PowerPoint Presentation Six-Sigma... · • In this presentation we will use how lean six sigma techniques [D efine M easure A ... Review what is CTQ and ensure these measure points

BASAS 2018

A Six-Sigma Approach in defining Programming Strategy of recurring deliverables

JAGAN ACHI ASSOCIATE DIRECTOR, JAZZ PHARMACEUTICALS

Agenda

• Lean and Six Sigma concepts • Application of Lean Six Sigma to Drug Development recurring deliverable [DSUR]

Introduction

• Development of strategy for programming recurring deliverables/tasks is very common in drug development process.

• Statistical Programming groups in various companies use different techniques and methods to develop processes which would help there teams to achieve desirable outcomes.

• Selecting a right approach requires a careful planning and thorough understanding of the requirements and measuring, analyzing how the chosen approach is working and finally training the staff to implement it.

• In this presentation we will use how lean six sigma techniques [Define Measure Analyse Improve Control] can be used to define the right strategy with an example for generating Development Safety Update Reports [DSUR].

Lean • An improvement methodology based on customer centric definition of value and

providing that value in the most effective way possible, through a combination of the elimination of waste and a motivated and engaged workforce. Focus is on elimination of waste.

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Over-production

Inventory Transportation

Over Processing

Waiting

Motion

Defects

Six Sigma Focus is on the quality improvement through reduction of variance

Define

• What is the Problem?

• What is the Scope?

• What key metric is important?

• Who are the stakeholders?

Measure

• What data is available?

• Is the data accurate?

• How should we stratify the data?

Analyze

• What are root cause of the problems?

• Have the root causes verifies?

• Where should we focus our efforts?

• What clues have been uncovered?

Improve

• Do we have the right solutions?

• How will we verify the solutions work?

• Have the solutions piloted?

• Have we reduced variation?

Control

• What do we recommend?

• Is there support for our suggestions?

• What is our plan to implement?

• Are results sustainable?

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SIPOC Understanding the Process

• Provides the “before” picture so that you can compare “after” picture, hopefully demonstrating improvement Suppliers, Inputs, Process Steps, Outputs, Customers [SIPOC]

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Supplier Input Process Output Customer

Define

CTQ – Critical to Quality

• Translate the broad requirements to specific, measurable and actionable performance requirements

• Start with the need and establish the quality requirements

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Need Quality Requirement

Performance Requirement

Measure

Process Analysis

• Identify 7 wastes of Lean • Approach to problem solving by identifying which of your process steps are value

added and which are non value added

• TIMWOOD

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Measure

Effort & Impact Analysis

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Improve

Return on Investment

• Evaluate the efficiency of instrument • Compare the efficiency of a number of different investments • 1. Map the future state process. Review what is CTQ and ensure these measure

points are in your future state • 2. Identify the measurable improvements compared to the current state • 3. Calculate ROI

• Benefit- from future state • Current cost is from current state • Make all assumptions and calculations clear

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Improve

Control Plan

• Sustain the gains identified from the project • Ensure Standardization of the future process such that the product always meet

customer requirements

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Control

DSUR

• Development Safety Update Report [DSUR] is an annual report provided to the regulatory agencies

• Purpose is to regular Safety assessment of subjects in investigational drug to assess the benefit/risk before approval.

• Timing of DSUR is dependent on the sponsors first authorization to conduct a clinical trial in any country worldwide. Date of authorization will determine the annual reporting period.

Challenges

• Multiple regulatory agencies [FDA, EMEA] require different reports • Multiple times output generation • Cross functional coordination with PVG, Statistics, Programming and Data

Management • Multiple developmental phases for the drug • Vendor management to coordinate the data extract, SDTM transfers or ADaM

transfers

Define - Requirements

• ICH Guidelines: • http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/

09/WC500097061.pdf

• Biostatistics and Programming Requirements: • Outputs: Summary Reports and not datasets for Submission

• Datasets: Adverse Events, Demographics, Disposition, Exposure, Deaths • Data Mapping to standard controlled terminology • Programming of Summary tables and Listings • Derivation Rules:

• Treatment Emergent AE • Data Lock Dates • Exposure calculation, Subject Years • Maintaining Blinding

Shells

Shells

Shells

Shells

Approaches and Process analysis

DB SDTM ADaM DSUR

Output

DB SDTM + ADaM

DB ADaM+

DSUR Output

DSUR Output

Multiple

Define

Approaches and Process analysis

DB SDTM ADaM DSUR

Output Multiple

Measure

Approaches and Process analysis

DB SDTM + ADaM DSUR Output

Measure

Approaches and Process analysis

DB ADaM+ DSUR Output

Measure

Approaches and Process analysis

DB SDTM ADaM DSUR

Output

DB SDTM + ADaM

DB ADaM+

DSUR Output

DSUR Output

Multiple

Analyze

Effort & Impact Analysis

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Improve

DB SDTM ADaM DSUR

Output

DB SDTM + ADaM

DB ADaM+

DSUR Output

DSUR Output

Multiple

Control Plan

Identify the best approach based on the principles and document a as Standard Operating Procedures or Work Process Documents. Train the team members on the new process and manage the change within the organization.

Summary and Discussion

• Lean six sigma principles can be applied to any process improvement • Applying the methodological technique would eliminate the seven types of wastes

and would help in gaining efficiencies within any organization

‘Its not the strongest that survive, nor he most intelligent, but one most responsive to change’ Charles Darwin