Quality Documentation Documentation Overview The Quality Manual Types of Quality Documentation Quality Documentation Four Attributes of GMP Documentation Types of Documents SOP: Standard Operating Procedure Examples of SOP Categories Typical SOPs Components of an SOP Control of SOPs Control of SOPs Raw Material Specifications Raw Materials Raw Materials Example Product Specifications Master/Batch Production and Control Records Master/Batch Production Records EBR Laboratory Records Equipment Cleaning and Use Logs Equipment Log Example Distribution Records Complaint Files Document Format Why All The Documentation Everything you always wanted to know about good documentation but were afraid someone might tell you Everything you always wanted to know about good documentation but were afraid someone might tell you Good Documentation Practices Everything you always wanted to know about good documentation but were afraid someone might tell you ENTRIES ELECTRONIC RECORDS ELECTRONIC RECORDS (con’t) ELECTRONIC RECORDS (con’t) COUGAR Pharmaceuticals Proprietary Information Project Name: Magnetic Particle Real Time Stability Protocol Project Number:1002 Protocol Number: QCSASS-03 Date: 7/16/01 Page: 4 of 9 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 Overview1.1 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 ...

1. Quality Documentation
Documentation Overview
The Quality Manual
Types of Quality Documentation
Quality Documentation
Four Attributes of GMP Documentation

2. Types of Documents
SOP: Standard Operating Procedure
Examples of SOP Categories
Typical SOPs
Components of an SOP
Control of SOPs
Control of SOPs
Raw Material Specifications
Raw Materials

3. Raw Materials Example
Product Specifications
Master/Batch Production and
Control Records
Master/Batch Production Records
EBR

4. Laboratory Records
Equipment Cleaning and Use Logs
Equipment Log Example
Distribution Records
Complaint Files
Document Format
Why All The Documentation
Everything you always wanted to know about good
documentation but were afraid someone might tell you

5. Everything you always wanted to know about good
documentation but were afraid someone might tell you
Good Documentation Practices
Everything you always wanted to know about good
documentation but were afraid someone might tell you
ENTRIES
ELECTRONIC RECORDS
ELECTRONIC RECORDS (con’t)
ELECTRONIC RECORDS (con’t)

6. COUGAR Pharmaceuticals
Proprietary Information
Project Name: Magnetic Particle Real Time Stability Protocol
Project Number:1002
Protocol Number: QCSASS-03
Date: 7/16/01 Page: 4 of 9
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

7. 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 Overview1.1 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

8. 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

9. 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

10. 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

11. X
X
X
X
X
X
X
X2.4 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

12. 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

13. 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

14. 1.32 Variable5.2 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

15. 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 HDPE6 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.

16. 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:__________________________________________
_________
_____________________________________________________
________________________
_____________________________________________________
_____________________________________________________

17. _____________________________________________________
_____________________________________________________
_____________________________________________________
_____________________________________________________
_____________________________________________________
_____________________________________________________
______________________________________
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
DescriptionStorage TempP/NAnalytical TestSpecifications
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

18. 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
_972748512.doc
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Homework 6: SOP revision
Change in SOPs is part of manufacturer’s attempts for
continuous improvement of a process or product. PAGE gels
can be cast by an analyst (video 1 – mostly FYI), but a faster,
more reproducible way is to buy pre-cast gels (used in video 2).
In this exercise, you, the QC analyst, are preparing a draft of a
proposed revision of your current SOP for detecting a protein
product, to an improved one that uses pre-cast gels.

19. Pick a name for your biotech company. For your revised cGMP
compliant SOP, combine the instructions from video 2 for SDS-
PAGE, with the instructions for Western blotting given below in
text. Video 3 is provided to help you see and understand the
Western steps. You will have to stop at step 9 (or 8) of video 2
and continue on to the appropriate Western Blotting step in the
provided Western Blot protocol. Note that the Western Blot
protocol below is missing parts of what will be considered a
cGMP-compliant SOP format – you will have to add those
missing parts. You can follow the content and format of an
SOP in the “Label control SOP” and in the “SOP Stability
Cougar”. Also look for the parts of a cGMP-compliant SOP
from lecture ppt 05 on quality documentation. You will have to
come up with your own reason/objective and your source of
recombinant protein that you will be detecting for your
Western. The protein that you are detecting can be from a
bacteria, yeast, any plant, any animal, human, etc. You are all
expected to work on different proteins. Also do a google search
for a vendor/source of antibodies to detect your protein. 4-
5pages.
Video 1:
https://www.youtube.com/watch?v=EDi_n_0NiF4
Video 2:
https://www.youtube.com/watch?v=eaETFKXtNRA
Video 3:
https://www.youtube.com/watch?v=VgAuZ6dBOfs
Western Blotting
MaterialsTransfer Buffer
750 ml of H2O
100 ml of 10X SDS-PAGE buffer
150 ml of MeOHPBS-Tween

20. 895 ml of H2O
100 ml of 10X PBS
5 ml of 10% TweenBlocking Buffer
50 ml of PBS-Tween
2.5 g of Carnation Dry MilkDry Gel
Solution
385 ml of H2O
200 ml of MeOH
30 ml of 50% glycerol
1. Run protein gel @ 120 – 160 mV.
Standard Marker: 2 l of Perfect Protein Western Marker
(Novagen #69959)
or ECL protein molecular weight markers (Amersham #
RPN2107)
2. Set up for blotting
1) Cut out a membrane (Immobilon-P) square that will fit gel.
2) Soak membrane in MeOH for 1 min. and then immerse in
H2O.
3) Place the membrane in transfer buffer for more than 15 min.
4) Put the blotting gel box in the container filled with transfer

21. buffer, add two sponges to the box, and then place a piece of
filter paper onto the sponges (Make sure both are completely
wet in the transfer buffer).
5) Remove the gel from running apparatus using spatula with
sharp edge.
6) Slice a bit of the gel lane edges and place the gel onto the
filter paper on the box (Make sure no air bubbles are between
gel and paper!).
7) Place the soaked membrane (from step 3) onto the gel, again
making sure there are no air bubbles between the gel and
membrane.
8) Place a filter paper onto the membrane, making sure no air
bubbles are between paper and membrane.
9) Place two sponges and lid, put these blotting sandwich into
the gel box.
10) Fill the box entirely with transfer buffer (If the box is
leaking, the apparatus is not assembled correctly).
11) For transferring, run the blot at 30 volts for 2.5 hours.
3. Binding the antibody
1) Slice the membrane around the gel using a razor blade in
order to minimize area of membrane that is to be probed with
antibodies and stained, when protein is finished transferring.
2) Incubate the membrane in dry milk blocking buffer with

22. shaking for one hour at room temperature or overnight at 4C.
3) Put 2 l of S-Protein HRP conjugate (Novagen #69047) and 5 l
of anti-FLAG M2 Monoclonal Antibody (Sigma # F3165) into
10 ml of SuperBlockBlocking Buffer in PBS (PIERCE #37515).
4) Place the membrane in heat sealable bag and pour this
solution, seal the bag (be sure to cool seals of bag down) and
incubate for one hour for nutating.
5) Wash membrane 3 times for 15 minutes each with PBS-
Tween on shaker.
6) Mix 2 l of Anti-mouse Ig-HRP linked whole antibody (from
Sheep) (Amersham #NA931) and 2 l of S-Protein HRP
conjugate with 10 ml of dry milk blocking buffer.
7) Place membrane in heat-sealable bag and add the antibody
solution. Seal bag, being careful not to allow antibody solution
to touch recently sealed edges.
8) Incubate one hour on shaker.
4. Developing the blot
1) Wash membrane 3 times for 15 minutes each with PBS-
Tween on shaker.
2) Mix 4 ml of solution A with 100 l of solution B (ECL Plus
Westernblotting Detection Reagent, Amersham # RPN2132).
3) Place membrane on a piece of parafilm (protein side up), add
the staining solution to the membrane and gently tilt it to ensure
protein is covered in solution.

23. 4) Cover the membrane in foil and incubate for 4 minutes.
5) Wrap membrane in plastic bag and place it in the film box.
6) Take this to the dark room and burn the film for 5 minutes, or
as much time as would give a good signal.
7) Slide the film through the developer to develop.