Single Use Technology Integration with Aseptic Connections to Meet Sterility, Dependability, Quality and Traceability! For more information contact Lynzee Perdaris at lperdaris@stiflow.com.

1. Completing the Connection for High Purity Fluid Handling
Lynzee Perdaris
STI Territory Manager
South Carolina
Single Use Technology Integration
with Aseptic Connections
Flow solutions delivered now

2. • Introduction
• Single Use Technology
Manufacturing Integrator
Capabilities
• SUT Aseptic Connections
• Pre Enrollment in the
Quality System and Supply
Chain
Agenda

3. Completing the Connection for High Purity Fluid Handling
Introduction
Single Use Technology Integration
with Aseptic Connections
Flow solutions delivered now

4. Completing the Connection for High Purity Fluid Handling
Single-Use Technology Highlights
 Single Use Technology, SUT, is the most relevant
biopharmaceutical processing improvement today.
 If implemented appropriately, it will dramatically improve
manufacturing productivity, flexibility and security;
will speed product going out to market;
will reduce facility space requirement and operational cost.
 Process development and manufacturing improvement with SUT
requires high level of interaction and commitment where
End User increasingly relies on their SUT supplier.
 The implementation of SUT brings shifts to the traditional quality
systems and supply chain, making adaptation to completely
different assurance concept essential.

5. Completing the Connection for High Purity Fluid Handling
STI Components, Integra Companies and VWR
Integra – Devens, MA STI – Morrisville, NC
Acquired by
• VWR in Nov 2014

6. Completing the Connection for High Purity Fluid Handling
• 60,000 Ft2 Combined
• ISO Class 7 Cleanrooms
• Security of Supply Chain with
multiple sourcing and
manufacturing locations
• Aseptic Processing Expert
Consultation
• Global Manufacturer of Single-
Use Systems & Specialty
Products
• Regional Distributor of Top
Industry Brands
• High Purity, Fluid Handling
Products
• Biopharmaceutical Industry
Focus
• Total Commitment to Customer
Satisfaction & Support
• Quality Leader
• cGMP Compliant
• ISO 9001:2008 Registered
General Capabilities

7. Major Customers

8. Major Customers

9. Completing the Connection for High Purity Fluid Handling
Single Use Technology
Manufacturing Integrator Capabilities
Single Use Technology Integration
with Aseptic Connections
Flow solutions delivered now

10. Completing the Connection for High Purity Fluid Handling
Single-Use Offering
• Custom Single-Use Transfer and
Collection Assemblies
– Product, Buffer & Media Transfer
– Sterile Filtration
– Bioreactor Feed & Harvest
– Chromatography & TFF
– Aseptic Connection, Disconnection
and Sampling
– Bulk Drug Substance Storage
– Sterile Filling
– Other innovative solutions
• Differentiated by QUALITY,
KNOWLEDGE, CHOICE & SERVICE

11. Completing the Connection for High Purity Fluid Handling
Single-Use Capabilities–QUALITY
• Quality
– Quality System certified and
registered to ISO 9001:2008
– Sterility Assurance & Package
Integrity Validation
– Customizable Quality requirements
and Documentation with Product Pre
Enrollment Process
• Regulatory Compliance
– Endotoxin & Particulate Testing
– Complete Personnel Training
– Validation Packages for User
– QRM/QbD; Quality agreements to
enable risk mitigation and supply chain
and process understanding

12. Completing the Connection for High Purity Fluid Handling
Single-Use Capabilities–KNOWLEDGE
• Fluid Handling Expertise
– Connectivity
– Pumps, valves, filters, sensors, etc…
– Aseptic and Sterile Processing
• Single-Use Experience
– Complete Facilities
– Hybrid Facilities
– Self Assembly Conversions
– Components kits
• Innovation and Trends
– Continuous refinement and optimization
of systems and procedures
– ASME–BPE, BPSA, ISPE affiliation

13. Completing the Connection for High Purity Fluid Handling
Single-Use Capabilities – CHOICE
• Unbiased Integrator
– Brand neutral
– Combination of components
from multiple suppliers
• Complete Offering
– Tubing , containers &
Connectors
– Specialty Components
(Filters, Sensors...)
• Fully Custom Systems
– Unique to Application
– Designed to meet User Process
and Quality Requirements

14. Completing the Connection for High Purity Fluid Handling
Single-Use Capabilities – SERVICE
• Technical Support
– Assistance in Process
Development and Design
– Application Specific Testing
and Data
• Customer Service
– Pre & Post Sales Support
– Customizable product ID and
Labels
• Logistics & Inventory
– Custom Packaging
– Stocking Plans

15. Completing the Connection for High Purity Fluid Handling
Aseptic Connections
Single Use Technology Integration
with Aseptic Connections
Flow solutions delivered now

16. Completing the Connection for High Purity Fluid Handling
SU Aseptic Connections - Innovation and Trends
o Innovative SUT Aseptic Connections advance
aseptic processing to higher level of flexibility,
reliability and reduced cost by providing safe,
secure and simple; truly aseptic operation.
o Genderless sterile connectors lead to more
flexibility, faster changeovers and reduces
validation, inventory and operations expenses.
o Pre sterilized SUT process assemblies with
integrated aseptic connectors reduce the use of
highly controlled process environments

17. MISCONCEPTIONS
The right connector can make or break your ability maintain
sterility and prevent your product from leaking.
It can be your last line of defense!

18. Hybrid
SIP
Connectors
Sterile
Connectors
Quick Connects and
Sterile Disconnect
For applications where reliability and sterility are a must
Connect with Colder
Sterile Connect
Sterile Disconnect
Open connections
requiring laminar flow hood
SANIQUIK

19. RECOGNIZED INNOVATOR
Designed to create a sterile connection and disconnection between
stainless steel bioprocess equipment and single-use systems
featuring 3-port design for a true steam-through SIP process

20. STEAM-THRU ® II PROCESS - STEAM ON

21. STEAM-THRU ® II PROCESS - STEAM OFF

23. ASEPTIQUIK® STERILE CONNECTORS
• Easy to Use
- Needs minimal amount of steps to actuate.
- More steps = Higher chance of operator error
• Robust Construction
- Incumbents susceptible to side loads
- Assembly aids and clamps were needed
• Colder Click
- Intuitive steps to make it obvious to users.
• Membrane Pull Tabs
- Ensure simultaneous and secure removal of both membranes
Conducted VOC’s on what was lacking in
the current offerings of sterile connectors.
The result was the initial AseptiQuik.

24. ASEPTIQUIK® STERILE CONNECTORS

25. WE LOVE IT………BUT…….
• Can you make it smaller?
26
• And even easier to use?

26. • Small format – 1/4” flow, smaller profile
• Genderless design – Each half is the same
• “Flip-Click-Pull” assembly – Intuitive design reduces
risk for operator error
• Integrated pull tab protective cover – Ensures
simultaneous and secure removal of both membranes
• Robust construction – Reliable performance without
the need for additional fixtures, clamps or tube welders
• “Colder Click” – audible confirmation of assembly
steps
ASEPTIQUIK® S

27. WE LOVE IT………BUT…….
• Can you make it bigger?
28

28. NEW ASEPTIQUIK® G

29. ASEPTIQUIK® G VIDEO

30. HFC39 STERILE DISCONNECT
• Disconnect tubing while maintaining
a sterile flow path on both sides of
the tubing
• Valved quick connection – flow
shutoff at disconnect eliminating
need for clamps/tube welders
• Sterility of flow path validated with
microbial ingress testing
• 1/4″, 3/8″ and 1/2″ ID tubing

31. ASEPTIQUIK® DC
STERILE CONNECT & STERILE DISCONNECT
Click-Pull-Twist Sterile Connection
One-Step Sterile Disconnect

32. ROBUST SEAL DESIGN – HIDDEN RELIABILITY
• Robust wide format design
• Sterile connection at 1st click
• Will not pull out with membrane
• Seal on both halves provides a secure silicone
squeeze

33. ASEPTIQUIK® TESTING
BPSA – BIO-PROCESS SYSTEMS ALLIANCE
Developed consensus guidelines including these test methods:
• Ingress Testing – Three tests conducted
• Dip – Each pre-assembled half was dipped in challenge organism
and growth media was run through the flow path after assembly
• Spray - Each pre-assembled half was sprayed with challenge
organism then sprayed again during paper removal. Growth media
was run through the flow path after assembly
• Immersion – Completely assembled connector was immersed in
challenge organism with growth media in the flow path
• Ingress tests are done with High/Low/Nominal from OQ
heat weld process

34. ASEPTIQUIK® TESTING (CONT.)
• Helium Leak Rate – Helium forced through an assembled connector to test the
seal integrity
• Flow Test – Determine the flow rate of different configurations
• Burst Test – Ensure that the connector exceeds established pressure rating when
connected
• Tensile Test – Measured the amount of tensile force to cause the connector to leak
or fail while at max pressure (60 psi)
• Creep Rupture Test – Pressured at 2x pressure (120 psi) for 7 days at 40°C
• Biocompatibility (Class VI) – Testing done on PC and Silicone where the
extractions are examined for reaction to the body
• Intracutaneous Injection, Systemic Toxicity, Intramuscular Implantation,
Hemolysis, MEM Elution and Physicochemical Test
• Bacterial Challenge – Organisms loaded in flow path and autoclaved to
prove the organisms were killed
• Extractables – Testing done on PC and Silicone – two solvents (water
and ethanol) at reflux for 24 hours

35. APPLICATION OVERVIEW

36. APPLICATION OVERVIEW
• SUT in the form of pre-sterilized containers, filters, tubing,
connectors and even single use filling manifolds can be integrated
to minimize risks and increase productivity in Fill & Finishing
aseptic and sterile manufacturing.
• This application overview depicts a filling application with a SUT
manifold system with a sterilizing filter transferring the drug product
from a bag to the filling equipment. Pre and post filter integrity
testing capability is provided. Peristaltic pump and clamps are used
to produce and control flow.
ASEPTIC FINAL FILL OPERATION

37. APPLICATION - PROCESS
• Starts when manifold inlet is connected to Bulk Bag discharge with
ASEPTIQUIK, SUT sterile connection.
• Pre filter testing is conducted by wetting the filter with its outlet to a flush
collection bag which is an integral part of the manifold.
• After successful integrity testing, the flush bag is isolated by pinch clamp or
valve, and the manifold/filter outlet is connected to the filler transfer line using
ASEPTIQUIK, SUT sterile connection.
• The transfer line, depending on the type of filler barrier, may use additional
aseptic connection to enter the barrier.
• Inside the filler, if the filling manifold is traditional SST, the transfer line is
connected using STEAM-THRU, SIP Hybrid connection. When there is SUT
filling manifold in the filler, an ASEPTIQUIK, SUT sterile connection is used, or
the transfer line may be integral part of the filling manifold.
• A flow clamp or pinch valve is opened for filtration/transfer to begin.
• For post filter testing, the same pre testing procedure can be used by
ASEPTIQUIK DC sterile disconnecting the transfer line. Or the filter can be
HFC 39 sterile disconnected for separated testing.
• Then throw everything away. No mess. No cleaning.

38. APPLICATION - IMPROVEMENTS
• This application can be improved by integrating proportional pinch
valves to modulate flow.
• Automation?: ARTeSYN® Arterial Process Module is a revolutionary
pinch valve solution for SUT systems, which allow to minimize hold up
volumes while enabling you to automate and regulate the flow like any
modern process control system; with actuators, with pressure sensor
and/or flow meter on close loop to pump speed, to maintain constant
transfer flow independent of filter degradation during filling run
• SUT connection and disconnection enable different subsystems or
alternate systems be combined to created increase flexibility, expanded
capacity or remediation, as for example in this fill application, alternating
fillers, run different batch sizes by adding bulk containers, or replacing
the filter if needed.
• SUT diaphragm valves are now available.
• SUT positive displacement pump heads are also available.

39. Completing the Connection for High Purity Fluid Handling
Product Pre Enrollment in the Quality
System and Supply Chain
Single Use Technology Integration
with Aseptic Connections
Flow solutions delivered now

40. Completing the Connection for High Purity Fluid Handling
Product Pre Enrollment
 What is PeP ?
– A Product Enrollment Package, PeP, is an documentation package, created by STI
with the customer inputs, and pre-approved by Customers, to comply with Product
Realization requirements per ISO 9001:2008. The PeP will ensure that all customer
pre-defined operational and quality attributes, at time of customer in-coming
inspection /release, are known and accounted for prior to first order delivery.
 Why is Product Pre-enrollment Important?
– Product Pre-enrollment ensures that all operational, quality, and delivery related
attributes are accounted for at time of product quote to the customer
– It will provide for regulatory compliance in the implementation of the Single Use
technology in the Biopharmaceutical manufacturing by including consideration of:
 Technical, as well as economic, feasibility
 product and process risk management, process control requirements
 qualification, process validation and material management strategies.

41. Completing the Connection for High Purity Fluid Handling
Product Pre Enrollment (cont.)
 Who generates the PeP?
– A comprehensive knowledge of the customer’s mode of operation and of
Single Use technology’s impact on the customer’s organization are required to
be known for effective Single Use Technologies implementation with
regulatory compliance and operation security.
– Therefore, is an interactive task between:
 End-User’s Quality group, Process Engineering and Purchasing department
 STI Sales, Quality and Engineering
 And if applicable, STI materials supplier
 How the PeP process works ?
– STI Pre Enrollment Checklist Form- 099 is used to gather the most common
required information. Any specific requirement or consideration must be
noted. A Quality Agreement may be executed and made part of the PeP.
http://www.stiflow.com/pre-enrollment-checklist.htm

42. Completing the Connection for High Purity Fluid Handling
STI is a direct distributor for Colder Products Company
Contact Lynzee Perdaris for more information about
Colder Products Company at (803) 508-0825
lperdaris@stiflow.com
Single Use Aseptic Connections,
Transfer & Collection
Flow solutions delivered now