July 5, 2022

Role of Balances and LIMS in Data Integrity“Does your company's electronic balance support data integrity?”
In recent years, we have been receiving more and more inquiries similar to the above quote. In thepharmaceutical industry, there is an increased need for ensuring data integrity for the safety and quality ofpharmaceutical products. Since mass is extremely important data that is typically measured first in ananalysis, it is naturally subject to data integrity.
However, data integrity usually cannot be complete with just balance data by itself. Comprehensive data
management is required, including measurement results from other instruments such as GC, HPLC, andICP.
We will now introduce how to ensure data integrity by connecting A&D's balances to YOKOGAWA'sLaboratory Information Management System (LIMS), OpreX LIMS, which supports quality management
operations.

What is Data Integrity?
According to the FDA (U.S. Food and Drug Administration) definition*1, data integrity "refers to thecompleteness, consistency, and accuracy of data", and "complete, consistent, and accurate data should
be attributable, legible, contemporaneously recorded, original or a true copy, and accurate” (i.e., inaccordance with ALCOA principles).
Due to a number of data falsification and fraud findings during GxP inspections, regulatory authorities suchas the FDA, MHRA (UK Medicines and Healthcare Products Regulatory Agency), PIC/S (Pharmaceutical
Inspection Cooperative Scheme and Cooperative Agreement on Drugs), and WHO (World HealthOrganization) have been strengthening their monitoring of data integrity. Accordingly, guidance on data
integrity has been issued one after another by various regulatory authorities.

*1 2018, ‘Data Integrity and Compliance With Drug CGMP Questions and Answers Guidance for Industry’, p. 4

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ALCOA+
Each guidance adopts the basic principles of data integrity, "ALCOA+". ALCOA+ is an extension of thetraditional ALCOA and consists of the following items.
Attributable

The creator of the data must be clear.

LegibleData must be readable and understandable for anyone.

Contemporaneous

Data must be measured and recorded at the same time.

Originality

Copied data must be the same as the original data.

Accurate

Results and data must be accurate and free of errors.

CompleteAll necessary information to reconstruct events must be available.

Consistent

Data must be consistent and without contradictions.

Enduring

Data must be extant for the duration of the data retention period.

Available

Data must be accessible so that the data can be reviewed at any time during
the data retention period.

Trying to fulfill these requirements manually or on paper not only requires a great deal of time and effort,
but also invites the risk of human error, such as transcription errors, omissions, calculation errors, and lossof data, which in turn leads to poor data integrity. In addition, as mentioned above, data from otherinstruments add to the scope and complexity. Therefore, in order to efficiently and holistically manage alldata inputs in a centralized manner, a dedicated electronic system such as OpreX LIMS is highly
recommended.

OpreX Laboratory Information Management System (OpreX LIMS)
This section covers some of the solutions offered by OpreX LIMS when connecting to balances andensuring data integrity. For more information on this system, please contact Yokogawa ElectricCorporation.
Using OpreX LIMS with a balance is quite simple as the balance is only required to output massmeasurement data while OpreX LIMS handles the processes necessary to ensure data integrity. Users
are just advised to verify by the IQ (Installation Qualification) of the balance in the initial setup that there
are no problems with the balance's performance and that the values displayed on the balance match thevalues entered into OpreX LIMS.

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A balance can be connected to OpreX LIMS by converting its RS-232C to Ethernet (TCP/IP) signals using
a protocol converter.*2 The LAS (Laboratory Automation System) will then automatically collect data fromvarious instruments, including balances. This saves on the labor spent on manual data entry and prevents
transcription errors and falsification of data.

OpreX LIMS
Ethernet (TCP/IP)
RS-232C - Protocol Converter

Balance

HPLC

GC

OthersLAS (Laboratory Automation System)

In addition, the following solutions help ensure data integrity.
Regulatory compliance by security, tracking and traceability features
By entering user IDs and passwords when logging on, approving, or making changes, etc., securesystem operation can be achieved by setting appropriate permissions for each user.
OpreX LIMS has also Audit Trail and Change History Reference capabilities, such as an Operation
History log, which tracks the reception, input, approval, and judgment of data, Data Movement log aswell as System log.

Paperless operation and improved search speed
The primarily online nature of OpreX LIMS means that operations are paperless. Test results data canbe input online. The review, approval, and pass/fail determination of test result data are all also
conducted online.
In addition, a database of various types of data is compiled which facilitates and speeds up data
searching, comparison with other samples and past data, and trend analysis. It can also be utilized
for product quality verification.

*2 For details on connection methods, please contact Yokogawa Electric Corporation.

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Calibration management of analytical instruments
OpreX LIMS can also manage and maintain calibration records, calibration deadlines, and calibration
histories for connected analytical instruments, balances, etc.

Conformance to regulations for electronic records and signatures
In terms of management of electronic record and signature, OpreX LIMS conforms to FDA 21 CFRPart 11, ER/ES guidelines, and PIC/S GMP Guidelines.

Summary
Various issues related to data integrity required in the pharmaceutical industry can be solved by centrally
managing data from balances and various analytical instruments with LIMS. A&D's balances have a
proven track record of connecting to YOKOGAWA's OpreX LIMS. For users who have not introduced a
LIMS yet, we can recommend OpreX LIMS with confidence.

Point of Contact
Balances and Weight & Measurement Solutions
A&D Company, Limited
www.aandd. jpOpreX LIMS and Data Integrity Solutions
Yokogawa Electric Corporationwww.yokogawa.com