TECH TRANSFER AND QRM TIM HOWARD, PE CPIP VICE PRESIDENT - - PowerPoint PPT Presentation

▶
tech transfer and qrm
SMART_READER_LITE
LIVE PREVIEW

TECH TRANSFER AND QRM TIM HOWARD, PE CPIP VICE PRESIDENT - - PowerPoint PPT Presentation

Oct 07, 2023 465 likes •1.13k views

TECH TRANSFER AND QRM TIM HOWARD, PE CPIP VICE PRESIDENT COMMISSIONING AGENTS, INC SAAPI Conference Bytes Conference Centre, Midrand Friday, Oct 6 th , 2017 COMMISSIONING AGENTS, INC. 460+ 9 150 $500M+ 21 Years Agents Business Active

slide-1
SLIDE 1

TECH TRANSFER AND QRM

TIM HOWARD, PE CPIP VICE PRESIDENT– COMMISSIONING AGENTS, INC

SAAPI Conference Bytes Conference Centre, Midrand Friday, Oct 6th, 2017

slide-2
SLIDE 2

COMMISSIONING AGENTS, INC.

460+ Agents

Global Presence

$500M+

Services delivered

9 Business Areas 21 Years

Of safety excellence

A global partner in providing professional services to enhance operational performance and reliability.

LOCAL SERVICES

Asset Management & Reliability Automation & Information Technology BioVokeTM eVLM Building Commissioning Commissioning & Qualification Full Scale OperationsTM Human Performance Owner’s Project Management Quality, Compliance, & Regulatory Process & Manufacturing Technologies

Pacific Noth West 12 Pacific 26 Mountain 33 Mid West 43 INDIANAPOLIS AND/OR REMOTE Administration 5 Operations 18 DataVoke 28 New England 50 Mid-Atlantic 30 South Atlantic 50 South East 30 Puerto Rico 23 Northern Europe 42 Italy 10 China 38 Singapore 23

GLOBAL IMPACT

When you need to meet a higher standard.

150 Active Projects

slide-3
SLIDE 3

Connecting Pharmaceutical Knowledge ispe.org

What is Technical Transfer?

ISPE The systematic approach that is followed in order to pass the documented knowledge and experience gained during development and/or commercialization to an appropriate, responsible, and authorized party ICH Q10 Transfer of product and process knowledge between development and manufacturing, and within or between manufacturing sites to achieve product realization

new product transfers during development through manufacturing transfers within or between manufacturing and testing sites for marketed products

slide-4
SLIDE 4

Connecting Pharmaceutical Knowledge ispe.org

Key References

ICH Q8R2 ICHQ10 ISPE Tech Transfer Guide 2014 ISPE PQLI guides WHO guide 2011 EMEA annex 15 Draft annex 12- lifecycle management

slide-5
SLIDE 5

Connecting Pharmaceutical Knowledge ispe.org

Technical Transfer Examples

New product to the market

Limit client risk yet maximize speed to market

Scale-up of an existing process

Creative solutions typically required for implementation

Movement of production to new facility

New can cost less. Like for like expected.

Process improvements

Continual improvement to improve product cost a must

slide-6
SLIDE 6

Connecting Pharmaceutical Knowledge ispe.org

Types of Technical Transfers: Risk Assessment

Each type of Tech Transfer comprises similar risk elements The risk assessment needs to include key cross-functional activities that comprise the boundaries of a TT

Sending Receiving New Product Same or Single Market New or Multiple Market(s) Existing Production Line New Production Line Equivalent Equipment Equipment Change >10x Scaleup Process Change New Process Site 1 Site 1 No Low Med NA Med Low Med/High High Med/High High Site 1 Site 1 Yes High High Low/Med Med Low High High NA High Site 1 Site 2 No Low Med Low Med Low Med/High High Med/High High Site 1 Site 2 Yes High High Med Med Low High High NA High

slide-7
SLIDE 7

Connecting Pharmaceutical Knowledge ispe.org

Measures of Success of a TT program

Does the approach promote the delivery of working equipment and automation, to achieve smooth transition to full scale operation? Is the approach efficient in terms of effort (cost) and time (schedule)? Is the program product/process focused, initiated with Process robustness ? Will the approach be found acceptable by regulators?

slide-8
SLIDE 8

Connecting Pharmaceutical Knowledge ispe.org

The WHAT – Define Project Scope

Define the Project Scope and establish clear objectives with specific acceptance criteria.

> Proposed Registration and Launch Timings > Safety Information (MSDS, Fire & Health Hazards etc.) > Commercial needs (e.g. forecast Volume) > Cost of Goods > Tech transfer budget

slide-9
SLIDE 9

Connecting Pharmaceutical Knowledge ispe.org

The WHO – Establish the Team

Appoint a Team Leader and Form a cross functional project team

CORE EXPERTISE: Process Development, Manufacturing Operations - (manufacturing, engineering and maintenance, production QA, QC, Validation) SUPPORT EXPERTISE: Regulatory affairs, EHS, Medical, Marketing, Supply Chain

slide-10
SLIDE 10

Connecting Pharmaceutical Knowledge ispe.org

The HOW – Establish the Plan

Develop a Comprehensive Execution Plan that captures:

> Goals and timing > Facility fit and regulatory strategy > Process tech transfer requirements > Managing documentation > Effective Team Communications > Roles and Responsibilities > Project schedule and resource requirements & tracking team performance

slide-11
SLIDE 11

Connecting Pharmaceutical Knowledge ispe.org

Documentation Hierarchy

TT Master plan Subplans TT Risk Assessment Process Robustness study TT SOP/protocols/Templates/reports

slide-12
SLIDE 12

Connecting Pharmaceutical Knowledge ispe.org

  • Program Management Plan
  • Technology Transfer Plan
  • TT Project Execution Plan
  • Lifecycle Phase Checklist
  • Subordinate plans/Reports
  • CQV
  • Cleaning
  • Materials Mgt/Control
  • Supply Chain
  • Analytical Methods Validation
  • PQS
  • PM tools
  • Schedule/Action/Decision logs

CAI Tool Box

slide-13
SLIDE 13

Connecting Pharmaceutical Knowledge ispe.org

Technology Transfer Master plan

slide-14
SLIDE 14

Connecting Pharmaceutical Knowledge ispe.org

TT Checklist

Dev = Development, Mfg = Manufacturing, Eng = Engineering, Reg = Regulatory, QA = Quality Assurance, Anl = Analytical, Val = Validation, Legal = Legal, PM = Project Management, Log = Logistics, EH&S = Environmental, Health, and Safety, Dis = Function E-E = Existing Drug to Existing site, E-N = Existing Drug to New Facility, N-E = New Drug to Existing Facility, N-N = New Drug to New Facility.

Type PROJ Activity Phase Dis Deliverable Ref Project

E-E Technical Development Initial Process Description Initial Product Description Dosage and Delivery Materials (consider European/Japanese/United States Pharmacopoeia or Multi-compendia) Specifications Method Development Instrumentation Needs Process / Product Development Reports Development History Report Manufacturing Monograph Prior to Transfer or Feasibility Dev, Mfg, Eng, Reg, QA Go/No-Go Decision E-N N-E N-N E-E Write Confidential Disclosure Agreement (CDA) Approve CDA Feasibility QA, Legal Approved CDA E-N N-E N-N E-E Evaluate Facility and Utilities Evaluate Equipment Evaluate Process Capability Evaluate Technical Capacity Evaluate Analytical Capabilities Evaluate Regulatory Implications Evaluate Material Logistics Feasibility Dev, Mfg, Eng, Reg Anl Feasibility Assessment Report E-N N-E N-N E-E Assess Quality Systems Assess Prior Regulatory Inspections Feasibility QA/Val Audit Report

slide-15
SLIDE 15

QUALITY PROCESS STAFF FACILITY PROJECT

SPECIFICATION & DESIGN COMMISSIONING & QUALIFCATION ASSET PERFORMANCE PROCUREMENT & CONSTRUCTION QUALITY SYSTEM PROJECT DELIVERY SYSTEM ROLE SPECIFICATION & DEVELOPMENT ROLE ASSIGNMENT ROLE QUALIFICATION TECHNOLOGY TRANSFER PROCESS CONTROL STRATEGY STARTUP LOGISTICS CONTINUOUS PROCESS VERIFICATION COMMERCIAL LOGISTICS PROCESS PERFORMANCE QUALIFICATION ACCEPTANCE AND RELEASE

Our Solution. The Chemistry of Full Scale Operations (FSO)TM

slide-16
SLIDE 16

QUALITY PROCESS STAFF FACILITY PROJECT

Tech Transfer Plan Process Knowledge Transfer Process Risk Management Control Strategy Process Validation Plan Startup Logistics Supporting Validations Process Performance Qualification Staff Qualification Plan Role Specification Role Assignment Role Qualification Organizational Learning Facility & Equipment Plan Facility & Equipment Specification Continuous Improvement Project Plan Commissioning & Qualification Plan Qualification Tech Transfer Phase Design Phase Construction Phase Operations & Maintenance Phase Verification Phase Acceptance & Release Maintenance & Calibration Operational Procedures Change Management Issue Management Turnover Document Management Pharma- covigilance Basis of Design Detailed Design Process Performance Qualification Vendor Management Construction Quality Assurance Quality Manual Quality Risk Management Design Review Commissioning Detailed Design Feasibility/ Concept Study Audit Management Equipment Risk Analysis Marketing Authorizations Supplier Management Commercial Logistics Continuous Process Verification

Our Solution, in Detail. The Chemistry of Full Scale Operations (FSO)TM

slide-17
SLIDE 17

Connecting Pharmaceutical Knowledge ispe.org

Summary

  • TT subset of Product Realization
  • Knowledge Transfer is a key element to all TTs
  • Upfront work to define complexities, resource needs, and understand

business/regulatory strategy allows for smoother and more successful TT

  • Risk management enables a more streamlined lifecycle effort
  • Solid understanding of company’s quality management system essential

to defining requirements and flexibility that will be allowed

slide-18
SLIDE 18

QUALITY RISK MANAGEMENT

slide-19
SLIDE 19

Connecting Pharmaceutical Knowledge ispe.org

References

ICH Q9 “Quality Risk Management” FDA Guidance on Process Validation ICH Q8 (R2) “Pharmaceutical Development” ASTM E2500 IEC 60812

Analysis techniques for system reliability – Procedure for failure mode and effects analysis (FMEA)

19

slide-20
SLIDE 20

Connecting Pharmaceutical Knowledge ispe.org

Risk Management is Universal across all Industries

Common Elements

What can go wrong? How often does it happen? How bad are the consequences? Is the risk acceptable?

Key Differences

Risk criteria Technology involved Nature of the hazard Whether the system is static or dynamic

slide-21
SLIDE 21

Connecting Pharmaceutical Knowledge ispe.org

Risk Management In the Drug Industry

ICH Q9: Quality Risk Management

Drug Company Strategic Risks Operational Risks Financial Risks Quality Risks Competitor Advantage Company Viability Shareholder Harm Patient Harm EHS Risks Workforce/ Environmental Harm

slide-22
SLIDE 22

Connecting Pharmaceutical Knowledge ispe.org

Quality Risk Management ICH Q9

slide-23
SLIDE 23

Connecting Pharmaceutical Knowledge ispe.org

ICH Q9: Primary Principle #1

“Evaluation of the risk to quality should be based on scientific knowledge (of the product, process and clinical effects) and ultimately link to the protection of the patient” “The level of effort, formality, and documentation of the quality risk management process should be commensurate with the level of risk”

ICH Q9: Primary Principle #2

slide-24
SLIDE 24

Connecting Pharmaceutical Knowledge ispe.org

Risk Assessment

Risk Assessments HAZOP FEMA FMECA FTA HAACP PHA Risk Ranking Statistics

slide-25
SLIDE 25

Connecting Pharmaceutical Knowledge ispe.org

Risk Management Tools

Tools HAZOP FEMA FMECA FTA HAACP PHA Risk Ranking Statistics

slide-26
SLIDE 26

Connecting Pharmaceutical Knowledge ispe.org

Risk Assessment

slide-27
SLIDE 27

RISK ASSESSMENTS

27

slide-28
SLIDE 28

Connecting Pharmaceutical Knowledge ispe.org

QRM Tool Selection

Murray, K. and Reich, S. “Quality Risk Management (QRM) Tool Selection: Getting it Right First Time.” Pharmaceutical Engineering, July/August 2011, Vol. 31 No. 4.

slide-29
SLIDE 29

Connecting Pharmaceutical Knowledge ispe.org

Risk Assessment Options

Failure Modes Effect Analysis

(FMEA / FMECA)

Fault Tree Analysis HACCP Boston Matrix Ishikawa Diagram (Fishbone)

slide-30
SLIDE 30

Connecting Pharmaceutical Knowledge ispe.org

FMEA / FMECA

Assesses failure modes and looks to reduce impact or occurrence of failure Relies on robust process understanding Yields quantitative assessment of risks a risk priority number (RPN) Methodical in nature, can be time consuming

slide-31
SLIDE 31

Connecting Pharmaceutical Knowledge ispe.org

FMEA / FMECA

Typically applied to an equipment or system boundary Level of effort may not be justified

Use as deep dive for high risk items

slide-32
SLIDE 32

Connecting Pharmaceutical Knowledge ispe.org

Process FMEA Example

List Process Steps Assess Severity of Risks to Patient Assess Probability

  • f

Occurrence Assess Probability

  • f Detection

Identify Hazards to Patient

List the severity of each hazard listed in previous step. The severity rating is independent of design features or detection mechanisms. With an understanding of the design features and other risk control mechanisms, assess the probability of

  • ccurrence

With an understanding of the detection mechanisms and design features, assess the probability of detection

Critical Aspects = Those design features and functions that serve to reduce probability of

  • ccurrence or enhance

probability of detection

slide-33
SLIDE 33

Connecting Pharmaceutical Knowledge ispe.org

Scoring Options

Use a 3 to 5 point scale (Quantitative)

1, 3, 5 1, 5, 10 1, 4, 7 10 1,10, 100

Qualitative

Low, Med ,High Negligible, Low, Med, High, Unacceptable

RPN Limits or Thresholds

Risk is Acceptable or Unacceptable Grey Zone Suggested

slide-34
SLIDE 34

Connecting Pharmaceutical Knowledge ispe.org

Aseptic Filling Line - Isolator

Isolator Sanitized with VHP Product Transfer Line cleaned with CIP and sterilized with SIP Filling Head parts cleaned in Washer and sterilized in Autoclave Tubing Replaced each lot

slide-35
SLIDE 35

Connecting Pharmaceutical Knowledge ispe.org

Process Steps

Prepare Equipment Load Vials Wash Vials Depyrogenate Vials Fill Vials Weigh Vials Stopper Vials Convey Vials

slide-36
SLIDE 36

Connecting Pharmaceutical Knowledge ispe.org

Hazards to Patient

Wash Vials

Dirty Vials not adequately Washed resulting in contaminated dose Contamination from Water or Air ???

Depyrogenation

Vials do not reach time at temperature resulting in endotoxin dose contamination Contamination from Air???

slide-37
SLIDE 37

Connecting Pharmaceutical Knowledge ispe.org

Example Output

Process Step Hazard Severity Controls Probability Detectibility RPN Wash Vials Dirty Vial not Washed Depyro Vials Endotoxin Contamination (Time at temp not reached) Depyro Vials Microbial Contamination from Air

slide-38
SLIDE 38

Connecting Pharmaceutical Knowledge ispe.org

Example Output (Quantitative)

slide-39
SLIDE 39

Connecting Pharmaceutical Knowledge ispe.org

Critical Aspects

Belt Speed Control, Indication, Alarm Tunnel Temperature Control, Indication, Alarm Airflow Velocity, Loss of Airflow Alarm Acceptance Criteria driven by process requirements

slide-40
SLIDE 40

Connecting Pharmaceutical Knowledge ispe.org

Fault Tree Analysis

Assumes a failure has occurred with a process or product Evaluates sub-process steps and causal effects Represented pictorially as a logic diagram May be good for root cause analysis or for assessing impact of multiple factors

slide-41
SLIDE 41

Connecting Pharmaceutical Knowledge ispe.org

Fault Tree Analysis

Graphical methodology that examines combinations of possible events with undesirable results Human and System Failures Good for integrated systems analysis, forcing us to think across system boundaries Intended for assessing designs and processes for risk

slide-42
SLIDE 42

Connecting Pharmaceutical Knowledge ispe.org

Fault Tree Analysis

Start by picking the worst event results and work down to possible causes Technique inherently encourages prioritization of events Uses a set of symbols to depict actions and relationships

= “AND”: combination of events triggers fault = “OR”: one of several possibilities triggers fault

slide-43
SLIDE 43

Connecting Pharmaceutical Knowledge ispe.org

Standard FTA: Common Example

Car Collision at Intersection Adverse Event AND Side Road Car Fail to Stop Main Road Traffic Present Speeding On Phone Distracted Driver Kids Noise OR Late Drinking

slide-44
SLIDE 44

Connecting Pharmaceutical Knowledge ispe.org

Hazard Analysis and Critical Control Points (HACCP)

Structured approach applying technical and scientific principles Analyze, evaluate, prevent, and control the risk or adverse consequence(s) of hazard(s) Considers design, development, production, and use of products

slide-45
SLIDE 45

Connecting Pharmaceutical Knowledge ispe.org

Hazard Analysis and Critical Control Points (HACCP)

Looks for physical, chemical, and biological hazards to process Requires sufficient process understanding to identify critical control points Focus is on lifecycle of product, not just manufacturing process

slide-46
SLIDE 46

Connecting Pharmaceutical Knowledge ispe.org

From 21 CFR 123.6

List the hazards that are reasonably likely to occur List the critical control points for hazards List the limits for each CCP List the procedures, and frequency for monitoring CCP List corrective action plans for deviations from CCP limits List the verification procedures Provide for a recordkeeping system that documents the monitoring of the CCPs

slide-47
SLIDE 47

Connecting Pharmaceutical Knowledge ispe.org

Boston Matrix

80 / 20 Rule Drive focus to area of most need Drive focus to actions with most impact Drives discussion Documents decisions

slide-48
SLIDE 48

Connecting Pharmaceutical Knowledge ispe.org

Response to Design Review

slide-49
SLIDE 49

Connecting Pharmaceutical Knowledge ispe.org

FAT Planning

slide-50
SLIDE 50

Connecting Pharmaceutical Knowledge ispe.org

Cause and Effect Diagram

AKA: Fishbone or Ishikawa diagram Widely used for Root Cause Analysis Used to examine:

Man, Method, Machinery, Materials

Effective when output coupled with another tool

slide-51
SLIDE 51

Connecting Pharmaceutical Knowledge ispe.org

Sample Formulation Process

Formulation Tank CIP/SIP Buffer Prepared Bulk Drug Substance Thawed Buffer and Formulation Added to Formulation Vessel Mixed and Sampled Transferred to Filling Area

slide-52
SLIDE 52

Connecting Pharmaceutical Knowledge ispe.org

Formulation Process

WFI / CIP / SIP WFI / CIP / SIP

Sterilizing Filter To Intermediate Vessel in Filling Area

M

FORMULATION VESSEL Thawed Bulk Drug Substance Sterile Transfer Vent Filter Transfer

Manual Addition Of Buffer Kit

Buffer Prep Vessel

M

Pump

slide-53
SLIDE 53

Connecting Pharmaceutical Knowledge ispe.org

Hazards to Process

Microbial Contamination Protein Degrades or Denatures Cross Product Contamination Wrong Formulation Endotoxin Contamination Foreign Material Contamination

slide-54
SLIDE 54

Connecting Pharmaceutical Knowledge ispe.org

Cause and Effect Diagram

slide-55
SLIDE 55

Connecting Pharmaceutical Knowledge ispe.org

Cause and Effect Diagram

slide-56
SLIDE 56

Connecting Pharmaceutical Knowledge ispe.org

Cause and Effect Diagram

slide-57
SLIDE 57

Connecting Pharmaceutical Knowledge ispe.org

Cause and Effect Diagram

slide-58
SLIDE 58

Connecting Pharmaceutical Knowledge ispe.org

Cause and Effect Diagram

slide-59
SLIDE 59

Connecting Pharmaceutical Knowledge ispe.org

Cause and Effect Diagram

Cause of Cause

slide-60
SLIDE 60

Connecting Pharmaceutical Knowledge ispe.org

Work Shop

slide-61
SLIDE 61

Connecting Pharmaceutical Knowledge ispe.org

Cause and Effect

Analyze one of the previously identified hazards

Microbial Contamination Protein Degrades or Denatures Cross Product Contamination Wrong Formulation Endotoxin Contamination Foreign Material Contamination

Identify at least three 1st Tier Causes Identify at least six 2nd Tier Causes

slide-62
SLIDE 62

Connecting Pharmaceutical Knowledge ispe.org

Microbial Contamination Protein Degrades or Denatures Cross Product Contamination Endotoxin Contamination Foreign Material Contamination

WFI / CIP / SIP WFI / CIP / SIP

Sterilizing Filter To Intermediate Vessel in Filling Area

M

FORMULATION VESSEL Thawed Bulk Drug Substance Sterile Transfer Vent Filter Transfer

Manual Addition Of Buffer Kit

Buffer Prep Vessel

M

Pump

slide-63
SLIDE 63

Connecting Pharmaceutical Knowledge ispe.org

Cause and Effect Diagram

slide-64
SLIDE 64

Connecting Pharmaceutical Knowledge ispe.org

Thank You!

Timothy P. Howard, CPIP, PE Vice President Commissioning Agents, Inc.