Agilent 280-DS Mechanical
Qualification System for Dissolution
Apparatus 1 and 2

A User-friendly System with Software Built for 21 CFRpart 11 ComplianceTechnical OverviewAuthors

Introduction

Vinayak A.K and Dan Spisak

The debate for the periodic qualification procedure of dissolution apparatus 1 and 2
began long ago. The United States Pharmacopeia (USP) recommends the Performance
Verification Test (PVT) using Prednisone, while the US Food and Drug Administration(FDA) endorses an enhanced mechanical qualification (eMQ) regimen, citing FDA andASTM eMQ procedures1. The FDA recommends performing the enhanced MQ as analternative for PVT2,3. Close monitoring of the dissolution system significantly improves
the quality of the dissolution results, and is required for either procedure. Recent
reports show that the purely mechanical option is receiving more attention, and morelaboratories are switching to eMQ4. Since the FDA guidance made this procedure
an official alternative in January 2010, eMQ has been a sound approach for periodic
qualification. Although it removes the need for chemical testing with Prednisone,
it can still be time-consuming if multiple manual tools are used to measure thephysical parameters of apparatus 1 and 2. Additionally, the ability to read small analog
scales, when placed down in the vessel, may lead to possible misinterpretation ofmeasurements.

Agilent Technologies, Inc.

The Agilent 280-DS Mechanical
Qualification System (MQS) can overcome
many of the traditional problems faced
when performing MQ. It includes user
friendly hardware and software designed
to enable 21 CFR Part 11 compliance.
This enables fast and accurate physicalparameter measurements in a regulatedenvironment. The use of advanced
optical sensing technology in the designof 280-DS MQS makes the system very
accurate and precise, providing real-timemeasurements and communication. The
intuitive Agilent 280-DS Workstation
software guides the user step-by-stepthrough each parameter of the methodthat may be customized for user-specificrequirements. This software is designed
to meet the stringent guidelines of21-CFR-Part 11, ensuring data integrity
and security, which is essential in thecurrent GMP environment.

DesignThe 280-DS MQS consists of two primarymodules, the Vessel module (VM) andInstrument module (IM) (Figure 1). The
VM measures rotational speed, basket
and shaft wobble, vessel/shaft centering,shaft verticality, vessel verticality, andbasket/paddle height. The IM measuresvessel plate level and vibration while also
acting as a hub for a temperature probe,
the VM, and connectivity to the PC. The
measurement of each physical parameteris designed based on the requirements of
the harmonized pharmacopeias (USP, EP,JP) as well as the FDA/ASTM enhanced
mechanical calibration procedure (MQ).

AAgilent 280-DS Vessel ModuleBasket wobble
sensor

Vesselverticality
sensorBHeight lever
RPM sensor

Agilent 280-DS Instrument Module

Temperatureprobe plug-in

Vessel plate leveland vibration sensors

Vesselcenteringsensors(upper)
Vesseldiameterarm
Vesselcenteringsensors(lower)

Vessel module
plug-inUSB plug-in

Height Arm

Figure 1. The two main modules of Agilent 280-DS MQS: vessel module (A) and instrument module (B),showing the parts, connection ports, and sensors associated with it.

Setup
For efficient communication, allmodules are initially connected to theWindows‑based PC or laptop where thesoftware is installed. These connections
enable the system to respond quickly,
resulting in real-time recording ofmeasurements. Once communication
is established, the user may access the280-DS Workstation software by entering
the appropriate login credentials. The
first step is to input the configuration
details of the dissolution apparatus.
This includes manufacturer, system
identification, as well as individual serial
numbers for all relevant accessories(for example, paddles and baskets).
Agilent/Varian/VanKel instruments
may be connected directly, allowing
the instrument configuration details

2

to be automatically downloaded. Oncethese details have been completed, themethod editor tool is used to create thedesired method based on user‑specified
requirements. An appropriate methodname is then entered to properly identify
the procedure to be executed. Preloaded
mechanical specifications and tolerances
matching the ASTM and FDA procedures
may be selected, or a unique sequencewith custom tolerances can be definedaccording to the user need.
Once the instrument configuration
or method files are created, they caneasily be recalled for future use; it is
not necessary to create them for every
qualification. Any changes to the initialfiles are documented and completely
traceable using the built-in revisionhistory and audit trail features of thesoftware.

Operation
The 280-DS Workstation software
prompts the user to select the method
and apparatus for the desired test.
Depending upon which USP apparatus
is installed, the user can select shaft
type (paddle or basket), and specify theactive positions to be measured. Before
starting the test, the software allows theuser to review the selected parameters
and tolerances one more time. Afterconfirming the method, the test sequenceis initiated. The user is then guided
through a series of steps with graphicaland text assistance (Figure 2).

Once the appropriate module iscorrectly positioned (as instructedby the software), the user may direct
his/her attention to the PC as the opticalsensors and internal gauges do all thework. This not only simplifies the entire
measurement process, but introduces
an unmatched level of repeatability
when using this device. Measurements
are free from visual interpretation, andquantifiable data are generated in aconsistent manner from test to test.
Every measurement will have AS FOUND
values, which display the current online
readings of the respective test parameter.
The user can monitor each parameterand view any out-of-specification results

Magnetic clip

A
587

6

1234

during the test. Appropriate comments
can be added to provide further
explanation whenever necessary; theseare documented, and appear on the final
report.
At the end of the test, a completion
message is displayed and the user canupdate the qualification due date at thattime. If an error occurs during the test
sequence, the user is able to cancel thetest, but only after providing a reason thatis documented for compliance purposes.
The software will generate the final
report after completing the tests, which
is automatically stored in the securedatabase. This report can also be printed
or exported as a PDF.

B

To measure shaft wobble, ensure that the paddle is in its operating position within Vessel 1, andthat the paddle clears the bottom of the vessel module body. Place the magnetic clip on the shaft,aligning it with the rpm detector. Program the dissolution apparatus with the selected rotational
speed, then initiate spindle rotation. Click Run when ready.

Figure 2. The 280-DS software displays text and graphics to guide the user through each parameter measurement.

3

Data Review
The 280-DS Workstation software makes
searching for historical data easy. The
user can review the final data extensively
and apply various filters (for example,
date range, instrument ID, operator,laboratory, or report status) to customize
the desired information and reports. The
report filter capabilities are especially
useful in an audit situation if specificdata from an instrument or date range arerequired.
All information about the test is
documented in the report including
dissolution apparatus information, test
parameters measured, tolerances, andfinal results (that is, Pass/Fail) (Figure 3).

The software allows the user to sign the
document electronically once the review
is completed. All reports can be exported
to other locations as different file formats.
All historical data can be analyzed forpatterns using the exclusive trending
function of the software. This powerfulfeature allows for potential problems
or issues to be identified and resolved
prior to becoming an out-of-specification
result. For example, if a particular basket
wobble has increased (but not yet failed)over the past three measurements, thisbasket can be replaced or adjustments tothe apparatus may be made. The trending
feature can also provide meaningful data
for a particular position as part of aninternal failure investigation.

Figure 3. Features of the Agilent 280-DS eMQ report.

4Time Savings
The 280-DS MQS greatly reduces the time
it takes to acquire the measurements
compared to individual, manual tools.
To proceed through the ASTM or FDA
MQ procedures takes about 15 minutes
for paddles or baskets. Although theapparatus may be thoroughly evaluatedevery six months, the goal of eMQ is tomaintain the apparatus in top condition.
The FDA and ASTM procedures require
laboratories to establish the frequencyof each mechanical measurement.
The 280‑DS allows the laboratory tomeasure physical parameters more often,
perhaps weekly or monthly, to ensure
greater apparatus integrity, and prevent
potential failures or the need for massive
failure investigations. The speed-of-use
allows the 280-DS to perform faster
qualifications, and provide valuable
information needed for daily, routine
situations in a matter of only minutes.

User-friendly Features of theAgilent 280-DS MQSThe 280-DS MQS is a device that
improves the integrity of individual
measurements over manual gauges usedin traditional MQ measurements. Table 1
summarizes these key features and theiradvantages.
Table 1. Key features of the Agilent 280-DS MQS.
FeatureAdvantage

The Agilent 280-DS MQS is compatible with all dissolution apparatus withspace between the drive unit and vessel plate.

Use the same measurement tool on various brands of dissolutioninstrumentation, not just Agilent.

The software can control Agilent, Varian, or VanKel apparatus using an
RS‑232 cable.

Eliminates the need to activate spindle rotation for RPM, Wobble or Vibration
measurements (Figure 4A). The connection also enables the Agilent 280-DS to
download the serial and identification number of these apparatus.

Once properly positioned, the Agilent 280-DS does all the work – providing
reliable, repeatable measurements using innovative sensing technology.

Measurements are the same regardless of user reducing variability andimproving consistency as well as efficiency.

Quantitative values for each parameter are recorded and visible in real timeusing the software interface.

No more interpretation of manual gauges. Plus, real-time feedback gives
the user the ability to optimize conditions of the instrument and make any
adjustments required.

Sturdy and compact design of both the Agilent 280-DS Instrument and Vesselmodules.

Protects the measuring components securely to provide a robust and reliablesystem.

Includes a custom, insulated carrying case.

Provides secure transport and storage of the Agilent 280-DS components(Figure 4B).

Agilent 280-DS workstation software has preloaded enhanced MQ parameters Quick setup and execution of tests meeting FDA or ASTM Procedures.
and tolerances based on regulatory requirements.
Alternatively, the user can include custom parameters and tolerances to meetinternal requirements (Figure 5).
Records for every Agilent 280-DS test can be viewed using various filtering
criteria to simplify customized reports.

Easily recall data specific to an apparatus, date range, and so forth. This isespecially useful for laboratory audits.

Trending feature of Agilent 280-DS Workstation software provides a useful tool Allows the user to monitor the measurements of specific parameters over time
to monitor performance of individual parameters for each position (Figure 6).
and find/resolve issues before they fall out of specification(s).
A

B

RS232

Figure 4. A) Image showing the connectivity of the Agilent 280-DS workstation software to an
Agilent 708‑DS Dissolution apparatus. B) An Agilent 280-DS MQS in a custom, insulated carrying case.

5

Figure 5. Customizing feature allows selection of specific parameters from ASTM, FDA, or USP Toolkit procedures.

Figure 6. Example of trending feature for RPM measurements.

6

21 CFR Part 11 ComplianceFeatures of Agilent 280-DS MQSAPart 11 of Title 21 of the Code of FederalRegulations (CFR) is for electronic records
and electronic signatures, and applies
to records in electronic form that arecreated, modified, maintained, archived,retrieved, or transmitted4. Some of therequirements of compliance are listed
below with the matching feature (shownin figures) in the 280-DS Workstation
software.

••User access (Figures 7A and 7B):
For 21 CFR Part 11 compliancepurposes, the Dissolution
Workstation software uses
Windows features to ensure that(a) access is limited to authorizedindividuals, (b) no two individuals
have the same combination ofuser identification and password,(c) passwords are periodicallychecked, recalled, or revised,and (d) transaction safeguards toprevent unauthorized use of user
IDs or passwords are implemented.

B

Figure 7. A) Screenshot showing user access. B) Restriction to unauthorizedaccess by locking the application.

A

Secure, computer-generated,time-stamped audit trails: To
independently record the date
and time of operator entries
and actions that create, store,or modify electronic records.
Changes to electronic records do
not obscure previously recorded
information (Figure 8).

BC

Figure 8. A) Security audit trial window showing operator entries and calendar-based filters for retrieving
records. B) Pop-up window when the user makes any changes or updates to the method. C) Reportshowing summarized details and a comparison of two versions of the same method.

7•Signature manifestations:
Signed electronic records contain
information associated with thesigning that clearly indicates
all of the following: the printedname of the signer, the date andtime when the signature wasexecuted, and the meaning (suchas review, approval, responsibility,or authorship) associated with thesignature (Figure 9).

•Review of test reports: The
software maintains the complete
history for all tests executed on the280-DS system, which satisfies thefollowing technical requirementsof 21 CFR Part 11: (a) ability togenerate accurate and complete
copies of records in both humanreadable and electronic form
suitable for inspection, review,and copying by the agency and(b) protection of records to enable
their accurate and timely retrievalthroughout the record retention
period (Figure 10).

Figure 9. Display of electronic signature

AB

Figure 10. A) Reporting feature showing the various filters users can apply for retrieving reports. Information about test status, method, serial number, laboratory,and operator are displayed. B) Recording feature showing individual serial number of the shaft and place to attach the certificate associated with the shaft.

8Conclusion

References

The Agilent 280-DS MQS with
Agilent 280-DS Workstation software isan efficient and trouble-free mechanicalqualification tool for USP dissolution
apparatus 1 (baskets) and 2 (paddles).
The features of this system are based on
two important qualities: user-friendlinessand compliance. With the time reductionof the entire mechanical qualification
process to approximately 30 minutes,
all while improving the accuracy andquality of measurement, the 280-DS
adds an unprecedented level of integrity
to dissolution testing. By incorporating
optical sensing technology for datameasurement, the guesswork andvariability in measurement is eliminated,
thereby improving results, and truly
redefining dissolution qualification.

1. Agilent technologies practicalsolutions newsletter Volume 11, issue
1 http://www.agilent.com/cs/library/periodicals/public/5991-0073ENUS_low_res.pdf
2. Redefining Dissolution Qualification– An in depth Examination of theUSP PVT and the ramificationsof moving to a fully mechanicalqualification, Agilent Technologies
LCGC Whitepaper, publication number5991-6754EN.
3. FIP Position Paper on Qualificationof Paddle and Basket Dissolution
Apparatus, AAPS http://www.
ncbi.nlm.nih.gov/pmc/articles/
PMC2802143/pdf/12249_2009_
Article_9291.pdf
4. Proper Implementation ofEnhanced Mechanical Calibrationof Dissolution Apparatus 1 and 2,
Agilent Technologies, publication
number 5990-9866EN, May 1, 2012.

9www.agilent.com/chem
This information is subject to change without notice.
© Agilent Technologies, Inc., 2016
Published in the USA, July 1, 2016
5991-7007EN