bils 2015 bayer pharma ag markus eser

BioInnovation 2015 (London)

Transfer of Biopharmaceutical Processes

Markus Eser Bayer Pharma AG

Global Biological Development

• Global Biological Development • BioInnovation 2015

Agenda Introduction Challenges Concepts

Introduction


Source: Wikipedia

Introduction


Sources: Wikipedia

Source:worldpress.com

Introduction


Source: Wikipedia

Source: evilmadscientist.com

Introduction


Source: Wikipedia

Biologics


Source: Wikipedia

Process


Cell expansion and fermentation

Depth filtration Capture Polish

Nano- filtration

Ultra- filtration

Bulk storage Purific.

USP DSP

THE PROCESS IS

THE PRODUCT

Process

Process

DS DP

A


Processes within Process

DS DP

A


Processes within Processes

DS • USP • DSP •  (Modifications)

DP • Formulation • Fill & Finish

A •  IPC • Release • Extended


Processes Have Series of Steps

DS • USP • DSP •  (Modification)




DSP •  Capture •  Purification •  Polish •  Nano-Filtration •  Ultra-Filtration •  Bulk

Process Steps have Specifications

DS • USP • DSP •  (Modification)




DSP •  Capture •  Purification •  Polish •  Nano-Filtration •  Ultra-Filtration •  Bulk

Capture •  Resin •  Loading density •  Flow-rate •  Column dimensions •  Buffer composition •  …

One Process - Many Layers


Source: Wikipedia

Product


Source: Wikipedia

QC

Quality Attribute Aggregation

C-terminal lysine

Deamidated isoforms

Galactose content

Afucosylation

Sialic acid content

High mannose content

Non-glycosylated HC

Oxidation

DNA

Methotrexate

HCP

Protein A

ICH Q6B: “ A specification is defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described.“

Process & Product


Cell expansion and fermentation

Depth filtration Capture Polish

Nano- filtration

Ultra- filtration

Bulk storage Purific.

USP DSP

THE PROCESS IS

THE PRODUCT

Process Changes & Product


94

95

96

97

98

99

100

0 2 4 6 8 10 12 14

% M

onom

er

Batch #

HP-SEC

(hypothetical example)

Acceptance Limit

Process change + Changes

QC: •  Release Analytics •  IPC / IPM •  Extended Characterization •  Stability Studies

Impact

Process Changes & Causes


Process Change

Optimization

Process Transfer

Time

Process Changes & Reasons


Changes by

Transfer Scale

Optimization

Facility

Equipment

Know-how

Safety Is Not Negotiable


Safety

Product

Process Changes

Process Changes & Comparability


Process Changes & Effort


Minimal Significant

Extent of process change

Hig

h Lo

w

Com

para

bilit

y Ef

fort

Most preferred

Least preferred

1 2

3 4

•  Easy to assess impact of process change

•  Product resulting from process change similar to original

•  Difficult to analyze and compare product to original

•  Process change results in significantly different product

•  E.g. filtration, manufacturing site or scale-up

•  E.g. cell line, fermentation, downstream protocols

Process Transfer

Site A Transfer Site B


Process Dev. Pilot Plant

Development Manufacturing

In-house CMO

Process Transfer

Site A Transfer Site B


Changes

Process Transfer

Process (site) A Transfer Process

(site) B


Changes

Process Transfer

Product A

Transfer Product A*


Control Strategies

Changes

Phases of Process Transfer

Sourcing Planning Transfer Control Production


Identification & qualification of the right facility

Transfer Master Plan Transfer Teams Timelines

Document Transfer Knowledge management Expert exchange

Change Management Risk Management

Documentation Procurement Readiness Manufacture

Stages of Process Transfer



Planning Timelines


Timelines Production

Transfer

Documentation

Procurement

Regulatory

Planning Transfer Team


Transfer Team

Process Donor (site A)

Process Acceptor (site B)



Transfer Lead

Production

Process Development

QC

Regulatory QA



Transfer Lead

Production

Production manager

Technical

Engineering

Documentation

Process Development

QC

Regulatory QA

Planning Transfer Master Plan

Transfer Master Plan

Timelines •  Production •  Transfer •  etc.

Transfer Team •  Composition •  Responsibilities

Documentation •  Present •  To be

Process Information •  Data, know-how •  Raw materials •  Auxiliary materials

Quality & Regulatory •  Risk Management •  Change

Management


Planning Control Documentation

Transfer

Document Collection

Process Information

Raw & auxiliary materials


Organized Meetings

Transfer

Organized Meetings

Document Collection

Process Information

Document Tracking

Common Data

Access



Enablers

Essentials

Transfer

Organized Meetings

Document Collection

Process Information

Process knowledge

Document Tracking

Common Data

Access



Transfer Process Information & Process Knowledge

Process Information

•  Raw materials & auxiliary materials •  Test methods

•  Cleaning procedures

•  Facility Requirements •  Environmental Requirements •  Training Requirements •  IPC

•  Specifications & test methods

•  Product specifications •  Test methods

•  Acceptance criteria

•  Packaging •  Specifications & test methods

Process Knowledge

•  Development reports •  Risk analysis & design space

•  CPP

•  CQA, CMA & Acceptance ranges

•  Process description •  BPRs / MBR

•  Equipment Requirements

•  Manufacturing history •  Validation protocols & reports •  Stability

•  Shelf life

•  Storage requirements

•  Shipping conditions •  Stability reports

•  Holding times


QbD

Control


Process site A Transfer Process

site B

Changes

Control

Organized Meetings

Document Collection

Process Information

Process knowledge

Document Tracking

Common Data

Access



Control Gap Analysis & Risk Management

Organized Meetings

Document Collection

Process Information

Process knowledge

Document Tracking

Common Data

Access



Gap

-Ana

lysi

s R

isk

Man

agem

ent


Process Site A Step 1 Step 2 Step 3 …

Process Site B Step 1 Step 2 Step 3 …

FMEA

Step 2

…


Gaps

Step 2

…



Ris

k C

omm

unic

atio

n Risk Identification

Risk Analysis

Risk Evaluation

Result / Output of Quality Risk Management Process

Ris

k R

evie

w

Review Events

Ris

k C

ontro

l

Risk Reduction

Risk Acceptance

Ris

k A

sses

smen

t

unacceptable

ICH Q9



Risk Assessment

Process Comparison(Gap Analysis)

Evaluation of change

FMEA

YES

Risk classification

scoring

Evaluation by process risk assessment

No

Change acceptable

Change not aceptableChange acceptable

with further risk mitigation

Risk Assessment Output

Patient view:

ProductSafety & Efficacy

Process knowledge

Change ProcessMitigation Strategy

Ris

k A

sses

smen

t R

isk

Con

trol

Tran

sfer

Safety Is Not Negotiable


Safety

Product

Process Changes

Tools : •  Planning •  Transfer Process •  Risk Management •  Comparability

Forward-Looking Statements This presentation may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management.

Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com.

The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.


Thank you!


bils 2015 bayer pharma ag markus eser

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