Frequently Asked Questions

March, 2024
Keywords or phrases:
FDA, 21 CFR Part 11, Software, FAQ, GxP

Octet® BLI 21 CFR Part 11 Software Frequently
Asked Questions (FAQ)
Stuart Knowling, Ph.D, Sartorius, Fremont, CA
Correspondence
E-Mail: octet@sartorius.com

IntroductionGxP Compliance Tools for Octet® BLI Systems
From antibody quantitation, ligand binding characterization to potency assays, Sartorius offers a wide range of GxP compliancetools for developing validated assay methods on the Octet® BLI platform, including: Comprehensive tools for GxP compliance Simplicity in operations for analytical development and regulated quality control labs
Availability of a comprehensive tool set for compliance makes the Octet® BLI platform an ideal analytical instrument in regulated
quality control (QC) labs for lot release and in-process testing for ligand binding, concentration, and impurity analysis in both
upstream and downstream processes.

Sartorius Solutions for GxP Compliance
Compliant Installation and Operational Qualification (IQ/
OQ) Kit and Services
The IQ/OQ kit provides comprehensive documentation to
verify the Octet® BLI instrument, accessories and computer
system are supplied and installed per Sartorius’s guidelines
by certified personnel. It also provides documented
verification that the Octet® BLI instrument operates as
intended at the user site by inspecting the criticalcomponents. These tests verify that the various key
operational parameters, such as the optical system, plate
temperature, system alignment, lamp performance, andshaker speed meet stipulated specifications.
Performance Qualification (PQ) Kits
PQ kits provide rapid and convenient methods to verify theperformance of your Octet® R8 and RH16 systems. PQ canbe performed using one or two tightly controlled assays,
depending on the instrument’s intended use. The PQKinetics and quantitation assays verify accuracy andprecision of the assays are within specifications for a wellcharacterized model system pair.

2Octet® CFR Software and Software Validation Package
For researchers working in GLP or GMP laboratories, theOctet® Software Validation Package provides the mostcomprehensive documentation and tools available tovalidate the Octet® GxP server Monitor and Octet® CFR
Software features and functions. It trims validation time tojust three days using a fully integrated manual that mirrors
the validation process in a regulated laboratory andprovides sample data sets to authenticate analysis within
Octet® software to traditional programs including
Microsoft® Excel, and GraphPad Prism.
Biosensor Validation
This service enables Octet® BLI system users to sample
multiple lots of a biosensor during assay qualification andvalidation and reserve a well-characterized lot for purchase.
The service is available for the following biosensor types:
Octet® ProA, Octet® SA, Octet® SAX, Octet® NTA, andOctet® AMC. Customers can order up to five different
biosensor lots, up to 20 trays from each lot for evaluation,and reserve up to 40 additional trays for future purchase.

Software and Compliance – Frequently Asked Questions
1. How is the Octet® GxP software package different fromthe regular Octet® BLI software?
The Octet® 21 CFR Part 11 Software package includes allfeatures available in the regular Octet® BLI Discovery andOctet® Analysis Studio software package but Octet® 21
CFR Part 11 Software has features to allow users to produce
electronic records that meet the requirements of the FDA
21 CFR Part 11 Final Rule. This includes features such asadministratively controlled application access, user groupwith defined access and roles, an audit trail, and electronic
signatures of artifacts.
All Octet® R-Series BLI systems can use the Octet® 21 CFRPart 11 software package with basic Installation Qualification
and Operational Qualification (IQ/OQ) and Performance
Qualification (PQ). However, the Octet® R8 and Octet®
RH16 (beginning SN 20325+) systems are better suited
for a GxP environment due to the availability of extended
IQ/OQ, and PQ packages that add more tests anddocumentation to verify the functioning of the systems and
QC assay kits that generate automatic reports in the Octet®
Analysis Studio Software.
2. Is the Octet® CFR software package compatible with
Windows 10?
Yes, Octet® CFR Software versions 10 and above arecompatible with Windows 10 32-bit and 64-bit beginningwith Windows 10 version 1607, the “Anniversary Update.”
Windows 10 versions 1507 and 1511 are not supported. We
recommend Windows 10 64-bit Professional or Enterprise.
Windows 7 is no longer supported. Octet® Software version
13 is also compatible with Windows 11.
3. Is it possible to install the software on a terminal serveror remote desktop server if users cannot install theapplications on individual workstations ?
For Octet® BLI Discovery Software when recording data,
the files should be stored to the local computer and afterrecording, the files can then be moved to a network drivefor backup. The Octet® Analysis Studio Software can beinstalled on a server or workstation and then users canremote desktop to it.
4. How many user accounts can be registered on an GxPserver?
There are no enforced limits. The practical limit is the space
available on the computer hard drive.
5. How are detailed histories recorded on the GxP server?
Audit trails are recorded in the database managed by the
Octet® GxP server software. Each experiment has a unique
identifier, and all data-specific audit trails are logged withthe experiment identifier. Audit trails can be filtered byexperiment, user, machine, project or date for viewing andprinting.
6. Can Octet® BLI data be integrated onto Watson LIMS?
We currently don’t formally integrate with any LIMS
systems. Depending on how your system works, you could
potentially upload Excel, CSV or PDF reports created by the
analysis software. If the LIMS allows arbitrary file upload/
attaching, you could archive method files and even raw data
as well.
7. Can you turn off specific feature(s) of the 21 CFR Part 11
software?
21 CFR Part 11 features cannot be disabled. However, a user
with the permission “Set commenting requirement” (see“Viewing and Changing Group Settings” in Octet® BLI
Discovery User Guide 13) – can disable the commenting
requirement in the Octet® Analysis Studio Software. All
activities will still be logged to the audit trail, but this turns
off the “enter reason” dialog that pops up whenever achange is made.
8. Is it possible to install the Non-21 CFR Part 11 softwareon the same PC as the 21 CFR Part 11 software?
Yes, it is possible, but this is not recommended as acompliance best practice.
9. Can an audit trail be Deleted? If so, will that leave a
trace in the GxP server?
Specific entries in the audit trail cannot be deleted by anymeans in the Octet® software.
Uninstall/reinstall also does not delete the audit trail. If you
really need to delete the entire audit trail, you can do so if
you are an IT administrator on the computer running the
GxP server. It is important note here is that here that
“Administrator” refers to the Administrator to the PC(Windows PC), not the GxP server. Only the IT administrator
can delete the audit trail database and there is no scheme
for the GxP server administrator to delete the audit trail file.
The location of the file is provided in our documentation as
it is desirable to create backups of the audit trail database.
This is also why it is recommended that the GxP server isinstalled on a separate computer from those running theOctet® BLI Discovery or Analysis Studio Software, thisensures that IT can safeguard any accidental deletion of theaudit trail files.
Each organization must develop controlled, documented
procedures for compliance with this requirement. It is thecustomer’s responsibility to administrate these documents.
310. What are the allowed user privileges?
The following default group selections are available, and ingeneral (Table 1):
 Administrators—can manage Users and Group settings
including add, delete, edit and view all events
 Supervisors—can review data and events
 Developers—can create methods, run experiments, adjust
analysis settings, and export data Lab Users—can run experiments, view and export data Guests—have no explicit privileges, these must be
assigned by the administrator

11. How can we authenticate Excel workbooks?
Octet® Analysis Studio Software generates a passwordprotected excel report sheets in which cells are protected
and cannot be changed. However, in general we don’t
provide a means to authenticate Excel workbooks. Onceyou export data to Excel you are outside of our CFR
umbrella of data integrity. Sartorius does not consider this adata integrity defect.

See Octet® BLI Discovery User Guide 13 for more
information on user privileges.

Default Group Privileges
Administrator

Supervisor

Developer

Lab UserGuest

Lab User

Guest

Administration
Manage users and user settings

Yes

Analysis and Change
Create and edit method template

Yes

Build multi-dataset

Yes

Edit preprocess settings

Yes

Edit analysis settings

Yes

Edit annotation/display properties

Yes

Convert Kinetic step/step type into Quantitation

Yes

Edit report pages

Yes(LEGACY) Change

Yes

Review
Sign Document

Yes

Set commenting requirement

Yes

Review Audit Trail for any user

Yes

Remove signature from document
Default Group Privileges (continued)
Administrator

Supervisor

Developer

Plate Settings
Edit experiment info

Yes

Edit sensor and sample plate info

Yes

Include/exclude wells and sensors from analysis

Yes(LEGACY) Plate

Yes

Run Experiment
Run Experiment

Yes

Import analysis settings template to new dataset

Yes

Export data and Excel report

Yes

Choose repository directory when running anexperiment

Table 1. Default User Privileges.

412. Are the audit trails on the GxP server, Octet® BLI
Discovery, and Octet® Analysis Studio software linked?
How is the audit trail saved after the user logs out fromthe GxP software?
Yes, the audit trails are all stored on a single database that
the GxP server manages (Figure 1). Therefore, the server
location must be chosen when logging into either theOctet® BLI Discovery or Octet® Analysis Studio software.
During login, you can use the Project setting (when loggingin) to link experiments in the audit trail, and you can also
sort/filter by experiment ID when reviewing the audit trail.

Figure 1. Project selection is possible when starting a user session.

13. We currently have an older version of the Octet® CFR
software in our development group and have released
assays using the older version; When we purchase thenew version of the software (version 13), do we need tore-qualify released assays? What is different between ourold version and version 13?
You would need to re-validate the assay using the newsoftware to ensure that the method under the new softwareis still fit for purpose. Please refer to version 13 software
release notes for “what has changed”.
It is important to note that after upgrading to GxP server
v13.0, do not downgrade to a previous version of GxP serveras there is a risk of data loss. Always make a backup of thedatabase files before performing an update to the GxPserver software.
14. What happens if the customer (an administrator or any
other group member) forgets the password to access thesoftware?
Users and administrators cannot see an existing password.
If a user forgets their password, the administrator cannot
recover the lost password. The only solution is for theadministrator to set a new password for the user.
A potential problem occurs when as administrator forgets
their password as an administrator cannot reset their own
password without first entering the old password. If theadministrator loses their own password, then resetting the
password is not possible. For this reason, we recommend
storing a written copy of the password in a secure location
and/or assigning a second person with administrator
privileges so that if one administrator password is forgotten,
the other administrator can reset the password.
15. Are the server and server administration pre-installedin the computer when purchasing the instrument with
the CFR software? If not, who is responsible for doing
this?
The Octet® CFR software and GxP server softwareare not pre-installed. Sartorius FAS/FSE will install thesoftware upon installation. If the customer purchased
GxP packages (Octet® R8, RH16, and RH96 systems),
these packages would also include IQ/OQ services that
direct and document the software’s installation. Since
GxP server setup and configuration will require customer
IT and QA support, the installation of the software should
be coordinated with the respective customer teams
beforehand. IT usually advises on server configurations(GxP server locations), and QA/IT will inform of company
password and administrator policies established at thecustomer site.
16. How are the changes registered when the Octet® 21
CFR part 11 software is not connected to the server?
If a computer cannot connect to the GxP server, user
activity is recorded and stored locally. When the computerre-establishes a connection with the GxP server, the local
stored events are uploaded to the GxP server audit log
database. In addition, if a user tries to log in to the Octet®
software on a computer that cannot connect to the GxPserver, the software will use a temporary local token toauthenticate their identity. This token is created during
the first successful login to Octet® Analysis Studio or
BLI Discovery. The token is good for 5 days and can berefreshed by reconnecting with the GxP server. If a user
is traveling and would like to use the Analysis Studio towork on their data, for example, it is possible to set up a
VPN so they can periodically connect to the GxP server.
Administrator can change this setting (e.g., number of days
to “0”) to prevent offline use (Figure 2).

Figure 2. Offline usage can be allowed or prevented in the Constants tab.

5

Network Configuration
17. Can only administrators have access to the server andgrant privileges?
Any user can log into the GxP server administration tool.
Non-administrators can see the various settings, but they
can only edit their name and change their password. Allother settings are locked (see Q5 on user privileges).

Recommended Configuration®
®
or theQuality
Control
the Octet
GxP
Installthe Octet
GxPdepartment.
Server onto a dedicatedadministrator
computer.
Thisserver
can be a dedicated phy®
workstation, or a virtual machine. Typically, the Octet GxP Server computer will be under local IT coinstallation media to prevent the setup of “rogue” GxP
that the server is always on and available for client connections. The Octet® hardware controller PC m
serverinstances.
work
connectivity
to the Octet® GxP Server. Other optional workstations with the Octet® Analysis St
will also need network connectivity to the Octet® GxP Server.

18. How is the transition from non-CFR software to CFR
software? Can customers do their own installation using adownloadable link?
Octet® CFR software can be installed on an Octet® BLI
system that does not currently use Octet® CFR software.
Sartorius FAS/FSE will need to guide you through thevalidation process. We strongly recommend that nonCFR software should be uninstalled as an Octet® systemvalidated for CFR compliance should not use softwarethat does not check the permissions set in the GxP server
software.

19. Can customers access the software if they do not have Figure 3: Network layout.
Figure B-1: Network layout
the privileges to run experiments or analyse data?
Yes, depending on their assigned privileges, they can use
Decide in advance how the client applications will find the server instance. If you use the IP address d
Option 2: Single
Computeror use a DHCP
reservationConfiguration
for the Octet® GxP Server computer. Most corporate ne
Octet® BLI Discovery and Analysis Studio Software. A user static IP address
Installation of the Octet® GxP Server Modulethefully qualified
name (FQDN) of thenetwork
server.
Ifassigned
you cannot
use domain
the recommended
configuration,with no explicit privileges is a Guest and can only open,
install the Octet® GxP server software on a single computer
view, and print data and method files.
Single Computer Configuration
along with the Octet® BLI Discovery software (Figure 4).
If you cannot use the recommended network configuration, install the Octet® GxP Server software oThis
is awith
last
puter
along
theresort.
Octet® BLI Discovery software. This is a last resort.
20. What happens if an experimental file is modified?
See the following section for compliance considerations if using this option.
Modification of files outside the Octet® BLI softwareenvironment will cause the data integrity checks to fail.
There is no recovery process.
21. Regarding the software installation, which option isrecommended?
There are two options available to users:
Option 1: Recommended Configuration
Install the Octet® GxP server onto a dedicatedadministrator computer (Figure 3). This can be a dedicatedphysical server workstation, or a virtual machine. Typically,
the Octet® GxP server computer will be under local IT
control. Ensure that the server is always on and available
for client connections. The Octet® hardware controller PC
must have network connectivity to the Octet® GxP server.
Other optional workstations with the Octet® Analysis Studiosoftware, will also need network connectivity to the Octet®
GxP server.
It is important that users ensure compliance. The Octet®
GxP server is a key part of keeping records compliance.
Strictly control the access to the computer hosting theOctet® GxP server software. Any Windows accounts that
are Administrators on the server can directly access theuser and audit trail databases to backup work. Place theserver under the control of a department separate from the
day-to-day users of the Octet® system, for example local IT,
63011602 B

Octet® BLI Discovery User Guide®
iguLayoutre B-2: Layout
a single computer
computer with with
the Octet
systemFigureF4:of aofsingle
theOctet® system.

Ensuring Compliance

The Octet® GxP Server is a key part of keeping records compliance. Strictly control the acc

IMPORTANT:
If you are using the Single Computering the Octet® GxP Server software. Any Windows accounts that are Administrators on theaccess the user
and audit trail
databases
to backup
work.
Place the server under the contr
Configuration,
configuretheWindowsuser
accounts®
rate fromthe day-to-day users of the Octet® system, for example local IT, or the Quality desystemusers as Windows standard accounts.
for Octet
GxP Server
installation media
to prevent theControl the Octet
Any Windowsuser®with
Administrative
privileges
onsetup of “rogue” GxP Serv®
the computer
will
have
accessto theOctetConfiguration,
GxP server
IMPORTANT:
If youare usingthe Single
Computerconfigure the Windows
Octet®
system users as Windows standard accounts. Any Windows user with Administrativ
database
files.
®
puter will have access to the Octet GxP Server database files.

Installation of the Octet® GxP Server Module

NOTICE: If you are upgrading from an earlier version of Octet® GxP Server, make a backup
files before proceeding. See “Backup the Database” on page 564.
1.

Navigate to the window that lists the files on the installation CD.

2.

Double-click OctetGxPServer.exe to launch the installer.

Systems and Services – Frequently Asked Questions
22. Are the Octet® R2, R4, RH16, and RH96 also GxP compliant and if so what IQ/OQ products do we use withthem?
Yes, all Octet® BLI systems are GxP compliant (Figure 5).
They are all compatible with Octet® 21 CFR Part 11 software.
Each system has its own separate IQ/OQ guideline.
All Octet® R-Series BLI systems can use the Octet® 21 CFRPart 11 software package with basic Installation qualification
and Operational Qualification (IQ/OQ) and Performance
Qualification (PQ), but the Octet® R8 and Octet® RH16
(beginning SN 20325+) are better suited for a GxPenvironment due to the availability of extended IQ/OQ, andPQ packages that add more tests and documentation to
verify the functioning of the systems and QC assays kitsthat generate automatic reports in the Octet® Analysis
Studio Software.
23. After IQ/OQ, what services are recommended bysartorius on an annual basis to maintain the system?
After installation and initial Operational Qualification (OQ),
Instrument Preventive Maintenance (PM), andPerformance Qualification (PQ), currently available only on
the Octet® R8 and Octet® RH16 BLI systems arerecommended on a planned/scheduled service interval as
it removes the risk of the system and software being out ofspecification (OOS).

24. Does Sartorius offer an extended service for the GxPenvironment and what is handed over to the customer toverify that the service was performed according to GxPrules?
GxP customers can request a Performance Certification(PC) service or PMOQ service. A PMOQ service includes aPreventive Maintenance (PM) service with operational
qualification (OQ) tests for a specific instrument type. In thecase of the Octet® R8 and Octet® RH16 BLI systems, it also
includes the Performance Qualification – Quantitation (PQQ) assay in addition to the two Performance Qualification –Kinetics (OQ-K) assays (see Figure 5).
25. How is the temperature of the plate determined forthe systems other than Octet® R8 and Octet® RH16 BLI
Systems? Is there an internal measurement of
temperature?
During the assembly process, the heater plate temperature
is verified to be within a window of 32.8 – 33. 2°C. The plate’s
temperature is controlled using closed loop temperature
controllers. The temperature is verified at manufacturing
and during system preventative maintenance (PM) andPerformance Certification (PC) described in question 24. A
record of the value is created during PC.
26. How is the RPM of the shaker determined?
Shaker speed is controlled using a closed control loop that
ensures that the shaker is operating within range. The
shaker speed and % error is stipulated by the shaker
manufacturer and is verified through a diagnostic softwaretool available on the system. Verification is done atPreventive Maintenance (PM) and during Performance
Certification (PC). A record of the value is created.

Model

Octet® R2

Octet® R4

Octet® R8

Octet® RH16*

Octet® RH96

GxP option

Yes

Yes

Yes

Yes

Yes

IQ/OQ Kit

41-032741-0326

41-0325

41-0285

41-0217

IQ/OQ Service

84QAFR2

84QAFR4

84QAFR884QAF16

84QAF96

PQ Service

N.A.

N.A.

84QFFR8

84QBF16

N.A.

2x PMOQ Service

84MCFR2

Performance Qualification N.A.
Bundle Kit

84MCFR484MCFR884MBF16

84MBF96

N.A.

18-1178

18-5140

N.A.

*beginning SN 20325+

7

Assays and Method Development – Frequently Asked Questions
27. What key parameters need to be demonstrated in a
GxP assay during method qualification?
These parameters are assay dependent and should follow
regulatory requirements for the assay type. The
determination of such parameters is the responsibility ofthe sponsor. Users interested in assay validation guidelinesthat can be used to develop well-qualified assays should
see the Application Note Harmonizing Regulatory
Guidelines for Assay Validation: A Focus on Kinetics-Based
Assays Using Octet® BLI Systems.
28. What type of assays is Octet® BLI currently utilized forin QC?
The Octet® BLI platform is used mainly for lot release andin-process testing assays. These are typically quantitation,
potency assays, impurities testing or ligand binding assays.
29. Is BLI technology used in a current GxP compliant
release process approved by the FDA?
There are several groups using the Octet® BLI platform for
lot release assays. Organizations tend to keep certain
information confidential and as a result, it may be difficult topoint out specific accounts without their permission. The“Octet® BLI Characterization Data Used for Approved
Drugs” table on the next page gives examples of cases in
the public domain where Octet® BLI has been used togenerate supporting data for regulatory submission ofvarious products (Table 2).

830. How do we measure potency using the Octet® BLI?
What are the reportable parameters?
Please see the Application Note Octet® Potency Assay:
Development and Validation Strategies.
Reportable parameters should be established by thesponsor but generally include % recovery and % CVs. KD(Affinity) values can also be reported depending on thetype of the method.
31. What is the accepted % CVs for a kinetics assay?
% CVs and other acceptance criteria are productdependent and should be set by the sponsor. Users
interested in assay validation guidelines that can be used todevelop well-qualified assays should see the Application
Note Harmonizing Regulatory Guidelines for Assay
Validation: A Focus on Kinetics-Based Assays Using Octet®
BLI Systems.

Drug Name

TargetDrug Modality

SponsorRegulatory
AgencyKeytruda | Pembrolizumab

PD-1

mAb

Merck

Tecentriq | Atezolizumab

PD-L1

mAb

Comirnaty | BNT162b2

COVID-19

Ultomiris | Ravulizumab

Year of
Approval

Indications

Application

EMA

Non-small celllung cancer

Affinity
Characterization

2015

Roche

EMA

Non-small celllung cancer

Specificity

2017

mRNA Vaccine

Pfizer

EMA

COVID-19

Affinity
Characterization

2020

Human C5mAb

Alexion

EMA

Paroxysmal
nocturnal
hemoglobinuria(PNH)

Affinity
Characterization

2019

Livogiva | Teriparatide

PTH

PeptideBiosimilar

Teva

EMA

Osteoporosis

Affinity
Characterization

2020

Atoltivimab, maftivimab,
and odesivimab-ebgn

EBOV
glycoprotein

mAb Cocktail

Regeneron

FDA

Ebola virus

Competition studies

2020

Oyavas | Bevacizumab

VEGF-AmAb Biosimilar

Mabxience

EMA

Non-small celllung cancer

Specificity | Affinity
Characterization

2021

Jemperli | Dostarlimab

PD-1

mAb

GSK

EMA

Endometrial
cancerAffinity
Characterization

2021

Regdanvimab

S proteinmAb

Celltrion

EMA

COVID-19

Affinity
Characterization|
Blocking Assay

2021

Xevudy | Sotrovimab

S proteinmAb

GSK | Vir
EMA
Biotechnology

COVID-19

Affinity
Characterization

2021

Nuvaxovid

COVID-19

VaccineNovavax

EMA

COVID-19

Affinity
Characterization

2022

Kimmtrak | Tebentafusp

CD3 | gp100 TCR

Immunocore

EMA

Uveal
Specificity
melanoma (UM)2022

Tixagevimab | Cilgavimab

COVID-19

mAb
Combination

AstraZeneca

FDA

COVID-19

Affinity
Characterization|
Blocking Assay

2022

Opdualag (nivolumab |relatlimab)

LAG-3 |PD-1

mAb
Combination

BMS

EMA

Melanoma

Blocking Assay

2022

Table 2. Examples of approved drugs utilizing Octet® BLI data in their applications. This table includes examples of drugs where the Octet® BLI system
has been used to generate data submitted as part of the supporting information for the drug’s approval with regulatory bodies.

9Germany
Sartorius Lab Instruments GmbH & Co. KG
Otto-Brenner-Strasse 20
37079 Goettingen
Phone +49 551 308 0F or further contacts, visit
www.sartorius.com

Specifications subject to change without notice.
Copyright Sartorius Lab Instruments GmbH & Co. KG.
Octet-BLI-21-CFR-Part-11-FAQs-en-Sartorius
Status: 03 | 2024 Rev A

USA
Sartorius Corporation
565 Johnson Avenue
Bohemia, NY 11716
Phone +1 631 254 4249
Toll-free +1 800 635 2906