Quality by design detailed ppt.

1. A Seminar On
Quality By Design(QbD)
Presented By:
Mr. Balu .S . Khandare
M. Pharm(PQA) Sem I
Roll No.523
Guided By:
Mr. P.B. Dudhe
(Assistant Professor)
Sinhgad College of Pharmacy, Vadgaon(Bk.), Pune-411041.
2017-2018
10-09-2018 1

2. Mr.BaluS.Khandare
 Content
Introduction
What is Quality by Design (QbD) ?
Approach
Element of QbD
Research paper
Case study
Reference
10-09-2018 2

3. Mr.BaluS.Khandare
 Introduction
“Quality by Design” (QbD) is a next step of “Quality by Testing” (QbT) which is
the comprehensive approach targeting all phases of pharmaceutical framework
which offers operational tractability with ultimate aim of improving value added
process rather than the cost added of medicines for the consumer.
10-09-2018 Ref. Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9. 3

4. ICH Guideline
ICH Q8 Pharmaceutical Development (2006)
ICH Q9 Quality Risk Management ( June 2006)
ICH Q10 Pharmaceutical Quality Systems (April 2009)
ICH Q11 Development & Manufacture of Drug Substances
(May 2012)
Product
Design
Process
Design
Manufacturing
Process
Monitoring/
Continuous
Verification
10-09-2018 Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9 4
Mr.BaluS.Khandare

5. Mr.BaluS.Khandare
 What is Quality by Design (QbD) ?
QbD is:
 A Quality system for managing a product lifecycle .
 A regulatory expectation .
 Intended to increase process and product understanding and thereby decrease
patient risk .
“Quality cannot be tested into products,
it should be built in, or by design.”
10-09-2018 Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9. 5

6. Mr.BaluS.Khandare
 Approaches to Pharmaceutical Development
10-09-2018 Ref. Lawrence, X.Y., 2008. Pharmaceutical quality by design: product and process development, understanding, and control. Pharmaceutical research, 25(4),
pp.781-791.
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7. Mr.BaluS.Khandare
 Element of QbD
Quality Target Product Profile (QTPP)
Critical Quality Attributes (CQAs)
Risk assessment
Design space
Control strategy
Life cycle management
Process Analytical Technology (PAT)
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8. Mr.BaluS.Khandare
 Understanding QbD
Target Product
Profile (TPP)
Early Product
Development
QTPP
Process
Development
Control
Strategy
Technology
Transfer
Process Risk
Assessment
Conformance
Manufacturing
Continued
Process
Verification
10-09-2018
Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9.
8

9.  Quality Target Product Profile (QTPP)
• A summary of the drug development program described in terms
of labeling concepts and it mainly focus on the safety and efficacy.
• This is related to identity, assay, dosage form, purity, stability in
the label For e.g. salbutamol sulphate tablet.
Table 1: Quality Target Product Profile for Salbutamol
Sulphate Tablet
Sr. no. QTPP Element Target
1 Dosage form Tablet
2 Dosage design Conventional release tablet
3 Route of administration Oral
4 Dosage strength 4mg
5 Pharmacokinetics Conventional release
enabling Tmax in 15-20
minutes or less
6 Shelf life 36 month
Ref. Bhitre, M.J., Ingale, A.V. and Mene, R.A., International Journal for Pharmaceutical Research Scholars (IJPRS).10-09-2018 9
Mr.BaluS.Khandare

10. Mr.BaluS.Khandare
 Critical Quality Attributes (CQAs)
A property or characteristics that when controlled within a defined limit , range ,
or distribution ensures the desired product quality.
Potential CQAs are derived from the QTPP and guide product and process
development.
CQAs are identified by quality risk management and experimentation to
determine the effect of variation on product quality.
TPP QTPP CQAs
10-09-2018
Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4,
pp.13-9. 10

11. Mr.BaluS.Khandare
 Conti…
The CQAs list can be dynamic and may be updated based on product and process
knowledge.
Critical Material Attributes (CMAs) that are independent of each other provide
specific goals with which to evaluate a mfg. process.
For Ex.A dissolution test may depend on particle size and hardness.
Some physicochemical and biological properties like , pH ,ionic strength
,dissolution ,particle size , globule size of emulsions ,etc.
10-09-2018
Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9.
11

12. Mr.BaluS.Khandare
 Risk Assessment
 It is important to provide a systematic risk analysis of how raw materials, process
steps and process parameters affect product quality.
One of the points to consider in risk assessment ,is to provide an explanation when
citing prior experience as the basis for assigning risk.
A risk assessment also is important for effective communication between FDA and
industry and for intra company communication (such as between research /
development and manufacturing and among multiple manufacturing sites).
10-09-2018 Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9. 12

13. Mixing
Over mixing
Resulting in de
mixing or
segregation of the
materials
Wet granulation
Binder concentration is less
Granulating solution require and more
time require to dry
Binder conc. more
Affects the uniformity of granules.
Drying rate
Affect flow
Compression
Force of compression
Hardness
Affects the
disintegration
and
dissolution of
tablets.
10-09-2018
Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9.
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Ex.
Mr.BaluS.Khandare

14. Mr.BaluS.Khandare
 Design Space
Design space as defined by the FDA is “The multidimensional combination and
interaction of input variables (e.g. material attributes ) and process parameters that
have been demonstrated to provide assurance of product quality’’.
To study the effects of different formulations and / or process variables or to
determine the best levels of excipients that provide optimal drug release or
dissolution properties.
10-09-2018 Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9. 14

15. Mr.BaluS.Khandare
 Control Strategy
 A planned set of controls , derived from current product and process
understanding that ensures process performance and product quality .
The controls can include parameters and attributes related to drug substance and
drug –product materials and components, facility and equipment operating
conditions, in –process controls, finished –product specifications ,and the
associated methods and frequency of monitoring and control.
10-09-2018 Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9. 15

16. Mr.BaluS.Khandare
10-09-2018
Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9
16

17. Mr.BaluS.Khandare
 Life Cycle Management
Once the product is approved , CQAs need to be monitored continuously to ensure
that the process is performing within the defined acceptable variability that served
as the basis for the field design space.
Any changes to the design space itself need to be characterized, validated and
approved by the regulatory authorities prior to implementation.
10-09-2018 Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9 17

18. Mr.BaluS.Khandare
 Process Analytical Technology (PAT)
Defined as ‘’a system for designing , analysing , and controlling manufacturing
through timely measurements(i.e., during processing) of critical quality and
performance attributes of raw and in-process materials and processes, with the
goal of ensuring final product quality’’.
Traditional
approach
PAT
approach
10-09-2018 Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9. 18

19. PAT in Tablet manufacturing
Stage Technique Measurement
Dispensing NIR Identification of raw materials
Wet Granulation NIR Moisture distribution
Drying NIR Moisture content
Blending NIR Blend Uniformity
Compression
Strain gauges Compression force
NIR Content Uniformity
10-09-2018 Ref . Patil, A.S. and Pethe , A.M., 2013. Quality by Design (QbD): A new concept for development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9. 19
Mr.BaluS.Khandare

20. Mr.BaluS.Khandare
 Downstream processing from hot-melt extrusion
towards tablets: a quality by design approach
 Materials
• Soluplus® (SOL) was selected for this study as amorphous polymer and
Celecoxib , a BCS class II drug, was used as model drug.
Method
• Hot-melt extrusion
• HME experiments were performed using a co-rotating, fully intermeshing twin-
screw extruder .
10-09-2018
Ref . Grymonpré, W., Bostijn, N., Van Herck, S., Verstraete, G., Vanhoorne, V., Nuhn, L., Rombouts, P., De Beer, T., Remon, J.P. and Vervaet, C., 2017. Downstream processing from hot-melt extrusion
towards tablets: A quality by design approach. International Journal of Pharmaceutics, 531(1), pp.235-245.
20

21. Mr.BaluS.Khandare
 Preparation of tablets
 Direct compression.
Tablets of approximately 270 mg were produced at 3 main compaction pressures:
127 ( ±9.1), 255 (±19.2) and 382 ( ±27.0) MPa at a turret speed of 5 rpm without
using a pre-compression step.
Design of experiments
The experimental ranges for the DOE factors barrel temperature, screw speed ,
throughput and drug load were determined based on preliminary experiments.
10-09-2018
Ref . Grymonpré, W., Bostijn, N., Van Herck, S., Verstraete, G., Vanhoorne, V., Nuhn, L., Rombouts, P., De Beer, T., Remon, J.P. and Vervaet, C., 2017. Downstream processing from hot-melt extrusion
towards tablets: A quality by design approach. International Journal of Pharmaceutics, 531(1), pp.235-245.
21

22. Mr.BaluS.Khandare
 Conti…
 A two-level full factorial design with 16 experiments was applied to evaluate the
influence of process parameters: barrel temperature (160-200 °C), screw speed
(50-200 rpm) and one formulation parameter: drug load (0-20 %) on the HME
process and tableting behaviour of the resulting extrudates.
10-09-2018
Ref . Grymonpré, W., Bostijn, N., Van Herck, S., Verstraete, G., Vanhoorne, V., Nuhn, L., Rombouts, P., De Beer, T., Remon, J.P. and Vervaet, C., 2017. Downstream processing from hot-
melt extrusion towards tablets: A quality by design approach. International Journal of Pharmaceutics, 531(1), pp.235-245.
22

23. Mr.BaluS.Khandare
 Evaluation of the HME process
At each extrusion condition, the torque on the screws was recorded after reaching
steady state conditions and the specific mechanical energy (SME) calculated to
evaluate the HME process.
1. Thermal analysis
2. Particle size analysis
3. Moisture content
4. Flowability
10-09-2018
Ref . Grymonpré, W., Bostijn, N., Van Herck, S., Verstraete, G., Vanhoorne, V., Nuhn, L., Rombouts, P., De Beer, T., Remon, J.P. and Vervaet, C., 2017. Downstream processing from
hot-melt extrusion towards tablets: A quality by design approach. International Journal of Pharmaceutics, 531(1), pp.235-245.
23

24. Mr.BaluS.Khandare
 Conti…
10-09-2018
Ref . Grymonpré, W., Bostijn, N., Van Herck, S., Verstraete, G., Vanhoorne, V., Nuhn, L., Rombouts, P., De Beer, T., Remon, J.P. and Vervaet, C., 2017. Downstream processing from hot-melt extrusion towards
tablets: A quality by design approach. International Journal of Pharmaceutics, 531(1), pp.235-245.
24

25. Mr.BaluS.Khandare
 Conclusions
A QbD approach for HME/tableting was successfully implemented in this
research study to evaluate the influence of process parameters and drug load
during HME on both extrudate properties and tableting behaviour of an
amorphous solid dispersion formulation.
Increasing drug loads resulted in compacts with higher tensile strength since the
volume reduction mechanisms changed towards more fragmentary behaviour
combined with more plastic deformation and less out-of-die elastic recovery.
10-09-2018
Ref . Grymonpré, W., Bostijn, N., Van Herck, S., Verstraete, G., Vanhoorne, V., Nuhn, L., Rombouts, P., De Beer, T., Remon, J.P. and Vervaet, C., 2017. Downstream processing from hot-melt extrusion towards
tablets: A quality by design approach. International Journal of Pharmaceutics, 531(1), pp.235-245.
25

26. Mr.BaluS.Khandare
 A useful strategy based on chromatographic data combined with
Quality-by-Design approach for food analysis applications. The
case study of furanic derivatives in sugarcane honey.
A QbD approach applied to analytical method development is based on a few key
steps.
Starting with the analytical target profile (ATP) and resulting in the definition of a
method operable design region.
 QbD concept in food analysis seems to be a promising strategy to provide
assurance of quality of the analytical data and harmonization of methods.
10-09-2018
Ref . Silva, P., Silva, C.L., Perestrelo, R., Nunes, F.M. and Câmara, J.S., 2017. A useful strategy based on chromatographic data combined with quality-by-design approach for food analysis applications. The
case study of furanic derivatives in sugarcane honey. Journal of Chromatography A, 1520, pp.117-126
26

27. Mr.BaluS.Khandare
 Materials and methods
Samples, standards, reagents and materials .
• Commercial SCH and sugarcane juice (SCJ) samples were supplied by the
traditional producer stored under stable conditions (4 °C, in the dark).
• FDs standards, 5-hydroxymethyl-2-furaldehyde (5HMF), 2furaldehyde (FURL),
2-furylmethanol (FAL), 2-furyl methyl ketone (2FMK) and 5-methyl-
2furaldehyde (5MF), and the solvents/eluents formic acid (FA), acetonitrile (ACN)
and methanol (MeOH),Ultrapure deionized water (H2Od), was used throughout
the study.
10-09-2018 Ref . Silva, P., Silva, C.L., Perestrelo, R., Nunes, F.M. and Câmara, J.S., 2017. A useful strategy based on chromatographic data combined with quality-by-design approach for food
analysis applications. The case study of furanic derivatives in sugarcane honey. Journal of Chromatography A, 1520, pp.117-126.
27

28. Mr.BaluS.Khandare
 Conti…
 All solvents and samples were filtered through 0.22 µm membrane filters.
 UHPLC analytical columns, CORTECS C18 (1.6 µm, 2.1 × 100 mm), ACQUITY
BEH C18 (1.7 µm, 2.1 × 50 mm), ACQUITY HSS T3 (1.8 µm, 2.1 × 100 mm)
and the VANGUARD pre-column (1.6 µm, 2.1 × 5 mm).
10-09-2018
Ref . Silva, P., Silva, C.L., Perestrelo, R., Nunes, F.M. and Câmara, J.S., 2017. A useful strategy based on chromatographic data combined with quality-by-design approach for food analysis applications. The case
study of furanic derivatives in sugarcane honey. Journal of Chromatography A, 1520, pp.117-126. 28

29. Mr.BaluS.Khandare
 Samples and standards solutions preparation
Working solutions of lower concentration with all FDs standards were daily
prepared, by appropriate dilution, with H2O : MeOH (95:5% v/v) solution
acidified with 0.1% FA.
FDs standard stock solutions (1000 mgL−1) were prepared by dissolving
appropriate amounts of the compounds in MeOH, and stored at - 20 °C, in the
dark, till analysis.
Samples were prepared using 10 g of SCH in 20 mL of H2O :MeOH (95:5% v/v)
acidified with 0.1% FA and stored (4 °C, in the dark).
10-09-2018 Ref . Silva, P., Silva, C.L., Perestrelo, R., Nunes, F.M. and Câmara, J.S., 2017. A useful strategy based on chromatographic data combined with quality-by-design approach for food analysis applications. The
case study of furanic derivatives in sugarcane honey. Journal of Chromatography A, 1520, pp.117-126.
29

30. Mr.BaluS.Khandare
 UHPLC-PDA conditions
The separation and identification of FDs was carried out on a UHPLC-PDA
ACQUITY system.
The binary mobile phase was composed by acidified H2O(0.1% FA, eluent A) and
ACN (eluent B), with a constant flow rate at 125 µL min-¹.
The 15 min gradient was as follows: 95% A (0 min); 80% A (1 min); 75% A (2
min); 70% A (5 min); 20% A (8 min); and 95% A (15 min).
 The column temperature was kept at 50 ºC and the sample manager at 20 ºC. The
injection volume was set at 10 µL. and the detection wavelength was set at 275
nm.
10-09-2018 Ref . Silva, P., Silva, C.L., Perestrelo, R., Nunes, F.M. and Câmara, J.S., 2017. A useful strategy based on chromatographic data combined with quality-by-design approach for food analysis applications. The case
study of furanic derivatives in sugarcane honey. Journal of Chromatography A, 1520, pp.117-126.
30

31. Mr.BaluS.Khandare
 Statistical software
All data analysis and modeling processing were performed using the STATSOFT
STATISTICA 12.0 (2013) software (Tulsa, USA).
• According to the results, all
sorbents were suitable to extract
all FDs under study
10-09-2018 Ref . Silva, P., Silva, C.L., Perestrelo, R., Nunes, F.M. and Câmara, J.S., 2017. A useful strategy based on chromatographic data combined with quality-by-design approach for food analysis applications. The case study of furanic
derivatives in sugarcane honey. Journal of Chromatography A, 1520, pp.117-126.
31
Fig .2

32. Mr.BaluS.Khandare
 Conclusions
In this work an ultrafast and robust MEPSR-CX/UHPLC CORTECS-PDA
analytical method combined with QbD approach for FDs profiling in complex
sugary matrices was successfully developed.
 Compared with conventional extraction techniques, MEPS was simpler, faster,
efficient and an environmental-friendly procedure as it requires small amounts of
organic solvents.
10-09-2018 Ref . Silva, P., Silva, C.L., Perestrelo, R., Nunes, F.M. and Câmara, J.S., 2017. A useful strategy based on chromatographic data combined with quality-by-design approach for food analysis applications. The
case study of furanic derivatives in sugarcane honey. Journal of Chromatography A, 1520, pp.117-126.
32

33. Mr.BaluS.Khandare
 References
• Patil, A.S. and Pethe, A.M., 2013. Quality by Design (QbD): A new concept for
development of quality pharmaceuticals. Int J Qual Assur, 4, pp.13-9.
• Grymonpré, W., Bostijn, N., Van Herck, S., Verstraete, G., Vanhoorne, V., Nuhn,
L., Rombouts, P., De Beer, T., Remon, J.P. and Vervaet, C., 2017. Downstream
processing from hot-melt extrusion towards tablets: A quality by design
approach. International Journal of Pharmaceutics, 531(1), pp.235-245.
• Bhitre M.J. , Implementation of Quality by Design to the Process Validation with
Risk-Based Approach for Quality Assurance of Salbutamol Sulphate Tablets ,
“International Journal for Pharmaceutical Research Scholars(IJPRS)” , V-2 (2013)
P-176-18610-09-2018 33

34. Mr.BaluS.Khandare
• Silva, P., Silva, C.L., Perestrelo, R., Nunes, F.M. and Câmara, J.S., 2017. A useful
strategy based on chromatographic data combined with quality-by-design
approach for food analysis applications. The case study of furanic derivatives in
sugarcane honey. Journal of Chromatography A, 1520, pp.117-126.
• Antonelli, A., Chinnici, F. and Masino, F., 2004. Heat-induced chemical
modification of grape must as related to its concentration during the production of
traditional balsamic vinegar: a preliminary approach. Food Chemistry, 88(1),
pp.63-68.
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35. Thank You
Save the environment …..Go green!!!
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