revison

Originator Approval		Date:
R&D Approval		Date:
QC Approval		Date:
QA Approval		Date:
Regulatory Affairs Approval		Date

TABLE OF CONTENTS

21 Study Overview

2 Materials/Methods 3

3 Data Recording and Analysis 5

4 Interpretation of Results 5

5 Reagent Requirements 6

6 Validity Criteria 6

7 Repeat Testing Criteria 6

8 Failure Investigation 7

9 Appendix B: Stability Study Deviation Log 8

10 APPENDIX B: SUMMARY OF MATERIALS AND METHODS 9

Magnetic Particles for Target Capture Reagent 9

1 Study Overview

1.1 Objectives

1.2 The objective of this protocol is to provide stability data to support the dating of the Seradyn Magnetic Particles and dT14 Magnetic Particles used in the manufacture of the Target Capture Reagent in the TMA HIV-1/HCV Assay master kit. These Magnetic Particles are stored for extended periods after manufacture but prior to final reagent formulation. In addition, data will be generated to show the Raw Material/Subassembly stay within specification when stored under the recommended conditions during proposed storage times as defined in the QS or QCS documents.

1.3 Definitions

1.3.1 Component: Global term to identify any labeled reagent, subassembly or raw material.

1.3.2 Raw Material: Component manufactured by outside Vendor that is used in manufacture of a second component.

1.3.3 Real Time Stability Study: Subassemblies are incubated at their proposed long term storage temperature for a period of time exceeding the proposed shelf life of the product by at least 20%.

1.3.4 Subassembly: Intermediates in the manufacturing process of the labeled reagents.

1.4 Referenced Documents

1.4.1 See Appendix A for Summary of Testing and Methods

1.4.2 SOP from Quadrants Scientific, Inc. V-077: Bioburden Analysis of Cougar Samples for Aerobic Bacteria, Yeast, and Mold

1.5 Equipment: All of the equipment used to execute the stability studies for testing will be qualified, calibrated, validated and maintained according to Cougar quality requirements.

1.6 Roles and Responsibilities

1.6.1 It will be the responsibility of R&D, QC, QA, and Regulatory Affairs to review and approve the study protocols and study report.

1.6.2 It will be the responsibility of Product Support, QC and Alexon-Trend, Inc. to set up and perform the testing required to complete the study according to approved Cougar SOPs, unless otherwise specified in this protocol. The testing includes quantitative assay performance and analytical testing.

1.6.3 It will be the responsibility of Product Support and QC to perform and document any required investigations.

1.6.4 It will be the responsibility of QC to write the final stability study reports.

2 Materials/Methods

2.1 Materials

2.1.1 This study will be performed on a minimum of three lots of Seradyn Magnetic Particles and dT14 Magnetic Particles made with final manufacturing processes and used in the production of the TMA HIV-1/HCV Assay reagents. Magnetic Particles used will be QC tested and approved for inventory prior to undergoing stability testing.

2.1.2 The Magnetic Particles will be stored in containers made from the same material as from the manufacturer only in lesser volume. The volume used for stability storage will be less than but proportional to that stated in the manufacturing documents.

2.1.2.1 Magnetic Particles will be stored in 2 containers. Aliquots will be removed at each time point from a single specified container for testing. The additional container will be used for investigation purposes or supplemental testing.

2.1.3 All subassemblies will be stored in final storage containers as stated in manufacturing documents. Unless otherwise specified, the volumes used for stability storage will be as stated in the manufacturing documents. Biological Inventory Cards will be kept for subassemblies for IC, HIV, and HCV.

2.2 Temperatures

The Magnetic Particles will be stored at their specific storage conditions as described in the manufacturing specifications. Storage temperatures for the Magnetic Particles will be 2-8oC.

2.3 Time Points

2.3.1 Magnetic Particles

1.6.4.1 2.3.1.1 Time Points for analytical testing: Real time stability time points to be tested are baseline (0) and testing intervals of 6, 12, 18, 24, and 30 months. Time point range is + 14 days to accommodate analytical testing. Additional time points may be tested based on results from any given month.

1.6.4.2 2.3.1.2 Time points for Bioburden will be Baseline and at Month 30.

2.3.2 dT14 Magnetic Particles

2.3.2.1 Time points for analytical testing: Real time stability time points to be tested are baseline (0) and testing intervals of 3, 6, 9, 12, 15, 18, 24, and 30 months. Time point range is + 14 days to accommodate analytical testing. Additional time points may be tested based on results from any given month.

2.3.3 Summary of time points for analytical testing

Description	Month
	0	3	6	9	12	15	18	24	30
Magnetic Particles	X		X		X		X	X	X
DT14 Magnetic Particles	X	X	X	X	X	X	X	X	X

2.4 Testing Procedures

2.4.1 Magnetic Particles

2.4.1.1 The vendor will perform the COOH Content per their protocol.

2.4.1.2 Concentration testing will be performed.

2.4.1.3 A small scale coupling will be performed according to DTP XXXX. Binding Capacity will then be performed on this small scale coupling product.

2.4.1.4 Bioburden will be performed.

2.4.1.5 Microscopic examination for agglomeration or aggregation will be performed.

2.4.2 DT14 Magnetic Particles: Analytical testing includes Binding Capacity Assay and Concentration. For the Binding Capacity Assay, ten replicates will be performed on the following dilutions made with the dT14 Magnetic Particles at each time point: 0, 10, 20, 40, and 60 (g.

2.5 Evaluations

2.5.1 Baseline Determination

2.5.1.1 QC lot release data will be used for the baseline determination on the Magnetic Particles. Scheduled time points for stability testing will be determined from the Manufacturing date.

2.5.2 Subassembly/Component Dating: The expiry dating of the subassemblies/components will be 80% of the last acceptable time point. In the event failure is not observed expiry dating will be based on the completion of the stability study, minus 20%.

2.6 Deviations

All deviations from the protocol described must be docomented on a deviation report (reference Appendix A).

3 Data Recording and Analysis

3.1 Analytical testing results for the Magnetic Particles will be filed according to QC procedures. Records will include the Protocol number, time point, test description, lot number, lot number of all reagents included in testing, equipment ID, operator’s signature and date. A stability database will be established.

3.1.1 All valid data will be analyzed, tracked graphically as well as tabulated.

4 Interpretation of Results

1.7 Failure is defined as the point in time when specifications listed in Appendix B are not met.

5 Reagent Requirements

5.1 Reagent Quantity Requirements

1.8 The total includes the minimum required plus additional for retest, investigational use or for appropriate storage volume per container.

1.9 Description	1.10 P/N	1.11 Proposed Expiry Date	1.12 Storage Temp	1.13 Vol/Time Point	1.14 Time Points	1.15 Total Required	1.16 Final Volume
1.17 Magnetic Particles	1.18 PCH0206	1.19 2 yr	1.20 2-8 0C	1.21 1 mL	1.22 6	1.23 6 mL	1.24 Variable
1.25 dT14 Magnetic Particles	1.26 PSA0221	1.27 2 yr	1.28 2-8 0C	1.29 1 mL	1.30 9	1.31 9 mL	1.32 Variable

5.2 Reagent Storage Volume/Container Requirements

1.33 The following table indicates the storage container material used and fill volume for the manufactured component and for the sample used in the stability study.

1.34 Description	1.35 P/N	1.36 Mfg. Storage Container	1.37 Mfg. Storage Volume	1.38 Container Material	1.39 Stability Storage Container	1.40 Stability Storage Volume	1.41 Container Material
1.42 Magnetic Particles	1.43 PCH0206	1.44 Screw-capped Container	1.45 100 mL	1.46	1.47 Screw-capped Container	1.48 Variable	1.49
1.50 dT14 Magnetic Particles	1.51 PSA0221	1.52 HDPE	1.53 1.5 L/2 L Bottle	1.54 HDPE	1.55 HDPE	1.56 Variable	1.57 HDPE

6 Validity Criteria

6.1 Validity criteria will be followed as stated in the individual SOPs specified in Appendix B.

7 Repeat Testing Criteria

7.1 Repeat Testing Criteria – Assays will be reviewed using the established validity/acceptance criteria. Repeat testing will be performed according to guidelines established in the OOS procedures (10-01-20, 10-01-07-051,10-01-07-208) unless otherwise specified in the stability protocol. OOS forms applicable to stability studies will be used. Proceed to section 8 for failure investigation, if necessary.

8 Failure Investigation

8.1 Investigations: If a stability failure is confirmed, an investigation will be initiated. The following guidelines may be used:

8.1.1 Review QC release data.

8.1.2 If available, perform retest with control sample.

8.2 Investigation Reports and Out of specification Reports: All investigation reports and OOS reports will be written and made available for review by team members (R & D, RA, QC, QA). Investigation and OOS reports will be submitted with the final stability summary report.

9 Appendix B: Stability Study Deviation Log

Protocol Section/Page:______________________

Deviation Number*:________

Deviation Description:____________________________________________________________

_______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Justification/Impact Assessment:___________________________________________________ _____________________________________________________________________________

______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Completed by:_____________________________ Date:_______________________________

Approved by:______________________________ Date:_______________________________

*Filled in by Study Coordinator

10 APPENDIX B: SUMMARY OF MATERIALS AND METHODS

Magnetic Particles for Target Capture Reagent

Description	Storage Temp	P/N	Analytical Test	Specifications
Magnetic particles	2-8oC	PCH0206	COOH Content (performed by Vendor)	Acceptable Limits: 0.4 to 0.7 meq/g
			10-01-07-118 Concentration	Acceptable Limits: 40 to 60 mg/mL
			10-01-07-081 Binding Capacity Assay	Acceptable Limits: > 4.4 BCU/(g
			10-01-07-187 Bioburden	Acceptable Limits: < 10
			Microscopic Examination	Particle must be free flowing or showing agglomeration (flocculant and easily dispersed): Particles may not be aggregated (not capable of being dispersed). Particle Size Acceptable Limits: 0.68 to 1.00 (m
dT14-Magnetic Particles	2-8oC	PSA0221	10-01-07-081 Binding Capacity 10-01-07-118 Concentration	Binding Capacity:>4.4 BCU/(g Concentration: 6-14 mg/mL