Quality by Design and Expertise: Accelerating time to market of complex oral solid dosage forms

Transcription

1 CPhI Worldwide 2017 October 24 th -v 26 th, 2017 Frankfurt Quality by Design and Expertise: Accelerating time to market of complex oral solid dosage forms Lucile KOWALSKI - NPI Project Manager Guy VERGNAULT - VP R&D

2 Skyepharma provides de-risked time- and cost-effective services Time and Cost Efficiency Extensive project management Right First Time Development Early stage development Commercial & packaging

3 A Right First Time approach creates competitive services 1. Patient-oriented, Quality by Design approach 2. Cost reduction and enhanced time-tomarket 3

4 Quality by Design is the Gold standard Material attributes (MA) 2. Do they have an impact on a CQA? Quality Target Product Profile (QTPP) QbD Process Patient : quality, safety, efficacy 1. Quality attributes : Which ones are critical? CQA Process parameters (PP) 3. To what extent do they impact a CQA?

5 QbD : Pros and Cons Operational flexibility Process robustness Reduction of IPC PROS Requires investment Time Raw materials Specific skills CONS

6 Case study : To what extent do CPPs impact a CQA? (1/2) Implementation of design of experiment Responses Case study: impact of 5 factors and their interactions on crushing strength Pressure Pressure Final pressure 9.50 Turret speed Dose strength

7 Case study : To what extent do CPPs impact a CQA? (2/2) Implementation of design of experiment Turret speed, rpm Leading science-driven development Crushing strength (N) a Dose strength, mg c

8 QbD : Pros and Cons Operational flexibility Process robustness Reduction of IPC PROS Time Raw materials Specific skills CONS

9 QbD : Pros and Cons Operational flexibility Process robustness Reduction of IPC PROS Time Raw materials Specific skills CONS

10 QbD : Pros and Cons Operational flexibility Process robustness Reduction of IPC PROS Time Raw materials Specific skills CONS

11 QbD : Pros and Cons Time Raw materials Operational flexibility Specific skills CONS Process robustness Reduction of IPC PROS

12 Case study 2 : Do PPs have an impact on a CQA? Compression pressure on disso mg of API day Feeding shoe settings on hardness How improper settings of the simulator can be misleading API dissolution (%) Hardness (N) Pressure 5 kn Pressure 13 kn propeller speed : 5 % propeller speed : 10 % propeller speed : 20 % propeller speed : 30 % propeller speed : 60 % Time (h) Competitive advantage: Quick and easy access to key information QbD initiation at early stage of development Continuous improvement of commercial product Rapid results using minimum amount of powder Number of tablets Skyepharma special features Piezoelectric sensors Press coating module Roller compactor Speakers module Corner

13 Conclusion #1 Time and Cost Efficiency Right First Time Approach

14 1. Patient-oriented, Quality by Design approach 2. Cost reduction and enhanced time-tomarket 14

15 Development and scale up: cost and time reduction By straight to goal development and optimization Screening of raw materials Formulation development Compression cycle of API grades Compression cycle of excipients Pressure/hardness relationship Pressure/hardness relationship Impact of formulation on dissolution Compression cycle RIGHT FIRST TIME Impact of feeding shoe settings Impact of pressure on dissolution Rejection limits determination Impact of tooling characteristics Determination of compression parameters Assessment of critical parameters Setting of scale-up parameters

16 API dissolution (%) Development and scale up: cost and time reduction By anticipating scale up using a compression simulator Comparison of drug delivery on Kilian industrial press and simulator Compression simulator Industrial Press 20 0 Time (h) Example #1: Press coated tablet Delayed release

17 API Dissolution (%) Development and scale up: cost and time reduction By anticipating scale up using a compression simulator Comparison of drug delivery on Hata industrial press and simulator API 1 (industrial) API 2 (industrial) API 1 (simulator) API 2 (simulator) Time (min) Example #2: Trilayer tablet Biphasic release

18 Development and scale up: cost and time reduction By reducing batch size and shortening timelines Step Simulator Batch size* Industrial press Simulator Time* Industrial press Tool assembly h 5 h Setting of comp. parameters 50 g 1 kg 0.5 h 1.5 h Production of trial batch 100 g 33 kg 1 h 2 h Disassembly + cleaning h 20 h SAVINGS % *Skyepharma case study based on a monolayer tablet transfer

19 General Conclusion The Right People The Right Focus Right First Time The Right Technology

20 Come and meet our team! Stand 41A10