PAT - Seen from an Automation and Information Solutions Provider

Transcription

1 PAT - Seen from an Automation and Information Solutions Provider Alberto Rossi Rockwell Automation 09. October 2007 Copyright 2007 Rockwell Automation, Inc. All rights reserved. 1

2 Agenda Rockwell Automation At-a-Glance Industry Drivers PAT Strategies Case studies Summary 2

3 Overview - Focused on Life Sciences Over $1.0B installed base in Life Sciences Active industry leadership: PDA, JETT, ISPE, ISA88, ISA95, ISA99, MESA, WBF Installed at 95% of the Fortune 50 pharmaceutical companies 75% of top 150 Life Sciences OEMs Strengths in Plant Floor Control and Information Management offer RA solutions 3

4 Agenda Rockwell Automation At-a-Glance Industry Drivers PAT Strategies Case studies Summary 4

5 Industry Acceptance: Major Milestones Industry Acceptance FDA Introducti on User consortium established to drive PAT standard 50% of leaders initiate PAT programs Pfizer - $10M 250 programs FDA is involved in 12 Projects and there are 30 Letters of Intent Today Embedded methodology for all new projects Initial Results of Pilot Prg. PAT Standard Defined Full Scale Program Implementati on The FDA would like PAT to become commonplace not to be an initiative. John E. Simmons PhD US Food and Drug Administration 5

6 Manufacturing Excellence PAT Discrepant Product High quality, with high scrap & rework Old Paradigm: Increase product testing to improve product quality Result: Better product quality, but higher scrap and product rework rates, extend production time. New Paradigm: Increase process quality to improve product quality. Result: Better product quality and lower scrap and product rework rates, reduce production time. Process Quality Source: IBM BCS 2005 End Product Quality The PAT Paradigm Shift 6

7 Manufacturing Excellence - FDA s View Best practices in quality management methods, particularly in other high-tech industries, have undergone significant progress since 1978 when the CGMP regulations were last updated. The FDA wants to ensure its regulatory practices encourage similar progress... -FDA 7

8 Agenda Rockwell Automation At-a-Glance Industry Drivers PAT Strategies Case studies Summary 8

9 Pharmaceutical CGMPs for the 21st Century: Encourage the early adoption of new technological advances by industry Facilitate industry application of modern quality management techniques, to all aspects of pharmaceutical production and quality assurance. Ensure that regulatory review, compliance, and inspection policies are based on state-of-the-art pharmaceutical science Enhance the consistency and coordination of FDA's business processes and regulatory policies concerning review and inspection activities Adopt a model that benefits FDA, the industry and the consumer Pharmaceutical CGMPS for the 21 st Century A Risk Based Approach Final Report

10 PAT Strategies Risk-Based Approach Control of Risk Critical Process Parameters Failure Analysis & Mgmt Assessing Patient Risk Risk of Non- Compliance Technology Transfer Process Understanding Scientific Understanding Causes of Variability Control of CPP s Predict Quality Attributes Regulatory Strategies Validation, Change Control, Equipment Qualification Real-Time Quality Assurance End Product Quality Real-Time Release In-Process Data Final Product Data Lab Data Material Attributes Lagged Quality By Inspection Real-Time Quality By Design 10

11 Paradigm Shift from Conventional to PAT Example: Oral Solid Dosage Manufacturing ventional Approach Lab-centric, offline testing of product quality End-of-phase quality testing reduces risk moving to next stage Quality by Inspection Raw Materials Dispensing Granulation Mixing / Compression / Milling Blending Drying / Coating Packaging Hold & Release 11

12 PAT Process Monitoring & Control Example: Oral Solid Dosage Manufacturing Measure Critical Parameter s Correct Process PAT Approach Online & at-line monitoring & control of CPP s Continuously test quality during phase eliminates risk moving to next stage Raw Materials Dispensing Granulation / Milling Mixing / Blending Drying Compression / Coating Packaging Quality by Design Real-Time Quality Assurance NIR Material Identification Power Consumption Granulation End Point On-line blend uniformity End Point Control Vision Particle Analyzer NIR Conformance Testing Acoustic Granulation End Point On-line vision particle size analysis NIR Core Potency NIR Coating Thickness Imaging of Blisters 12

13 Batch recording today Materials preparation Weighing, Preparing Dispensing, Mixing Instructions and verifications Equipment PLCs, Scada, DCs. Recipes, instructions, calibration schedules PM schedules, cleaning schedules, alarm lists, PV trend plots Manual operations, sampling, laboratory testing BMs, CMMs LIMs Operator instructions, activity verifications, recorded values, deviations, signatures Utilities reports, alarm lists, historion reports trends,... Utilities & environmental systems ( ie; WFI, air quality ) Paper Batch Record 13

14 ...Right First Time Manufacturing with EBR On-Line preparation instructions, verification, and materials reconciliation Equipment Operators Environment (e.g. sterile rooms) W&D Part11 EWI Warehouse PCS BMS Complete Electronic BATCH Record Electronic MASTER BATCH Record PAT PAT PAT LIMS Real Time Automation and Information Control and Decision Management LIMS Part11 Real time release 14

15 RA s vision for Electronic Batch Recording Potenti al Saving s EBR real time release EBR parametric release EBR review by exception EBR manual review Paper based systems Ticket system Paper on glass EBR High integration PAT - EBR Manufacturi ng Capability 15

16 Agenda Rockwell Automation At-a-Glance Industry Drivers PAT Strategies Case studies Summary 16

17 Case Study 1: PAT in a Solid Dosage Manufacturing Process Case Study #1 Process Raw Materials Dispensing and sieving Granulation and milling Mixing / Blending (actives & excipients) Drying Compression / coating Packaging Instrumentation NIR Mid-IR Raman UV-Vision Fluorescence Vision particle characterization Focused Beam Reflectance Measurement (FBRM) Particle Vision Microscopy Acoustic spectroscopy 17

18 API 1630nm Avicel 1425nm Lactose 1450nm Raw Chemicals: Raw Materials HE H7 Process Knowledge Mapping Through Multivariate Analysis H2 HB 8 x 63 = 504 kg Approx. 8 x 25 = 200 kg 8 x 31 = 248 kg Water/LOD BLENDING Case Study #1 0 testing~chem quality(e.g. ph,roi,ipt ) 1 usage~weight 2 power~time 3 energy to reach 55 C at exhaust 4 LOD 5 granulation yield data 6 blending yield data not numbered hold time Glidant deg C "wc deg C deg F deg F Lubricant /10/02 2:02:45 PM Min(s) 11/10/02 2:48:55 PM Water Water vessel Lot Number Air exhaust C FBD Supply Air Temperature FBD Supply Air Flow FBD Exhaust Air Temperatur FBD Supply Air Humidity - FBD Pre-Chill Air Temperat FBD DH Regen Temperature GRANULATION Standard deviation Resource (vessel) Id 2 8x % power Vibratory Separator Asset number Blend sample number 1 30Kg 1 10Kg 8x 36 kg 4 ø< 1mm ø> 1mm Impact Mill + 40 kg SIFTING 120 kg 156 kg 120 kg Granulator Fluidized Bed Dryer 3 Air 95 C High Flow = scfm Process Flow = scfm 960 kg DISPENSING, PRE-MIX GRANULATION DRYING 5 min (+0.5) min Max 4x (3+10+5s ) min SIFTING & SIZING 5 Hold Time < 1 month 1000 kg BLENDING 10±5 min 6 18

19 Data Mining Problem Data available from multiple sources/formats Electronic (time series, EBR, LIMS, spreadsheets, ) Paper (charts, reports) Expert knowledge Need: convert data into information For management For operators For automatic control Use data mining results to Design control improvements Real time decision making Case Study #1 19

20 Case Study - Goals Case Study #1 Apply the Feature selection Automatically rank all 140 parameters Use top three parameters to create an empirical model Achieve 0.9 or better correlation with filtered quality data Achieve 0.7 or better correlation with raw quality data Able to predict quality property to within 1 standard deviation Copyright 2005 Rockwell measurement Automation, Inc. All rights reserved. accuracy 20

21 Case Study - Results Case Study #1 Q-actual (blue) Q-predicted (red) Time Blue: standard deviation (measurement) Red: model prediction error Q-predicted Feature Selection - Empirical Model Time Q-actual 1-std Top three parameters used in the model One process parameter One environmental parameter One raw material parameter Model results available during initial stages of production Model result = additional valid measurement 0.9 or better correlation with filtered quality data 0.7 or better correlation with raw quality data 21

22 Summary of Case Study Results Case Study #1 Model prediction is feasible for this batch process Impressive modeling accuracy Determined list of ranked critical process parameters with respect to two key quality properties Next step: use the model (or the knowledge) during real time operation to reduce process variation 22

23 Case Study : RA Demonstration (Solution based on Industry Standards) Rockwell Automation has significantly complemented our point of view and added key manufacturing elements to our sciencebased approach for reducing revenue@risk, said Doug Dean, senior executive, Global Quality and Value-Driven Compliance, IBM Healthcare and Life Sciences. The Proof-of-Concept is the first demonstration of how complex solutions can be integrated with a compliance-centric architecture to transform a pharmaceutical organization s development and manufacturing processes. 23

24 Proof of Concept: IBM s Proof of Concept (PoC) Business goals Science (PAT) & Risk based approach in NPD, manufacturing, and supply chain mgmt. Preferred Technologies & Technology Asset Alignment Industrialization Processes & Collaboration Feedback loops from MFG to NPD Demonstrate end-to end business process management deployment Technology goals Demonstrate Technology Integration (Enterprise Application Integration, Web Services, plug n play Vendor SW, ) Platform to integrate unit and enable enterprise PAT Coexistence of Websphere & Netweaver Demonstrate key principles of Business Process Management, including process specification, process activation in runtime, process enforcement & compliance, Closed loop process management Demonstrate key principles of integrated security management 24

25 Agenda Rockwell Automation At-a-Glance Industry Drivers PAT Strategies Case studies Summary 25

26 Solutions for Manufacturing Competitiveness R&D Clinical Producti on From R&D thru Clinical to Commercial Manufacturing Knowledge Experience 26

27 Solutions for Manufacturing Competitiveness ERP Informatio n Strategy From R&D thru Clinical to Commercial Manufacturing Connect plant floor to business system Information Tactics Automatio n Data 27

28 Solutions for Manufacturing Competitiveness Continiou s Batch Discrete From R&D thru Clinical to Commercial Manufacturing Connect plant floor to business system API Intermediate Product One single platform for multiple disciplines 28

29 Solutions for Manufacturing Competitiveness Distributed From R&D thru Clinical to Commercial Manufacturing Centralized Connect plant floor to business system Standalone Unit Area Plant/Enterpri se One single platform for multiple disciplines Scalable from OEM to Enterprise solutions Standardize KPIs across the enterprise 29

30 Solutions for Manufacturing Competitiveness Level 4 Level 3 Level 2 Level 1 Business Logistic Plant production Scheduling, Shipping, Receiving, Inventory, etc.. Manufacturing Operations Management Dispatching, Detailed Production Scheduling, Production Tracking,... Continio us Control Batch Control Discre te Contro l From R&D thru Clinical to Commercial Manufacturing Connect plant floor to business system One single platform for multiple disciplines Scalable from OEM to Enterprise solutions Standardize KPIs across the enterprise Based on S88/S95 Level 0 30

31 PAT Solution Space Map Services Project Services Training Life-Cycle Network Asset Mgmt Compliance & Quality Partnerships IBM E+H Encompass Partners Others 31

32 Alberto Rossi Sr Consultant Copyright 2007 Rockwell Automation, Inc. All rights reserved. 32