MicroNIR: soluzioni QbD e PAT

Transcription

1 MicroNIR: soluzioni QbD e PAT Milano, 8 Maggio 2018 Emiliano Genorini MicroNIR EMEA & India Account Manager (office) (mobile) Via Torri Bianche, , Vimercate (MB) - Italy 1

2 Company profile 2

3 Company Profile - Viavi Solutions 3

4 Our vision 4

5 MicroNIR - Our vision 5

6 MicroNIR - Our vision 6

7 MicroNIR - Our vision

8 Linear Variable Filter 8

9 Product line - LVF LVF is mounted directly over a photodiode detector array Polychromatic light illuminates the linear variable filter (LVF) The wavelength transmitted through the filter is dependent on its linear position along the filter Each pixel detects a specific wavelength of light 9

10 Product line - LVF No moving parts: - no misalignments - stability over long time - 100% transferability between units No fiber optics: - no possibility to break it - no aging - insensible to temperature fluctuation Small distance high energy and S/N from traditional benchtop to sensor 10

11 Granulation and drying 11

12 MicroNIR - Granulation and drying On Line measurement Temperature No sampling Physical measurement Indirect moisture analysis At Line measurements Moisture (Karl Fischer or LOD) Sampling required Chemical measurements Direct moisture analysis Lab measurement 12

13 MicroNIR - Granulation and drying NIR Spectroscopy is also a USP method <1119> Widespread acceptance in the pharma industry At line, online and in-line techniques Data collected in seconds No laboratory skilled personnel required Not destructive 13

14 MicroNIR - Granulation and drying Welded flange 14

15 MicroNIR - MicroNIR - Granulation and drying Extened Probe 15

16 MicroNIR - Granulation and drying RMSECV = 0.52% RMSEP = 1.10 % Verification shown good predictability 16

17 MicroNIR - Granulation and drying Batch 1 High shear granualtion + bottom spary drying 3 batches Start and end LOD similar Batch 2 Batch 3 17

18 MicroNIR - Granulation and drying? End point 18

19 MicroNIR - Granulation and drying Process trajectory Batch 2 Batch 1 Batch 3 Process trajectory Batch 1 and 3 similar trajectory Batch 2 is different and not easy at all to spot 19

20 MicroNIR - Granulation and drying Granules growthing 20

21 Blending 21

22 MicroNIR - Blending The tablet development and manufacturing process and focus on the critical role that blending plays in the making of a quality tablet A tablet might need to be quick to dissolve in your body but it also must not break up in its packaging when transported So, if you make them hard to withstand transport they probable don't dissolve easily, if you make them friable in order to dissolve quickly they fall apart in the packaging and customers complain 22

23 MicroNIR - Blending Labor intensive Expensive Poor reproducibility Blender must be stopped Perturbation of blending Long time to have feed back Contributes to sample non-uniformity Cross contamination Using of solvents Potential for exposure of operators to high potency API 23

24 MicroNIR - Blending 24

25 MicroNIR - Blending Rotation Time API concentration Excipients Particle Size Blender Capacity Rotation Rate Fill level Loading Method (symmetric vs. asymmetric) 25

26 MicroNIR - Blending 26

27 MicroNIR - Blending Optimize Integration Time. Define blender Rotation Speed. Effective Scan Time Sensor Inactive Zone Delay Time Determine where powder completely covers sampling window, determine Delay Time. Calculate time from start of delay to where sensor switch turns off. The Scan Count is calculated as the Effective Scan Time divided by the Integration Time. 27

28 MicroNIR - Blending Problem Blend Model Blend

29 MicroNIR - Blending Liter Bin 10 Liter Bin Liter Bin Rotation Number % Filll 75% Filll 90% Filll rpm 25 rpm 32 rpm Rotation Number Active Layered - Centered 0.03 Active Spot - Off Center Rotation Number 29

30 MicroNIR - Blending End Point Change of the 1 st PC score from negative to positive indicates blending uniformity is reached after ~ 350 rotation 30

31 MicroNIR - Blending End Point Change of the 1 st PC indicates blending uniformity is reached after ~ 350 rotation 31

32 Feed frame 32

33 MicroNIR - Feed frame MicroNIR on top feed frame using existing viewing windows Probe height adjusted by micrometer ( mm) Acquisition can be continued or triggered based (external trigger set on paddle) Feed frame assembly taken out of tablet press for test and in line verification 33

34 MicroNIR - Feed frame 34

35 MicroNIR - Feed frame 35

36 Tablet Compression 36

37 MicroNIR - Tablet Compression MicroNIR mounted in enclosure Tablets centered on MicroNIR Window 37

38 MicroNIR - Tablet Compression 4 development blends + 1 production blend + 1 placebo blend Proposed plan allowe evaluation of: Model accuracy Model linearity NIR & Method robustness Total ammount of samples to analyze using reference methods 17 38

39 MicroNIR - Tablet Compression 39

40 MicroNIR - Tablet Compression 40

41 MicroNIR - Tablet Compression 41

42 MicroNIR - Tablet Compression 42

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