pharmaceuticals

3. Qualification of Dissolution
Testers: USP Performance
Verification Test (PVT)
Dr. Yasir Mehmood
Pharm-D. MBA, MPHIL, Ph.D. (Pharmaceutics)
Head of QA & VIRAC
Over 12 years of experience in Quality System, Quality Operations, Stability
Studies, Regularity Compliance & Teaching. Services in Pharmaceuticals,
Nutraceuticals, Herbal Preparations & Teaching.
SaffronPharmaceuticals (Pvt.) Ltd.
19 Km. Sheikhupura Road, Faisalabad-Pakistan.
One Day Training Session

4. Outline
USP <711> Dissolution-
Apparatus 1 and 2
Identifying and Controlling
Sources of Variability
Qualification of Dissolution
Testers
Performance Verification Test
(PVT)
01
02
03
04

5. 50
02
To evaluate the drug product performance during
manufacturing
90
04
To link performance of drug product on market
with the batch used for bioavailability studies
20
01
To aid confirming potential benefits or identifying issues
due to changes in formulation or processing during
drug product development
75
03
To detect variations in the manufacturing process
which have critical influence on the dosage form
performance
Goals for Dissolution

6. Vessels
• Glass or other inert, transparent material
• Cylindrical with hemispherical bottom
• 1L,2L or 4L nominal capacity
Basket
• 40 mesh (wire openings of 0.36-0.44
mm)
• Gold coating of 2.5 µm is allowed
Stirring
• Rotating Stirrer
• Typical speed: 50-100 rpm
Dosage form Placed in the
basket
USP Apparatus 1 - Basket

7. USP Apparatus 2
- Paddle
Vessels
Same as apparatus 1
Stirring blade and shaft
• Metallic or suitable inert and rigid
• May be coated
Stirring
• Rotating Stirrer
• Typical speed: 50-100 rpm

8. Sources of variability
For an integrated dissolution testing
system in general, the sources of
variability in results may come from
The dissolution testing apparatus that generates the test
solutions – including its environment
1.
The devices used for
– Sampling
– Processing
• Filtration • Dilution • Transfer
2.
3.
4.
6.
5.
The details of the testing procedure
The analytical instruments and method used to
quantify the dissolved drug substance in the test
solution
The analyst
The specimen under investigation and its intrinsic
variability

9. Computational Fluid Dynamic (CFD) in USP App. 2
Velocity magnitudes
in different regions of the
vessel at 50 rpm

10. 01 The collection of documented evidence that an
instrument performs suitably for its intended purpose
and according to USP General Chapter <1058>, is a
four part process
02 Generally addressed by the equipment manufacture by
designing dissolution equipment and/or parts that will
meet the specifications described in USP General
Chapter <711>: Dissolution
03 Help to satisfy the Operational Qualification (OQ) and
parts of Installation Qualification (IQ)
Types of Qualification
Analytical Instrument Qualification (AIQ)
Design Qualification (DQ)
Mechanical Qualification

11. 11
1
Design
Qualification (DQ)
2
Installation
Qualification (DQ)
4 Performance
Qualification (PQ)
3
Operational
Qualification (OQ)
Analytical Instrument Qualification (AIQ)

12. Performance
verification test
(PVT)
Satisfies the Performance
Qualification (PQ) portion of
AIQ and provides evidence that
the dissolution equipment is
functioning properly

13. Complete method /covers IQ,
OQ, PQ Metrology aspects:
Ability to uncover the influence
of unforeseen system variables
in dissolution testing
PVT involves system suitability testing
by prednisone, a validated reference
standard tablet with pre-established
testing characteristics
PVT covers mechanical,
chemical, and analytical parts of
dissolution testing and not just the
mechanical part
PVT involves system suitability testing
by prednisone, a probe, designed and
developed by USP for this specific use
Ability to compare intra/inter
lab variation
PVT is a globally recognized
method for dissolution system
suitability
WhyisPVTa USPrequirement?

14. PVT Informational Brochure, Whitepaper, Podcasts, Instrument Qualification Instructional Videos
and more available:
https://www.usp.org/chemical-medicines/pvt
PVT Resources areavailable

15. USP Prednisone
Tablets RS
Certificate

16. Media Deaeration
How an appropriate
volume of the medium to
between 41°C and 45° C.
Vacuum filter through a
0.45-µm membrane filter
(HVLP type, or equivalent)

17. Other deaeration procedures are permissible. For testing with USP Prednisolone Tablet RS, an O2
level of not more than about 6ppm is acceptable
Deaeration Procedure
%
Prednisone
dissolved
Oxygen Conc. Mg/L
Effect of dissolved oxygen concentration on percent prednisolone dissolved in 30min.

18. Basket
Place one tablet in each dry
basket.
Attach the basket to their
shafts
Immediately start the
stirring

19. Timing
The starting procedure
must allow for sample
collection and filtration
within the current +-
2%tolerance limit
A staggered start may be
used, allowing a minimal
start-time interval between
vessels and is
recommended if possible

20. Peddles
Allow the tablet to fall into
vessel in a standardized
manner.
The test is considered to
start when the tablet comes
to rest at the bottom of the
vessel
Immediately start the
stirring

21. Sampling
Withdraw a portion of
medium from each vessel,
about 30ml.
Sample from the zone
midway between the
surface of the medium and
the top of the basket or
peddle blade, not less than
1cm from the vessel wall

22. Filtration
Filter each sample
immediately through a
syringe filter (0.45µm
PDVF-type or equivalent)
discarding the first 5ml of
filtrate
Discarded volume is a
function of the filter and
may not be identical to that
recommended in these
guidlines

23. Large collaborative study (multiple international
participants, including equipment manufacturers,
regulatory agencies, and pharmaceutical manufacturing and
testing laboratories)
=Acceptance limits based on statistical analysis from
collaborative study
– Range of acceptable geometric means
– Acceptable upper limit of within-laboratory CV of all individual
results
BOTH MUST PASS
ISO-based Acceptance Criteria
– two-sided limits on the mean
– one-sided limit (upper bound) on the %CV
Setting Specifications
for the PVT

24. Acceptance Criteria

25. Calculation Tool
Example

26. 26
Troubleshooting
Data that fails the Geometric Mean requirement
(high) but passes the %CV requirement usually
indicates that something is affecting all
positions of the dissolution tester in a similar
manner
 Lack of proper degassing
 External source(s) of energy/vibration
 Bias introduced by (automated) sampling
and/or analysis procedures
 Errors from the standard solution’s
absorptivity value
Data that fails the %CV requirement usually
indicates an issue with one or more of the
individual positions
 Using mixed vessels
 Localized source(s) of energy/vibration
 Issues with specific components
I failed my PVT, now what?

27. Recommendations for a successful PVT and for consistent
dissolution results
Follow the procedure described in the Certificate
of the Reference Standard
Designated vessel and shaft for each position in
dissolution instrument
Rigorous mechanical qualification & Proper de-
aeration of dissolution medium
Test should be started as soon as possible after
media de-aeration & Filter samples immediately
after withdrawing samples from vessel

28. Questions?

29. THANK YOU