least 50% of QC results at each level must pass.
3. In case of batch rejection, initiate investigation as per deviation handling SOP.

5.7 Documentation and Archival

1. All preparation records must be signed, dated, and independently verified.
2. Scan and upload documents into the electronic document management system (EDMS) where applicable.

6. Abbreviations

• BA/BE: Bioavailability/Bioequivalence
• QC: Quality Control
• LLOQ: Lower Limit of Quantification
• DQC: Dilution Quality Control
• RIQC: Reinjection Quality Control
• LIMS: Laboratory Information Management System

7. Documents

1. QC Working Solution Preparation Log – Annexure-1
2. QC Spiking Sheet – Annexure-2
3. QC Storage and Stability Log – Annexure-3

8. References

• ICH M10 – Bioanalytical Method Validation Guidelines
• US FDA Guidance for Bioanalytical Method Validation
• EMA Guideline on Bioanalytical Method Validation

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: QC Working Solution Preparation Log

Date	Analyte	Concentration	Diluent	Prepared By
15/04/2025	ABC-123	100 µg/mL	Methanol	Rajesh Kumar

Annexure-2: QC Spiking Sheet

QC Level	Target Conc. (ng/mL)	Matrix Volume	Spike Volume	Total Volume	Prepared By
LQC	50	450 µL	50 µL	500 µL	Sunita Reddy

Annexure-3: QC Storage and Stability Log

QC ID	Level	Prep Date	Storage Temp	Stability Data	Status
QC-ABC-01	LQC	15/04/2025	-20°C	Stable	Valid

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial release	New SOP	QA Head
17/04/2025	2.0	Expanded procedure and annexures for ICH M10 alignment	Compliance Enhancement	QA Head