ABB Industries PAT Validation

Transcription

1 Alison Harrington ABB Industries PAT Validation ABB Industries - 1 -

2 Topics PAT disciplines and framework FDA evolution PAT Regulatory Process Quality System Comparability Protocol Submission example Validation approach Technology Partnership Streamlined Validation ABB Industries - 2

3 Process Analytical Technology: PAT is a system for designing, analyzing, and controlling manufacture 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. Mathematical Chemical Risk analysis Integrated Disciplines Physical Validation Microbiological ABB Industries - 3 Build in Quality by Design

4 PAT Framework Design and develop processes that can consistently ensure a predefined quality at the end of the manufacturing process Introduce quality by design and whilst improving efficiency Gains in quality, safety and/or efficiency will vary depending on the product and are likely to come from: Reducing production cycle times by using on-, in-, and/or at-line measurements and controls Preventing rejects, scrap, and re-processing Real time release Increasing automation to improve operator safety and reduce human error Facilitating continuous processing to improve efficiency and manage variability Using small-scale equipment (to eliminate certain scale-up issues) and dedicated manufacturing facilities Improving energy and material use and increasing capacity. ABB Industries - 4

5 Process Analytical Technology tools Multivariate data acquisition and analysis Process analyzers Process and endpoint monitoring and control Continuous improvement and knowledge management ABB Industries - 5

6 Changing Environment Manufacturing and associated regulatory practices (do) did not adequately support or facilitate innovation and continuous improvement An innovative regulatory process was necessary to transform pharmaceutical manufacturing to meet current and future needs ABB Industries - 6

7 FDA PAT Regulatory Milestones FDA Advisory Committee for Pharmaceutical Science 19-July-2001 FDA PAT Subcommittee Meetings February, July, October 2002 Draft PAT Guidance September 2003 Final PAT Guidance September 2004 PAT Team Certification completed September 2004 ABB Industries - 7

8 FDA PAT Guidance Incorporates flexible Regulatory Strategy accommodating innovation by PAT Team approach to Review and Inspection Jointly trained and certified staff ABB Industries - 8

9 FDA PAT Regulatory Process Review and Inspection PAT System Implementation Options Regulatory Process Team Approach: Review and Inspection PAT Submission Information PAT Comparability Protocol ABB Industries - 9

10 FDA PAT System Implementation Options Under the facility s own Quality System Inspections by the PAT Team or PAT certified Investigator can precede or follow PAT implementation Supplement Submission (PAS, CBE-0, CBE-30, AR, etc.) prior to implementation If necessary, an inspection can be performed by a PAT Team or PAT certified Investigator prior to implemenation Comparability protocol (CP) Submission Outlining PAT research, Validation and implementation strategies and time lines ABB Industries - 10

11 PAT Implementation : Under firm s Quality System Organisation with robust QS may be able to reduce supplement submission Procedures designed to ensure that the drug products have identity strength, quality and purity Concept of Product Lifecycle Identification and control of critical variables FDA Draft Guidance Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations September 2004 ABB Industries - 11

12 Modern Quality System ABB Industries - 12

13 PAT Submission Information : Example Process description Analytical properties Testing and rationale Risk assessment PAT system and sampling description Type of measurement technology (e.g. NIR, spectral region), sampling system (e.g., fibres, if any, sample location, sample/product interface), sampling plan Risk management, including identification of system failure and strategy for managing system failure Experimental design protocol, including table of experiments with justification, and references to documents (experimental design and conclusions) ABB Industries - 13

14 PAT Submission Information : Example Factors identified as critical, factors chosen as critical and chosen for control justification, References to experimental design Modelling strategy and criteria for management of outliers Change control strategy for model maintenance Performance verification, calibration Process monitoring and control strategy Acceptance criteria ABB Industries - 14

15 Critical Parameters and Process Controls Identification Focus on process understanding What parameters are critical to product quality? Experimental Design How are these parameters controlled throughout the process? Feed-back/ - forward ABB Industries - 15

16 Process Understanding and Control of identified critical parameters Assure the quality of in-process materials and/or drug products Continuously validate the performance of the manufacturing process Allow the process to manage variability Assure product quality in real time or near real time ABB Industries - 16

17 PAT Regulatory Risk-Management Expect an inverse relationship between the level of process understanding and the risk of producing a poor quality product Well understood process leads to less restrictive regulatory approaches to manage change Focus on process understanding and the facilities quality system can facilitate risk-managed regulatory decisions and innovation ABB Industries - 17

18 Regulatory Tools by FDA and ICH PAT Guidance, PAT Team, ASTM Standards and support infrastructure Compliance Policy Guide 7132c.08 Draft Guidance on Comparability Protocol Draft Guidance on Quality Systems Approach to Pharmaceutical cgmp Regulations Sept 2004 ICH Q8, Q9 and proposed Q10 will expand the international scope ABB Industries - 18

19 Team Approach : Comparability Protocol A well-defined, detailed written plan for assessing the effect of specific postapproval chemistry, manufacturing, and controls (CMC) changes on the identity, strength, quality, purity and potency of a specific drug product A plan for anticipated future CMC changes CP can be submitted in an original application or a prior approval supplement (post approval) CP concept first introduced for biotechnology products (1997) A well-planned protocol provides sufficient information for FDA to determine whether the potential for an adverse effect on the product can be adequately evaluated and can lower the risk for implementing the change with FDA s prior approval ABB Industries - 19

20 Team Approach : Comparability Protocol ABB Industries - 20 Augments the Scale-up and Postapproval Changes (SUPAC) and Changes to an Approved NDA or ANDA guidance Consistent and complimentary to FDA initiatives on pharmaceutical cgmp for the 21 st century Promote continual process and product improvement and innovation by facilitating CMC changes Could allow an applicant to implement CMC changes and place product in distribution sooner than without the use of a comparability protocol Guidance available at:

21 A Comparability Protocol for Changes in Analytical Procedures ABB Industries - 21 Indicates whether the protocol is being used to modify or change Proposed changes improve or do not significantly change characteristics used in methods validation that are relevant to the type of analytical procedure (e.g. accuracy, precision, specificity, detection limit, quantitation limit, linearity range Plan for validation of the changed analytical procedure, including; Suitability of the analytical procedure Pre-specified acceptance criteria for validation parameters Susceptibility to matrix effects by process buffers/media, product-related contaminants, or other components present in the dosage form Statistical analyses to determine comparability of two procedures When used for release or process control, use of a new revised analytical procedure should not result in deletion of a test or relaxation of acceptance criteria that are described in the approved application.

22 PAT Comparability Protocol : Example ABB Industries - 22 Existing approved and marketed high volume DP Tablet Focus on monitoring and controlling the entire Manufacturing Process: Drug Product and API Jan 2003 project kick-off Nov 2003 to July 2004 several drafts of CP submitted to FDA Aug 2004 FDA pre-operative site visit Oct 2004 PAT CP Submission (deployment stage systems operational on an industrial scale)

23 Tablet manufacture traditional analytical methods ABB Industries - 23 Fixed process conditions Limited confirmation of quality during processing Limited sample sizes

24 Tablet Manufacturing through PAT ABB Industries - 24 With real-time analysis Rapid information Useful for process control Potential to adjust the process to achieve target quality and reduce variation Replace costly, time consuming off-line, laboratory based testing

25 Factors to consider Open, frank and science based dialogue building trust and mutual understanding, throughout the project Commitment to share knowledge as learned Team approach ABB Industries - 25

26 Phased Validation Approach Process and PAT optioneering Early process R&D Technology transfer and scale-up New process registration Base instrument qualification Building blocks Building blocks Building blocks Building blocks Validation strategy development Building blocks Full PAT system validation Phased Validation Approach Building blocks Building blocks Building blocks ABB Industries - 26

27 Associated core competencies The technology is only part of the story! ABB Industries - 27 Plant and process improvement Technical project management Feasibility studies / technology risk management Analytical chemistry / experimental design HAZOP / CHAZOP System build, Integration / testing / commissioning Organisational change management Training Process control strategies Chemometrics and Multivariate statistical analysis competence Regulatory and validation PAT validation strategy Regulatory liaison Data and information / knowledge management ABB Analytics Division -Advanced measurement and transduction Process analytical solutions NIR / FTIR Technology / interfacing Sampling (Sterile / toxic / hazardous) Application development System support / development System improvement / development

28 Client Value ABB PAT Technology Partnership - phases Corporate Vision PAT Program Design Corporate PAT Implementation Program Technology Selection PAT project design Regulatory Liaison Change Management Program Client Client Client / ABB Client / ABB Client / ABB ABB / Client ABB Industries - 28 Appoint Steering Committee Define PAT strategy and vision Set objectives Define key milestones Approve investment program Appoint technology champions Recruit necessary knowledge and competencies where necessary Devise PAT role in R&D Devise PAT role in Tech transfer and Scale-up Devise PAT role in manufacturing license application Prepare time to market scenarios Develop corporate high level requirements specification Evaluate vendor technologies The technology is new choose a vendor willing to invest and jointly develop and improve systems Consider ability to support global implementations and support Consider wider knowledge transfer and technology support capabilities Develop agreement Set up global and local organisations and facilities Establish core processes Establish procedural frameworks and controls Agree roles, responsibilities and skills / competency map Define quality procedures and controls Define risk assessment and management framework (peer review) Produce program Meet with regulators / share vision and objectives Communicate the following via a comparability protocol: - Quality procedures - Scientific integrity measures - Internal audit and peer review processes - Analytical / experimental design - Competence frameworks and competence asessments - Proposed formal reporting and review framework Develop communications and targeted training program Define measure and report KPI s for the technology introduction program Define develop and deliver training programs Value and reward key contributions and behaviors Evaluate and report successes / breakthroughs Form focused improvement teams

29 Client Value Experimental Design / Piloting ABB PAT Technology Partnership - phases Information Management Corporate PAT Implementation Program Stage 1 Validation Stage 2 Validation Ongoing support and maintenance Drive for continuous improvement Client / ABB Client / ABB ABB/Client Client / ABB ABB / Client ABB/Client ABB Industries - 29 Mathematical modeling design and ongoing optimisation Sample system design Analytical method design Analytical method validation -Accuracy - Precision - Repeatability - Robustness -Process coverage Calibration model maintenance and change control Ongoing verification Data and metadata management Devise data and knowledge safety, integrity and archiving systems / procedures Devise data sorting and management systems Devise data mining systems and competence Develop core skills and systems to derive the process models and quality models from data assessment Use findings to influence future experiments Validation of the PAT system as delivered ABB Streamlined Documentation covering: User requirements specification System specification Design reviews System Engineering FAT / SAT IQ OQ Summary reporting Start up training Core use and technical SOP s Validation and QA of the ongoing use of the PAT system Regulatory liaison Performance Qualification Experimental design and review Start-up training Design verification Analytical method validation Statistical model verification and maintenance Periodic review Auditing and peer review frameworks Change control and configuration management Documentation generation and management New projects Technical innovation Project collaboration Completed/ ongoing projects Maintenance Strategy development Reliability centered engineering and maintenance program implementation. Fast response support agreements Collaborative technology / system development support Ongoing validation support Review technology performance Operate key client user / interest group forum Maintain focus on key industry needs / drivers e.g.: - Regulatory - Applications - Advanced control - Biotechnology Continue to invest and become the N o 1 PAT systems partner of choice

30 What is ABB s streamlined documentation option ABB s streamlined documentation suite has been designed to offer our clients within regulated industry the opportunity to start a project with a complete document framework in place. The document framework covers: Design Engineering Testing Quality control Validation ABB Industries - 30

31 Streamlined Documentation Template ABB s Streamlined Documentation process ensures: GAMP4 compliance Compliance with Customer SOP Document uniformity Key Value Proposition: Workload reduction Anticipation: Templates allow customer and ABB to anticipate next steps ABB Industries - 31 ABB CoE Eng. Std. & Manuals Standard Modules and Libraries LS Solution Template Streamlined Documentation

32 Streamlined Documentation Database ABB Industries - 32 ABB CoE Eng. Std. & Manuals Standard Modules and Libraries LS Solution Template Streamlined Documentation

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