Watch the presentation of this webinar here: https://bit.ly/3wT5Irt The Emprove® Program is constantly expanding and updating. Find out about the recently launched Emprove® CCM category for our cell culture media portfolio, the new Emprove® API Information Packages, and the latest updates on available TUPPs for our Emprove® Chemicals portfolio. This virtual user group will introduce the two latest additions to the Emprove® Program: 1. Our latest category Emprove® CCM for our cell culture media with wave 1 focus on our Cellvento® CHO cell culture media portfolio, looking also into the content of our three Emprove® Dossiers. 2. The new Emprove® API Information Packages that are currently created for our Emprove® APIs, looking into the content and showing how to access. Additionally, we'll give an overview of latest Technically Unavoidable Particle Profiles (TUPPs) for our Emprove® Chemicals. In this virtual user group, you will learn: • Emprove® CCM and its documentation for our cell culture media • Content and availability of the new Emprove® API Information Package • Update on available TUPPs for our Emprove® Chemicals

1. The life science business of Merck KGaA,
Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
Emprove® Virtual
User Group
Meeting
Torsten Schadendorf
June 1st 2021

2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada

3. Agenda
1
2
3
The Emprove® Program - an Overview
Emprove® CCM
Emprove® API Information Package
4 Technically Unavoidable Particle
Profiles (TUPPs) - An Update

4. The Emprove® Program –
an Overview

5. ... Convenient
Access ...
... for a Broad
Portfolio.
... to reliable
information ...
The Emprove® Program
at a glance…
Emprove® Virtual User Group Meeting | June 1st 2021
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6. Chemicals Expanding content
PharmaGradeTM Integration in progress
Filters & Single use Constant portfolio expansion, supporting launches
Chromatography Launched Q2/2020
Cell Culture Media Launched Q4/2020
Emprove® Material Qualification Dossier
Emprove® Quality Management Dossier
Emprove® Operational Excellence Dossier
Portfolio, Dossiers, Suite
Emprove® Program
Emprove® Suite
Emprove® Virtual User Group Meeting | June 1st 2021
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7. POLL QUESTION 1
Title of Presentation | DD.MM.YYYY
7
Do the information in the Emprove® Dossiers and/or the Emprove® Suite
help you to assess the risk associated with (please check all that apply)?
o Raw Material Sourcing
o Raw Material Qualification
o Raw Material Performance
o All of the Above

8. Emprove® CCM

9. Product Scope
Emprove® CCM
In scope
 Chemically-defined media
 Selected media for Gene Editing
and Novel Modalities
 Custom Media
Product Family
Cellvento® media (wave 1)
EX-CELL® Advanced Media (wave 2)
EX-CELL® Insect Media (wave 2)
EX-CELL® Lenti Media (wave 2)
Custom Media (wave 3)
Emprove® Virtual User Group Meeting | June 1st 2021
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Out of scope
Standard / classical media (eg. DMEM, GMEM)

10. Dossier Structure
Emprove® CCM
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Operational Excellence Dossier
 Trace Element Information
 Origin of Raw Materials
 Analytical procedures
Supports process optimization
Material Qualification Dossier
 General information
 Specification
 Manufacture
 Address, Manufacturing Flowchart,
ISO Cert, GMP Statement
 Homogeneity Statement
 Characterization Statements
 TSE/BSE, Virus Safety, GMO,
Components of Interest
 Control of CCM
 CoAs, Label, Batch Numbering
 Container closure system
 Stability
Information to start a material
qualification
Quality Management Dossier
 Supply Chain Information
 Product Quality Self Assessment
 Site Quality Self Assessment
 Supplier Management
 Stability data
Answers questions during risk
assessment

11. Dossier Structure
Emprove® CCM
Emprove® Virtual User Group Meeting | June 1st 2021
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Operational Excellence Dossier
 Trace Element Information
 Origin of Raw Materials
 Analytical procedures
Supports process optimization
Material Qualification Dossier
 General information
 Specification
 Manufacture
 Address, Manufacturing Flowchart,
ISO Cert, GMP Statement
 Homogeneity Statement
 Characterization Statements
 TSE/BSE, Virus Safety, GMO,
Components of Interest
 Control of CCM
 CoAs, Label, Batch Numbering
 Container closure system
 Stability
Information to start a material
qualification
Quality Management Dossier
 Supply Chain Information
 Product Quality Self Assessment
 Site Quality Self Assessment
 Supplier Management
 Stability data
Answers questions during risk
assessment

12. Material Qualification Dossier
Emprove® CCM
Emprove® Virtual User Group Meeting | June 1st 2021
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 Specification
 Originial Manufacturer
 ISO 9001 Certificate

13. Material Qualification Dossier
Emprove® CCM
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 Specification
 Originial Manufacturer
 ISO 9001 Certificate
 Manufacturing Process
 Validation Report - Open Part
 Packaging Material
 CoA (examples)
 Product label / batch
numbering system (example)

14. Material Qualification Dossier
Emprove® CCM
Emprove® Virtual User Group Meeting | June 1st 2021
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 Specification
 Originial Manufacturer
 ISO 9001 Certificate
 Manufacturing Process
 Validation Report - Open Part
 Packaging Material
 CoA (examples)
 Product label / batch numbering
system (example)
 Certificates
 TSE/BSE
 Viral Safety
 GMO
 Homogeneity
 Components of Interest

15. Emprove® CCM
Material Qualification Dossier
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16. Quality Management
Emprove® CCM
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 IPEC-PQG GMP Guide applied to Cellvento®
media platform with scope of Emprove® Program

17. Dossier Structure
Emprove® CCM
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Operational Excellence Dossier
 Trace Element Information
 Origin of Raw Materials
 Analytical procedures
Supports process optimization
Material Qualification Dossier
 General information
 Specification
 Manufacture
 Address, Manufacturing Flowchart,
ISO Cert, GMP Statement
 Homogeneity Statement
 Characterization Statements
 TSE/BSE, Virus Safety, GMO,
Components of Interest
 Control of CCM
 CoAs, Label, Batch Numbering
 Container closure system
 Stability
Information to start a material
qualification
Quality Management Dossier
 Supply Chain Information
 Product Quality Self Assessment
 Site Quality Self Assessment
 Supplier Management
 Stability data
Answers questions during risk
assessment

18. Quality Management Dossier
Emprove® CCM
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19. Dossier Structure
Emprove® CCM
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Operational Excellence Dossier
 Trace Element Information
 Origin of Raw Materials
 Analytical procedures
Supports process optimization
Material Qualification Dossier
 General information
 Specification
 Manufacture
 Address, Manufacturing Flowchart,
ISO Cert, GMP Statement
 Homogeneity Statement
 Characterization Statements
 TSE/BSE, Virus Safety, GMO,
Components of Interest
 Control of CCM
 CoAs, Label, Batch Numbering
 Container closure system
 Stability
Information to start a material
qualification
Quality Management Dossier
 Supply Chain Information
 Product Quality Self Assessment
 Site Quality Self Assessment
 Supplier Management
 Stability data
Answers questions during risk
assessment

20. Operational Excellence Dossier
Emprove® CCM
Emprove® Virtual User Group Meeting | June 1st 2021
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21. POLL QUESTION 2
Title of Presentation | DD.MM.YYYY
21
Please rank the following cell culture media information given in the
Emprove® dossiers regarding the value for you (1 = highest value)
o CCM stability data
o Levels of trace elements
o Origin of media components/ingredients
Is ranking within poll questions possible? If not, please use this question: “Which
of the following information shown before are of most value to you?”

22. Emprove® CCM
Dossier Availability (wave 1: Cellvento® media platform)
Emprove® Virtual User Group Meeting | June 1st 2021
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Article Code Product
Emprove® Material
Qualification Dossier
Emprove® Quality
Management Dossier
Emprove® Operational
Excellence Dossier
103840 Cellvento® 4CHO-X COMP Expansion √ √ √
103796 Cellvento® 4Feed COMP New New New
103795 Cellvento® 4CHO New New New
101885 Cellvento® CHO-200 New New New
101883 Cellvento® Feed-200 New New New
102577 Cellvento® CHO-220 New New New
102578 Cellvento® Feed-220 New New New
102485 Cellvento® CHO-210 New New New
102488 Cellvento® Feed-210 New New New

23. Versioning
Emprove® CCM
Emprove® Virtual User Group Meeting | June 1st 2021
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24. Emprove® API Information
Package

25. Emprove® Virtual User Group Meeting | June 1st 2021
25
Emprove® Essential
 GMP (IPEC)
 Moderate risk applications
Emprove® Expert
 GMP (IPEC)
 Higher risk applications
Emprove® API
 GMP (ICH Q7)
Chemicals Categories
Emprove® Evolve
 Non-GMP, manufactured utilizing
GMP concepts and elements
 Evolving regulatory needs
Emprove® Program for Chemicals

26. Content
Emprove® API Information Package
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 General Information
 Manufacture
 Manufacturer
 Certificate of GMP Compliance
 Description of Manufacturing Process
 Specification
 Other relevant product certificates
 Product Quality Self Assessment
 Packaging Information
 Stability Summary and Conclusion
Purpose: Supporting material qualification, not for registration purposes

27. Certificate of GMP Compliance (latest version available on EudraGMDP webpage*)
Emprove® API Information Package
Emprove® Virtual User Group Meeting | June 1st 2021
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* http://eudragmdp.ema.europa.eu/inspections/gmpc/searchGMPCompliance.do;jsessionid=FdxKinNcvHto_mTjMJAtz3O1xm1iK0yrk07LmD-rcl4bCSJrozh6!814916889

28. Other relevant product certificates Package
Emprove® API Information Package
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 TSE/BSE
 Allergen
 Mycotoxin/Aflatoxin
 GMO
 Nitrosamine
 Melamine
 Kosher
 Halal

29. Stability Summary and Conclusion
Emprove® API Information Package
Emprove® Virtual User Group Meeting | June 1st 2021
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30. POLL QUESTION 3
Title of Presentation | DD.MM.YYYY
30
Do you use APIs only for the intended use as API or (potentially) also in
other / adjacent applications (e.g. as excipients in critical formulations)?
o Only as API
o APIs and further/other applications

31. Versioning
Emprove® API Information Package
Emprove® Virtual User Group Meeting | June 1st 2021
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32. Article Product Name Dossier Availability
108432 Urea cryst. EMPROVE®
API Ph Eur, BP, USP √
100164 Boric acid cryst., EMPROVE®
API Ph Eur, BP, NF √
105040 Potassium iodide EMPROVE®
API Ph Eur, BP, JP, USP √
109828 di-Potassium hydrogen phosphate anhydrous, low in sodium EMPROVE®
API Ph Eur, BP, USP √
106235 Sodium acetate trihydrate EMPROVE®
API Ph Eur, BP, JP, USP, FCC, E262 New
106666 tri-Sodium citrate dihydrate low in endotoxins, EMPROVE®
API Ph Eur, BP, JP, USP New
102465 Calcium chloride dihydrate EMPROVE®
API Ph Eur, BP, JP, USP New
102367 Magnesium chloride hexahydrate cryst. EMPROVE®
API Ph Eur, BP, JPC, USP New
500111 Cocarboxylase tetrahydrate EMPROVE®
API HY2 / 2021
500112 Cocarboxylase chloride thiamine diphosphoric acid ester chloride EMPROVE®
API HY2 / 2021
500667 Thiamine phosphoric acid ester chloride dihydrate EMPROVE®
API HY2 / 2021
106441 Sodium fluoride EMPROVE®
API Ph Eur, BP, USP HY2 / 2021
106444 Sodium chloride EMPROVE®
API Ph Eur, BP, JP, USP HY2 / 2021
108815 Zinc chloride EMPROVE®
API Ph Eur, BP, USP HY2 / 2021
106143 Meglumine low in endotoxins EMPROVE®
API Ph Eur, ChP, JP, USP HY2 / 2021
128204 Sodium acetate trihydrate EMPROVE®
API Ph Eur, BP, JP, USP, FCC, E262 HY2 / 2021
Expected Availability
Emprove® API Information Packages
32 Emprove® Virtual User Group Meeting | June 1st 2021

33. Technically Unavoidable
Particle Profiles (TUPPs) -
An Update

34. Detailed information for each type of TUP
From Reactive to Proactive
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 Intention, quality policy towards foreign particles
 Flow chart of manufacturing process (reference to MQD)
 TUP information
 Particle picture
 Identity and composition
 Mass balance
 Root cause
 Assessment of additional microbial and BSE risks

35. Detailed information for each type of TUP
Picture and Identity
35 Emprove® Virtual User Group Meeting | June 1st 2021

36. Detailed information for each type of TUP
Picture and Identity
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37. Availability
Technically Unavoidable Particle Profile (TUPP)
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Article Product
100419 Parteck®
M 200 (Mannitol) EMPROVE®
ESSENTIAL Ph Eur,BP,JP,USP,E 421
100494 Parteck® M 100 (Mannitol) EMPROVE® ESSENTIAL Ph Eur,BP,JP,USP,E 421
100892 Sucrose low in endotoxins suitable for use as excipient EMPROVE®
exp Ph Eur,BP,JP,NF
107653 Sucrose EMPROVE®
ESSENTIAL Ph Eur,BP,JP,NF
101816 Ammonium sulfate EMPROVE®
EXPERT ACS,NF
112120 Calcium carbonate precipitated (<= 0.0001% Al) EMPROVE®
ESSENTIAL Ph Eur,BP,USP,JP,FCC,E 170
102064 Calcium carbonate precipitated (<= 0.002% Fe) EMPROVE® ESSENTIAL Ph Eur,BP,USP,JP,FCC
106400 Sodium chloride EMPROVE® ESSENTIAL Ph Eur,BP,USP
116224 Sodium chloride low in endotoxins suitable for use as excipient EMPROVE® exp Ph Eur,BP,JP,USP
137017 Sodium chloride EMPROVE® EXPERT Ph Eur,BP,ChP,JP,USP
106482 Sodium hydroxide pellets EMPROVE® ESSENTIAL Ph Eur,BP,FCC,JP,NF,E 524
137020 Sodium hydroxide pellets suitable for the biopharmaceutical production EMPROVE® bio Ph Eur,BP,JP,NF
108346 D(+)-Glucose monohydrate EMPROVE® EXPERT Ph Eur,BP,USP
141350 Polyvinyl alcohol 4-88 EMPROVE® ESSENTIAL Ph Eur,USP,JPE
141351 Polyvinyl alcohol 8-88 EMPROVE® ESSENTIAL Ph Eur,USP,JPE
141352 Polyvinyl alcohol 26-88 EMPROVE® ESSENTIAL Ph Eur,USP,JPE
141353 Polyvinyl alcohol 40-88 EMPROVE® ESSENTIAL Ph Eur,ChP,USP,JPE
141354 Polyvinyl alcohol 5-88 EMPROVE® ESSENTIAL Ph Eur,USP,JPE
141355 Polyvinyl alcohol 18-88 EMPROVE® ESSENTIAL Ph Eur,ChP,USP,JPE
103583 Parteck® SI 150 (Sorbitol) EMPROVE® ESSENTIAL Ph Eur,BP,JP,NF,JSFA,E 420
115079 Parteck® SI 200 (Sorbitol) EMPROVE® ESSENTIAL Ph Eur,BP,JP,NF,E 420
112635 Parteck® Delta M (Mannitol) EMPROVE® ESSENTIAL Ph Eur,BP,USP,JP,E 421
100493 Parteck® M 300 (Mannitol) EMPROVE® ESSENTIAL Ph Eur,BP,JP,USP,E 421
137112 Poloxamer 188 EMPROVE® EXPERT

38. New
Technically Unavoidable Particle Profiles (TUPPs)
Emprove® Virtual User Group Meeting | June 1st 2021
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Article Product TUPP part of Emprove® OED
105911 Maltose monohydrate EMPROVE® ESSENTIAL Mar 2021
104871 Potassium dihydrogen phosphate cryst., EMPROVE®
ESSENTIAL Ph Eur,BP,JPC,NF,E 340 May 2021
137039 Potassium dihydrogen phosphate cryst. EMPROVE®
EXPERT Ph Eur,BP,JPC,NF May 2021
105101 di-Potassium hydrogen phosphate anhydrous, EMPROVE®
ESSENTIAL Ph Eur,BP,E 340 May 2021
137010 di-Potassium hydrogen phosphate anhydrous EMPROVE®
EXPERT Ph Eur,BP,USP May 2021
106349 Sodium dihydrogen phosphate monohydrate EMPROVE®
ESSENTIAL BP,USP May 2021
137093 Sodium dihydrogen phosphate monohydrate EMPROVE®
EXPERT BP,USP May 2021
106574 di-Sodium hydrogen phosphate heptahydrate EMPROVE®
ESSENTIAL DAC,USP May 2021
137092 di-Sodium hydrogen phosphate heptahydrate EMPROVE®
EXPERT DAC,USP May 2021
106398 Sodium carbonate anhydrous EMPROVE® ESSENTIAL Ph Eur,BP,JP,NF June / July
137012 Sodium acetate trihydrate EMPROVE®
EXPERT Ph Eur,BP,JP,USP June / July
105032 Potassium hydroxide pellets EMPROVE®
ESSENTIAL Ph Eur,BP,JP,NF,FCC,E 525 TUPP to be created

39. Emprove® Suite Notification System
Last but not least
Receive a monthly digest of the updates that were
made in the previous month to:
 Emprove® Operational Excellence Dossiers
 Emprove® Quality Management Dossiers
1 Click on “Be notified of changes to
subscription documents”
2 Submit your name and confirm the notification
3

40. The vibrant M, SAFC, Millipore, Cellvento, and Emprove are trademarks of Merck KGaA, Darmstadt, Germany or its affiliates. All other trademarks are the
property of their respective owners. Detailed information on trademarks is available via publicly accessible resources.
© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.