Pharmaceutical Technology Transfer

Practices into Design Control Systems

for Combination/Convergent Products
Roy Fennimore
Research Fellow
Product & Process Scientific Solutions (P2S2)
Johnson & Johnson
INTERPHEX New York City, NY 24 April 2013

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“I don’t get it. We design one pill good for 240 maladies
and Marketing tells us there’s a design flaw.”

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The 5th Wave By Rich Tennant
“Oh sure, I’ve used historical data analysis in the past,
but lately it’s been pretty much hysterical data analysis at work.”

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Agenda
Adapting Pharmaceutical Technology Transfer (TT) into a
Design Control System
Integration Strategy
Linking Pharmaceutical Development to the Design Control
System
Technology Transfer Guideline: Key Concepts for Integration
New Product Development Process – Roadmap and Guides
Translation from Pharmaceutical to Design Control
Deliverables
Design Control Waterfall Diagram vs. Pharmaceutical
Deliverables for Integration
Review Report Outlines: Such as Product Development,
Analytical Test Methods and Process Transfer, if time permits
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Overview
A high level view where Technology
Transfer integration aligns with Design
Control (DC) and the New Product
Development (NPD) Process
Review Report Outlines: Such as Product
Development, Analytical Test Methods
and Process Transfer, if time permits

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Purpose
Provide an overview of how
pharmaceutical technology transfer
deliverables and best practices can
be integrated into the Design
Control (DC) System and the New
Product Development Process for
Combination/Convergent Products

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Integrating Pharmaceutical Technology Transfer (TT) into
Design Control (DC) for New Product Development Process

Objective:
The New Design Control System should
be compatible for device development
and device/drug combination/convergent
product development as well as
compliant with QSR/FDA GLP/GMP/ISO
regulations, standards and applicable
international regulations etc.

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 Adapting Pharmaceutical Technology Transfer into
Design Control (DC) for New Product Development Process (NPD)
Leveraging:
Literature search for “Technology Transfer (TT) Processes” and
benchmarking can be used to identify relevant pharmaceutical development
deliverables to include within NPD Process/Design Control System
Many of the general (TT) practices are applicable and can be adapted for
both device and combination products, –e.g., characterization of product and
process / summary reports
Must realize if your company has a different business model and
development process from pharmaceutical companies
Could utilize Design Control terminology as the foundation for DC system
– The development of any type of product is also similar to the Process
Design Excellence or Six Sigma Practices
– Pharmaceutical requirements can be integrated throughout the design
control process
Timing and ownership can be different in terms of Design Transfer
Project Teams of NPD can own the design to sales launch

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Benchmarking – Some Best
Practices & Applications
Product development roadmap and guidelines
Streamlined system with compliant, clear, concise
documents
Program management and team structure
Support/maintenance for the product development
system
Technology transfer requirements and procedures
Integrated drug-device requirements
Integrated Design/Process Excellence, Six Sigma
Practices

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Integration Strategy for Pharmaceutical TT Deliverables
Resources, Organization, Stage Gates, Dashboards, Business Practices
Design Input: Product Description (Profile and Specifications)
and Toxicology (including Toxicology Animal Studies)
Design Output: Product/Process/Packaging Documentation
Design Verification: Analytical, Assays, Stability Studies
including Packaging Stability Testing
Design Validation: Assay Validation, Regulatory Requirements
including filing and approvals, Clinical Trials
Product/Process Validation: Pre-formulation, Formulation
Development, API, Process Development, Scale-up, Process
Validation, Facility Start-up and Validation, Pre-Approval
Inspection Preparation and PAI.
Technology Transfer: Technology Transfer Plan, Updates and
Transfer 10
Example of Pharma Integration Management &
Team Approach
1. Develop communication strategy
Communicate the roles and responsibilities of pharma integration especially in the areas that overlap
Generate a list of pharmaceutical deliverables for integration and reach agreement with the teams
Communicate the timing of deliverables
Regular updates to the management team

2. Identify pharma gaps and leverage best practice pharma deliverables from Literature and
Benchmarking
Identify gaps - VOC, project lessons learn (e.g. On-going Device projects), mapping, internal audits or
external observations
Identify leveragable material from literature – Pharmaceutical/Medical site visits, if possible (process,
deliverables, guidelines, SOPs, etc.)

3. Generate pharma related requirements and provide these requirements to respective teams
Develop a pharmaceutical deliverable integration matrix
Partner with respective teams based on the pharma deliverable integration matrix

4. Coordinate with other teams in company method generation

Provide content expertise
Recommend what needs to be integrated and what could be stand-alone documents
Draft/Review pharmaceutical specific sections for the integrated ones
Draft/Review specific pharmaceutical methods for stand-alone documents if required

5. Coordinate with other teams in the reviewing process

6. Create internal guides

Draft/Review the ones that require the pharma deliverables

7. Provide training after approval of method generation 11

Linking Pharmaceutical Development to
Design Control Pharmaceutical Product Development
can be Viewed as Two Separate but Integrated Processes

Pharmaceutical Product Development

“Claims” Development
Discovery Commercialization
“Process” Development

“Claims” development
– Integrates clinical, regulatory, and marketing strategies
– Optimizes claim structure, product positioning and promotional
messages
“Product/Process” development
– Integrates chemistry, formulation, and manufacturing
– Optimizes product/process specifications, cost and production
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Pharmaceutical Product Development and Device
Development Can Differ in Several Key Areas
• Product development cycle time
– Pharma development can be as long as ten years
– Device development is usually less than three years
• Product design and specification
– Drug products are defined by the results of clinical trials
• Discovery-driven and little can be done to modify the drug substance to meet customer
needs
• Process focuses on maximizing what is discovered to get best label for given indication
• Development more like a legal process as in “claims” made
– Devices are specified to meet market needs
• Products can usually be engineered to a much greater degree
• Process focuses on optimizing commercial potential by focusing on trade-offs between
options
• Development can be heavily customer-driven
• Magnitude of development effort
– Since pharmaceutical drugs take so long to develop and typically require over $500M to bring to
market, a significant number of personnel are involved with a project (as many as several
hundred)
– Device development can be tailored to the size of the project—from minor upgrades to significant
technology implementations; however, their size is usually no where near that of drug
development 13
Technology Transfer Guidelines –
Key Concepts for Integration
Technology Transfer Strategy and General
Checklist

Pharmaceutical Development (PD) Summary

and PD Report after Transfer

Analytical Development (AD) Summary, AD

Report after Transfer

Product/Process Transfer Report

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CDA1
Definitions
Technology Transfer Strategy and General Checklist
The Strategy is a written document that outlines the agreements made between
Development and Operations concerning the technology transfer.
The “Checklist” is a detailed list of development requirements and
corresponding documentation that guide the collection of technology transfer
knowledge for a specific project.
Analytical, Pharmaceutical Development Summaries and Reports
The summaries are a compilation of technical product knowledge, according
to the strategy established, takes place during the NPD phase. The activities
performed during NPD phase are within the R&D environment and in
accordance with Operations expectations. Reports document production
scale development activities that occur after the actual transfer from
Development to Operations has taken place.
Product/Process Transfer Report
Locks in the core product and process information prior to manufacture of the
registration batches and to document comparability between the new product
developed in R&D and the final to-be-marketed product.

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Slide 15

CDA1 May want to consider making this into 3 slides (or have each definition fade in so that you focus the viewer on what you want him/her
to see/read.
CAllman1, 2/10/2009
Technology Transfer (TT) Pharmaceutical Overview
Define & Measure Analyze Design Verify and Validate Monitor

Initiation Starting Product Defined Product Evaluated

Gate Gate Gate Closing

Commercial
Product and Process Filing and
Concept Product and Process Evaluation
Development Launch
Evaluation
Registration Batches
•API Characterization,
•Pre-formulation,
Formulation, Early
Process Dev

•Product
TT Start File PAI
(Sourcing Decision) Transfer
•Pharmaceutical Report
•Route of Administration
Development
•Early Analytical Dev Summary •Pharmaceutical
Development Report
•Early Stability •Analytical
•Analytical
•Technology Transfer Development
Development Report
Strategy and Checklist Summary
Manufacturing
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Operations
Product Development File File

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 Linking Pharmaceutical Product Development to Design Control
(Example of a Roadmap)
Im plem entation Ba se Bu sin e ss
Conc ept Pha se Fea sibility Ph a se Dev elopm ent Pha se Pha se Pha se
Stage 0 Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
Di scover y Efficacy & M FG
Pr oof of Conce pt Pr oduct & Pr ocess De f Dose & Scale Def Lice nsure & Launch Li fe Cycl e M anagement

Design Inp ut - Product Specification

T arget P roduc t P rofile Define P roduc t S pecific ations

Risk Manage ment – Animal Studies

In Vitro Toxicology

G LP Starts
A cute Toxicology Animal S tudies Chronic Toxic ology Animal S tudies .

PA I Preparation
Process Devel opme nt and Valid ation
GM P Star ts Facility S tart-up & Validation PAI Commercial P roduction
P re-Formulation Form ulation Development A ss ay V alidation P roduc tion S upport
API P rocess Development & S cale up De s ign P rocess V alidation
Fr eeze
Design O utput
Produc t/Proc ess/P ac kag ing Doc um ent atio n • Product D ev elopment File (DH F)
• Product Transfer Report
• Pharma ceuti cal D ev elopment Summ ar y • Pharma ceuti cal D ev elopment Report
• Anal yt ic al D ev elopm ent Summa r y • Anal yt ic al Dev elopm ent Report

Design Ve rification – Test Meth ods & Stab ility Studies

A nalytic s Development Develop & Qualify Charac terization & Releas e As says for RM, P roc ess , & P roduc t T rans fer Ass ays
Anal yt ic al D ev elopm ent R eport
Anal yt ic al Dev elopm ent Summa r y

P roduc t S tability S tudies

P ac kaging S tability S tudies S tability Study Updates

Start Final Stability Study Expir ation Date

Design Valid ation (P rod uct) – Safety and Efficacy Es tablis hed
Regulatory Filing P reparation and Submis si on

IND NDA Subm iss ion Re gulator y Approval

Subm iss ion
P has e II
P has e I T rials T rials P has e III T rials P has e IV T rials

FIH Pivotal Tr ial Starts

Design T ransfer/ Design Cha nge
T ec hnology T rans fer TTP TTP
P lan (TT P ) Update T ec hnology T rans fer
Update
Technolog y
Transfer Strateg y

Planning/Review Phase Review Phase Review Phase Review Phas e Review Phase Review Phase Review
• Product Dev . Plan
(Clinical, R egulator y,
• PDP Updates • PDP Updates
• Launch Strateg y
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CM C, etc.)
Generate a Roadmap for New Product
Commercialization Process
• What it is…. • What is it used for…
– Could be a one-page
overview of New Product
Development Process for – Used by project teams
Commercialization as a template for
– Captures steps, timing and repeatable and
sequence, phase disciplined project
deliverables, and roles and planning and
responsibilities management
– Describes timing and – Can serve as a
sequence of Design and reference to
Business Reviews management oversight
– Can be aligned with
Process Design Excellence
/ Six Sigma methodology
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The Roadmap should illustrate a high level
commercialization process, but also serve as a tool for project planning & execution.
Main Themes:
Must be relative to your system today, the most unique aspects of this
process are the phases. The phases should be well defined and can be
staged to promote technical excellence.
For example, the first phase may focus on defining the scope of the project,
gathering user requirements, and translating these into technical
requirements (specifications targets) prior to selecting a concept.
For example, the next phase could be mainly about project planning and
concept selection.
The third phase could be about developing the concept and processes used
to make that concept into a final design.
Business reviews could be separated from the technical design reviews to
promote the Technical Design Reviewers focusing more on the technical
aspects of the program. The Design Reviews and Project Management
Reviews can be scaled for simpler programs.

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Develop Internal Guides for New Product
Development to Commercialization
• What is it… • What are they used
– A guide for each step for…
on the Roadmap, it – Drive consistent and
could describe tasks, repeatable project
inputs, outputs, best- planning and
practices, etc. management
– Linked to Quality – Capture key
System requirements planning
– Linked to applicable assumptions and
Process DEX /Six Company’s best-
Sigma Tools practices
– Serve a primer and
training reference for
the NPD process
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 Design Control Waterfall Diagram vs.
Pharmaceutical Deliverables for Integration
Design Input – Output
User
Technical
Requirements
Requirements Product/Process Development Reports
Analytical Development Design Characterization and Design Summaries
Technical
Summary
Design
Input Pharmaceutical Dev Summary
Final Documentation for Product &
Design Process Process Specifications

Design
Design &
Development Output
Planning
Technology Transfer
Strategy and Checklist
Verification and Validation
Summaries
Design Verification
Design and Development
Planning

Design Validation Medical Product

Validations Including:
Facility Validation
Cleaning Validation Cleaning,
Validations Facility, Analytical
Including: Product/ Process Transfer
Method, Equipment Process Validation Product
Report Transfer Report
Test Method Validation Cleaning, Facility, Analytical Method Pharmaceutical
PharmaceuticalDev
Dev
Report
Report
Analytical
AnalyticalDev
DevReports
Technology Transfer of Knowledge from R+D to Commercial Operations Report
Analytical Method
Transfer
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 Integration of Key Pharmaceutical
Reports/Summaries Concepts
1. Summary of the development history and any changes since development.

2. Documents comparability of the product and process from development to

commercialization. This is accomplished in the summaries by documenting that the
impact of any relevant design changes does not affect the validity of the verification
and validation activities.

3. Documents the critical links between the product and process from pivotal clinical
activities, registration, and finally to commercialization. This can be documented
through an equivalency assessment in the summary or report.

4. Justification and rationale to support the final commercial product and manufacturing
process through an equivalency assessment in the summary or report.

5. Locks the critical product, process and analytical information prior to the manufacture
of initial registration and ISS batches. This can be accomplished through the
successful completion of validation and summarized in the process validation
summary or report.
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 Technology Transfer General Checklist
Detailed List could have 10 more Items per Subject Bullet
Active Pharmaceutical Ingredient General Product Information
(API) Drug Product

• General API Information • Components

• Physical Description • Composition
• Characterization and Proof of • Specification and Test Methods for
Structure Inactive Components
• API Manufacturer • Manufacturer
• Synthesis/Method of Manufacture • Methods of Manufacturing and
• API Process Controls Packaging
• Reference Standard • Specifications and Test Methods
• Specifications and Analytical Test for Drug Product
Methods • Drug Product Container Closure
• API Container Closure System System
• API Stability • Drug Product
Microbiology/Sterility
• Drug Product Stability

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 Pharmaceutical Development
Summary Outline
Executive Summary: Process Flow Diagram with process parameters
• Comprehensive summary focusing on the and acceptable ranges.
development of the drug product and manufacturing • Manufacturing equipment requirements and
process. principle of operation.
Introduction: • In process controls.
Development Strategy: • Cleaning assessment
• Describe of the decision path and supporting rationale Packaging:
and justifications taken in during the development of • Rationale for immediate container selection.
the drug product and manufacturing process. Include • Immediate container
all issues and risks. description/supplier/specification .
Information on the API: Batch overview:
• Chemical Structure and molecular formula. • Development batches trending table to include:
• List special properties relevant for the product and/or • Batch number and size
process development.
• API lot number
• Specifications
• Where and when batch was made
Drug product:
• Purpose of the batch
• Formula rationale for excipients (include sensitivities
such as heat, light, etc.). • Analytical result of the batches
• Formulation history. Critical parameters:
• Specifications/suppliers of excipient. • Discussion of critical parameters identified
from lab and pilot scale.
• Product specifications.
• Process Capability Report/Results
Manufacturing process:
References: References to detailed reports that are
• Manufacturing process rationale. identified in your checklist.
• Manufacturing history

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Analytical Development
Summary Outline

Introduction: Instrumentation:
• General information on the API: chemical • Rationale for critical instrumentation
structure, name and code number. parameters, reagents, utilities and other
Impurities and degradants: relative instrumentation information.
• Rationale for the selection of the specified Control of change:
impurities and degradants (if applicable).
• Description and rationale for method
• Provide historical data from explorative and
full product development. changes.
Analytical methods: Training:
• Rationale for the choice of the analytical • Training requirements and support on all
method for a particular specification and also methods used for the testing of raw
provide in this section: materials, active ingredient(s) and
• Analytical method evaluation (ring test) finished drug product.
and validation Conclusion:
• Analytical Method Development Report • Conclusions resulting from the available
• Robustness testing method development data supporting
• Drug Product stress degradation studies the methods presented in the regulatory
• Analytical Method transfer reports filing.

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Product/Process Transfer Report Outline
Pharmaceutical development summary: Product specifications and test methods:
• Brief description of the drug product • A summary table identifying the test,
development history. specification and corresponding
Scale-up summary: analytical method.
• Brief description of the manufacturing Manufacturing process:
development history from pilot scale to full • Comparison of the manufacturing
scale. equipment, operating parameters and
Product Composition: IPC limits for each step of the process
• Comparison of each separate ingredient in between the development site and the
the product and corresponding quantitative manufacturing site.
composition between the development site • Explanation of any differences
and manufacturing site. encountered between the development
• Explanation of any differences encountered site and manufacturing site.
between the development site and • Process flow diagram
manufacturing site. • Manufacturing instructions
Raw Materials: Packaging:
• Comparison of each separate raw material • Packaging description including
and corresponding code number, supplier, reference to specifications.
trademark and specification reference Validation:
between the development site and • Process and cleaning validation
manufacturing site. strategies and/or reports
• Explanation of any differences • Sterilization validation strategy and/or
encountered between the development site reports (if required)
and manufacturing site. Stability:
Immediate container: • Registration stability strategy and
• Comparison of each immediate container stability protocol.
component, supplier and specification Conclusions:
reference between the development site • Conclusions concerning the scale-up
and manufacturing site and any differences experiences.
encountered. • Development team and Operations team
approval signatures.
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Pharmaceutical Development Report Outline
after Transfer
Manufacturing process:
Purpose/Scope: • Manufacturing process from pilot
Product description: scale to full scale history (including
• Short description about the product and biobatch).
attributes. • Process flow diagram
Executive summary: • Batch overview table with:
• Clinical and commercial formulations Batch number, size and purpose
API lot number, location and date
overview.
of manufacture
• Manufacturing process scale-up overview. • Identify equipment train and
Active pharmaceutical ingredient: equivalency with pilot scale
• Include molecular structure, weight and • List critical parameters with
formula, relevant physico-chemical operating ranges
characteristic and specifications • Provide acceptance criteria and in-
Drug Product: process ranges
• Formulation development history and Cleaning validation:
equivalency between clinical formula and • Description of cleaning validation
commercial formula (if different). • Description of cleaning method and
• Purpose, rational and characteristics for relevant results and criteria.
each excipient with the corresponding Conclusion:
supplier and specification references. • Conclusion on robustness and
• Qualitative and quantitative descriptions control of the final drug product and
for each formulation. manufacturing process including
• Rationale for all product specifications. stability summary and shelf-life
statement. Provide equivalency
with bio-batch and/or pivotal clinical
batch(es).
References: 27
Analytical Development Report
Outline after Transfer
Purpose / Scope:
Product information: Specifications:
• Short description about the • Specifications with the
product. justification.
Executive summary: Stability:
• Submitted methods overview. • Stability summary or report.
• Methods classification with regard Control of change:
to their use for stability and/or • Applied control of change and of
release purposes. the communication with the
• Transfer process status to the QC regulatory bodies overview.
Operations sites with references Conclusion:
to the transfer documents (your • Conclusions resulting from the
checklist). available method development
Method development: and transfer data supporting the
• Selected methods rationale. methods presented in the
• Experience summaries of the regulatory filing.
stability development groups and References:
the QC Operations sites when • Method descriptions, robustness
applying the methods. and validation report references.
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 Key Outputs/Documents for Technology Transfer (TT)
of Knowledge for Combination/Convergent Products
• Process Overview and Process flows - Details of Process
Description and format (Excel or Visio) for process flow
diagrams
• SPC Strategy – Control Points, etc.
• Characterization Strategies/Studies/Reports
• CTQ Flow Down and Basic Process Science/Process
Principles
• Critical Setup Parameters
• Failure Modes; Probable Cause/Solution
• Process - Specific Troubleshooting Guides and Technical
Manuals
• Main Equipment Items and Function Detail
• pFMEA – Risks, Mitigations, Impacts 29
 Key Take-aways from the Technology Transfer Guidelines
• Standardize checklist for transferring product development, process
development and analytical method development knowledge
– Describes the key requirements that must be completed or addressed
throughout the pharmaceutical development process
• Requirements are summarized in key deliverables and reports such as:
– Technology Transfer Strategy, Technology Transfer Checklist,
Pharmaceutical Development Summary, Analytical Development
Summary, Product Transfer Report, Pharmaceutical Development
Report, Analytical Development Report
• In developing a drug-device development model, must identify applicable
requirements and integrate them into the development process
– Product description to be updated to include inputs for active
pharmaceutical agent
– New pharma-specific requirements such as dose, route of administration,
elution kinetics and metabolism of the drug substance

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 Thank you for your participation today
Special Thanks to the following individuals:
• Angela Falzone
• Saurabh Palkar
• Theresa Scheuble
• Diana Dai
• Dave Blazek
• Rich Tennant
If time allows, audience can share some of their best-
practices, experiences and lessons-learned
Don’t forget to complete the evaluation forms !

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