PDA: A Global and Manufacturing Association David Tainsh, GSK - - PowerPoint PPT Presentation

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PDA: A Global and Manufacturing Association David Tainsh, GSK - - PowerPoint PPT Presentation

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Innovation in Medicines PDA: A Global and Manufacturing Association David Tainsh, GSK Keith Pugh, MHRA Joint Regulators/Industry QbD Workshop 28-29 January 2014 London, UK Introduction Current State We have heard a lot about the

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SLIDE 1

PDA: A Global Association

Innovation in Medicines and Manufacturing

David Tainsh, GSK Keith Pugh, MHRA

Joint Regulators/Industry QbD Workshop 28-29 January 2014 London, UK

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SLIDE 2

Introduction

  • Current State

– We have heard a lot about the challenges and successes of applying QbD – Aside from Biopharms which we know are complex, Immediate Release Products are just the tip of the iceberg and we need to be more innovative if we are to be successful in delivering consistent and reliable quality for all products.

  • Future State

– So before we close this workshop we just wanted to reflect on some of the new challenges facing us, what could be different and to ask how do you see it?

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SLIDE 3

Challenges to Innovation

  • Current Levels of Technical Capability
  • Availability of New Skillsets
  • Unwillingness to Deploy New Technology
  • Large Investment in the Current State
  • Perceptions of High Regulatory Hurdles
  • Lack of Process to Manage Complex LCM

Changes

  • Lack of an Overall Vision on How to Modernise

Pharmaceutical Manufacture

3

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SLIDE 4

Opportunities for Innovation

  • Novel Product Types for QbD

– More Complex Traditional Medicines

  • Prolonged release Oral, Inhaled DPI, Nanoparticulates

– Novel products

  • Advanced Therapeutics, Oligonucleotides, Microneedles
  • Novel Methods of Manufacture & Control

– Continuous – Synthetic Biochemistry - Biotransformations – Discrete Manufacture & Novel Analytics

  • Others?

4

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SLIDE 5

Continuous Manufacturing:

  • Enabling Things Batch Can’t Do

Process Factory Business

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SLIDE 6

Enzyme Chemoenzymatic Approach Enzyme

Cascade Synthesis

Synthetic Biochemistry

Moving to Microbial Cell Factories

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SLIDE 7

Liquid Dispensing Technology Platform

Industrial scale machine installed to provide Phase 3 and Launch Capability Capacity: 1 million tablets/day, upgradable to 2 million/day

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SLIDE 8

Manufacturing - A Paradigm Shift

“Population of Many”

Quality assessed by sampling post manufacture

Mfg….. Batch Mfg….. Discrete Units

Quality assessed on-line for every tablet

“Population of One”

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SLIDE 9

Drug Solution or Suspension + Placebo Tablets Low Volume (c. 2-20ul) Dispensing On-Line Analysis Chemical Imaging Surface Coating & Printing

Liquid Dispensing Technology with PAT

Drying

IR or Microwave

  • 1. Image analysis
  • 2. NIR Chemical

Imaging

  • 1. Vision system,

droplet size

  • 2. Droplet weight

UV / NIR [suspension concentration] No Linkage between First and Last Tablet

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SLIDE 10

Video Image of Droplet: “What was Delivered”

Process Analytical Technologies

NIR Chemical Imaging: “Where on the Tablet”

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SLIDE 11

80 82 84 86 88 90 92 94 96 98 100102104 10 6 108110112114116 11 8 LSL

  • 3.*S

N

  • minal

+3.*S U SL 25 50 75 100 125 150

Comparison of Droplet Content Uniformity vs Typical 2mg Tablet Content Uniformity

6.94E6 6.96E6 6.98E6 7E6 7.02E6 7.04E6 7.06E6 7.08E6 7.1E6 7.12E6 7.14E6 7.16E6 7.18E6 7.2E6 7.22E6 7.24E6 7.26E6 7.28E6 7.3E6 7.32E6 7.34E6 7.36E6

LSL

  • 3.s

+3.s USL 50 100 150 200 250 300 350

Frequency

Droplet N= 606 PpK =16 Tablet N= 520 PpK =1.4 115% 85%

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SLIDE 12

Control and Testing

Incoming core tablet Dosing Drying Coating & Printing 100% Vision QC Inspection System monitoring – tablet shift register and rejection confirmation UV Solution Analysis Reticule Calibration Drop Volume/Dose Content Wet Dose Position Inspection Droplet Weight Check Pad Inspection/ Coating Confirmation Tunnel Temp. Conditions NIR Dose Position Inspection 100% Vision QC Inspection

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SLIDE 13

Desired State

  • A Vision to Modernise Pharmaceutical

Manufacture

  • Enabling Regulatory Strategy and Process that

keeps pace with Innovation

  • Increased Opportunities for Scientific Dialogue

around innovative platforms

  • Education and Training to Provide New Skillsets
  • Enhanced scientific and risk based approaches

to QbD to match new technologies

  • A Simplified and Streamlined Variations Process

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SLIDE 14

Challenges to Innovation

  • Current Levels of Technical Capability
  • Availability of New Skillsets
  • Unwillingness to Deploy New Technology
  • Large Investment in the Current State
  • Perceptions of High Regulatory Hurdles
  • Lack of Process to Manage Complex LCM

Changes

  • Lack of an Overall Vision on How to Modernise

Pharmaceutical Manufacture

14

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SLIDE 15

Desired State

  • A Vision to Modernise Pharmaceutical

Manufacture

  • Industry driven
  • Enabling Regulatory Strategy and Process that

keeps pace with Innovation

– Facilitate within existing Regulation

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SLIDE 16

Desired State

  • Increased Opportunities for Scientific Dialogue

around innovative platforms

  • Scientific Advice (EMA/NCA)
  • Working Parties e.g. QWP, BWP
  • PAT team
  • early interactions recommended
  • Education and Training to Provide New Skillsets
  • Should also include Regulators

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SLIDE 17

Desired State

  • Enhanced scientific and risk based approaches

to QbD to match new technologies

  • Apply and build on existing learning
  • A Simplified and Streamlined Variations Process
  • EU legislation (Common system since August 2013)
  • Changes already classified on a risk based basis
  • Detailed classification guideline

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SLIDE 18

Type IA Type II

Evaluation Procedure adapted to the level of risk

Changes not requiring any prior approval Changes requiring prior approval

Type IB (Default) Extension

Design Space Variations

Summary - Types of Variations

‘Do & tell’ ‘Tell, wait & do’

No submission required if within an approved design space

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SLIDE 19

Desired State

  • A Simplified and Streamlined Variations Process
  • EU - Changes already classified on a risk based basis
  • Additional flexibility – Post Approval Change

Management Protocol (PACMP)

  • justify downgrading in type of required variation
  • no restrictions to the nature of changes
  • limit (Type IB) regarding level of downgrading for

biopharmaceutical products.

  • Global challenges
  • What do you want?

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SLIDE 20

Conclusion

  • By No Means a Comprehensive View of

the Challenges Facing All of Us or the Possible Solutions

  • But a Stimulus for Further Discussion
  • So How do you See the future Challenges

and Opportunities for Innovation?

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