SAFC Bulk Liquid Handling Capabilities

Manufacturing, Packaging and Logistics

A Leading Manufacturer and Supplier of Critical Raw Materials to the Biopharmaceutical Industry

Manufacturing, Packaging and Logistics

Why Choose SAFC?

Critical Raw Material Manufacture and Supply

Raw material management is an ever evolving, increasingly complex and crucial part of any manufacturing process in the pharmaceutical and biopharmaceutical industry. As a leading developer and manufacturer of critical raw materials, SAFC understands the challenges a manufacturing input can bring to process performance, regulatory compliance and business security. Our reputation for safe, productive and consistent raw materials allows customers the confidence needed for component grade, quality and sourcing transparency. SAFC continues to build a progressive portfolio of products and services that contribute to an overall improved process risk profile irrespective of a development, clinical or commercialized stage.

History

Legacy of Expertise

Since 1971, global cell culture-based manufacturing operations have relied on us as a primary supplier for critical raw materials in vaccine, biotherapeutic and diagnostic products. SAFC prides itself on remaining up to date in a dynamic market environment and thus responsive to key industry trends and events:

  • Explosive growth in large molecule drug development where a product is defined by its manufacturing process. SAFC provides excellence in critical raw material supply to ensure consistency of process and product.
  • Transition of an industry traditionally reliant on serum in production processes to the requirement for animal
    component free (ACF) raw materials.
  • Contamination events leading regulatory bodies to place accountability of raw material sourcing in the hands of the drug manufacturer. SAFC is best positioned to assist with supply chain certainty and safety.

Liquid Manufacturing

Capability and Capacity

SAFC continues to progress its cGMP liquid manufacturing facilities and capabilities to meet or exceed current industry requirements. SAFC routinely provides a wide range of bulk liquid lot sizes ranging 50-10,000 L suitable for use in clinical and commercial manufacturing processes.

Dual Liquid Manufacturing Sites
Dual liquid production sites strategically located in North America and Europe have the capacity to support customers with on-going large volume liquid requirements. Both facilities are supported by a single Global Quality System and operated with an aligned local Quality Program.

Global Liquid Media Manufacturing Facilities

 

Facility Europe – Irvine, Scotland N. America – St. Louis, MO (Broadway)
Function Liquid Manufacturing Site Liquid Manufacturing Site
Employees 98 75
Size 118,000 ft2 / 10,963 m2 98,600 ft2 / 9,160 m2
Warehousing 1,450 m2
1,345 pallet spaces
Temperature Mapped
Room Temperature (15-30 °C)
Cold Storage (2-8 °C)
Freezer (-10 to -30 °C)
1,500 m2
2,200 pallet spaces
Temperature Mapped
Room Temperature (15-30 °C)
Cold Storage (2-8 °C)
Freezer (-10 to -30 °C)
Production Scale 50-10,000 L in 316# SS tanks 50-10,000 L in 316# SS tanks
Animal
Component
free (ACF)
ACF Dedicated ACC & ACF (full segregation)
Positive HEPA
Pressure Cascade
Grade A - Aseptic Filling Areas (Bottles)
Grade C - Cleanrooms
Grade C - Hydration
Grade D - Formulation
Closed System Filling Areas
(Bags)
Grade A - Aseptic Filling Areas (Bottles)
Grade B - 2° Cleanrooms
Grade C - Hydration & Formulation
Grade D - Closed System Filling Areas
(Bags)
Filling Capabilities

Bottles: 10 mL - 2 L
Bags: 1 L - 500 & 1,000 L

  • Automated high-throughput bag fills
Bottles: 10 mL - 2 L
Bags: 1 L - 500 & 1,000 L
Cleaning Capability Validated CIP / SIP Processes Validated CIP / SIP Processes
Quality
Certification /
Standard
21 CFR Part 820
ISO9001: 2008
ISO13485: 2003
21 CFR Part 820
ISO9001: 2008
Federal DEA
Missouri DEA
Quality Control
Laboratory
On site On site

Global Quality Systems

SAFC’s liquid media facilities are covered under a comprehensive company-wide Global Quality Management System, which assures the highest product consistency, reproducibility and performance. SAFC is committed to staying at the forefront of all relevant guidelines and regulations and maintains multiple FDA inspected facilities around the world. Our quality systems meet stringent regulatory requirements yet flexible enough to allow a certain amount of customization to meet individual customer requirements. Key attributes include:

  • Dedicated ACF Production
  • Supplier and Material Qualification Programs
  • Risk Assessment
  • 21 CFR Part 820
  • ISO Certifications

Customer Audits
At SAFC we encourage audits by our customers. During your audit we invite you to review and evaluate our many Quality System programs that are designed to maintain product control and allow us to produce high quality products consistently lot after lot.

To schedule an audit please contact your Account Representative.

Quality Control Testing
The SAFC liquid media facilities each have on site Quality Control laboratories. Standard quality control assays for liquid media are conducted using harmonized current compendia methodologies as shown below.

Standard Quality Control Assays for Liquid Media

 

Finish Product Testing(General) Methodology Europe N. America
Appearance Uniformity/color - -
pH USP 791 - -
Osmolality USP 785 - -
Bioburden USP 61 - -
Endotoxin USP 85 (Kinetic Chromogenic, Gel clot LAL) - -
Cell Growth Multi-passage, minimum density and % control - -
Sterility USP 71 - -

Bulk Packaged Water (WFI-grade source)

As a principle ingredient in a vast array of process solutions, SAFC has state of the art WFI (Water-for-Injection) systems you can rely on. Whether a bulk liquid solution or the bulk water itself, SAFC produces a range of large volume liquid products designed for industrial biopharmaceutical use.

Bulk packaged water from these systems is suitable for the preparation of both Upstream and Downstream process solutions intended for further use in industrial bioprocessing applications.

Upstream Application Downstream Applications
• Cell Culture Media • Process Buffers
• Cell Suspension and Wash Solutions • Cleaning and rinsing agents
• Reconstitution of products • Diafiltration and purification buffers

Water System Diagrams



SAFC Cell Culture Grade water is produced from a validated system conforming to current specifications of USP and EP for Water for Injection (WFI). The WFI systems are single generation systems with separate tanks maintained at 80 °C and loops operated at 24 °C. SAFC WFI systems are maintained and monitored on an ongoing basis to ensure water quality standards.

Continuous Monitoring

 

• System • Environmental Program
–– Conductivity –– Microbial
–– Total Organic Carbon (TOC) –– Endotoxin
–– Temperature –– Nitrates

Continuous Quality Control

 

Assay Methodology Specification
Endotoxin Kinetic-chromogenic per USP <85> < 0.25 EU/mL
Bioburden Membrane filtration per USP <1231> < 10 CFU/100 mL
TOC On-line measurement per USP <643> < 500 ppb
Conductivity On-line measurement per USP <645> < 1.0 S/cm
Nitrates Nitrates, EP < 0.2 ppm

Raw Material Sourcing Program

The Supply Chain and Supplier Quality Management teams within SAFC work in a coordinated effort for the sourcing and management of a Global Raw Material Management Program and to ensure the program is robust, controlled and provides for sustainable consistent material supply. These groups within SAFC have two primary initiatives:

Ensuring Security of Supply

  • Maintaining active dialog and relationship with suppliers
  • Establishing working forecast and inventory levels with key suppliers
  • Initiating enhanced Supplier Relationship Management programs

Risk Based Program Mangement

  • Used in the quality assessment, qualification and management for materials, manufacturers and suppliers.
  • Identifying and mitigating supply chain risk to reduce variability
  • Use of subject matter experts to help establish appropriate release criteria and specification
  • Comprehensive change notification from our suppliers through to our customers

Scale-up and Support Service

Small Volume Custom Media: imMEDIAte ADVANTAGE™ Service

SAFC offers global services to make the process optimization phase of your biopharmaceutical development a smooth journey. Fast turnaround of small volume custom media and reliable spent media testing services can assist in effectively reducing your timelines and maximizing your titer.

Efficient Process Development

SAFC established the imMEDIAte ADVANTAGE service to support the biopharmaceutical developer with access to small volume custom media. With a fast turnaround (10 business days*) the service is ideal for:

  • Prototyping / Troubleshooting / Scale-up Studies
  • Upstream / Downstream Materials
  • Powder / Liquid Formats
  • Concentrates

 

Efficient Process Development

Material Feasibility – Scalability - Transferability
Over 50 years of small-scale manufacturing expertise with industrially focused development ensures products are scalable and transferable for GMP readiness. The SAFC Raw Material Sourcing Program ensures a robust, secure supply chain and implements risk mitigation strategies to avoid risk due to potential process or raw material variability – all imMEDIAte ADVANTAGE components fall under this global program.

  • Scale-down model of cGMP powder mill used
  • Compounded from fully released GMP raw materials inventory
  • Batch records
  • Formulation derivatives tracked and archived for reference
Material Feasibility – Scalability - Transferability

Spent Media Analysis

In practical terms, shortened development time relies on having access to dependable data and answers. SAFC’s spent media analysis service offers reliable testing for nutrients that gives customers the data they require to make effective decisions on further process optimization.

  • Results available within 15 business days
  • Discuss data with experts in media development
  • Develop feeding strategies or optimize media based on results

*Not including shipping

Spent Media Analysis

Spent Media Analysis

Assay
Number                    
Assay Components Tested  
Vitamin
Analysis
(88100-1EA)
Water-soluble vitamins in cell culture and fermentation media can be separated, identified and quantified via HPLC. This method is for the accurate determination and quantification of water-soluble vitamins. Cyanocobalamin (B12 )
Pyridoxamine (B6 )
Pyridoxine (B6 )
Nicotinamide (B3 )
Riboflavin (B2 )
Pyridoxal (B6 )
Thiamine (B1 )
 
Lipids/
fatty acids
(88101-1EA)
Lipids are extracted and analyzed by Gas Chromatography. Lipid classes quantified include phospholipids, free fatty acids, triglycerides, cholesterol esters and total protein. Actual values are reported. Lipid Profile                       
Cholesterol
Esters
Phospholipids
Total Lipids Triglycerides
Fatty Acid Profile                  
Arachidonic, Palmitic
Linoleic
Palmitoleic
Myristic
Oleic
Stearic Lauric
Cholesterol
(88102-1EA)
Cholesterol is a critical nutrient utilized during cell growth. Analysis of this nutrient by reverse phase HPLC can provide valuable information to determine cell consumption of cholesterol. Actual values are reported.    
Free Amino
Acids
(88103-EA)
Amino Acids in cell culture media, blood plasma and other matrices can be separated, identified and quantified via Hitachi L-8900 Amino Acids Analyzer. This method is for accurate determination and quantification of amino acids. Taurine
L-Aspartic Acid
Hydroxy-L-Proline
L-Threonine
L-Serine
L-Asparagine
L-Glutamic Acid
L-Glutamine
L-Proline
L-Glycine
L-Alanine
L-Citrullline
L-Valine
L-Methionine
L-Cystine
L-Isoleucine
L-Leucine
L-Tyrosine
L-Phenylalanine
GABA
Ethanolamine
L-Tryptophan
L-Ornithine
L-Lysine
L-Histidine
L-Arginine
Standard
Element - ICP
(88119)
A Varian Vista PRO™ with a radial torch is used for standard elemental analysis and has a relatively wide linear range for many elements. The nebulizer has a very small orifice ~1 mm or less and is easily clogged by high solids. Generally, samples from spent media frequently contain high solids and are cloudy. The solids content should be about 1%. Calcium (Ca)
Magnesium (Mg)
Sodium (Na)
Potassium (K)
Phosphate (P)
Sulfur (S)
Trace
Element - ICP
(88120)
A Varian 720-ES™ with an axially mounted torch gives much lower detection limits than the Vista PRO™. The nebulizer has a very small orifice ~1 mm or less and is easily clogged by high solids. Generally, samples from spent media frequently contain high solids and are cloudy. The solids content should be about 1%. Aluminum (Al)
Barium (Ba)
Bismuth (Bi)
Cadium (Cd)
Chromium (Cr)
Copper (Cu)
Iron (Fe)
Lithium (Li)
Manganese (Mn)
Molybdenum (Mo)
Nickel (Ni)
Lead (Pb)
Stronium (Sr)
Zinc (Zn)
Folic Acid (B9)
(88126-1EA)
Water-soluble vitamin in cell culture and fermentation. Media can be separated, identified and quantified via HPLC. This method is for the accurate determination and quantification of folic acid.   --
Vitamin B12
w/ Folic Acid
(88128-1EA)
Water-soluble vitamins in cell culture and fermentation. Media can be separated, identified and quantified via HPLC. This method is for the accurate determination and quantification of water-soluble vitamins. Cyanocobalamin (B12 )
Pyridoxamine (B6 )
Pyridoxine (B6 )
Riboflavin (B2 )
Pyridoxal (B6 )
Thiamine (B1 )
Folic Acid (B9 )
Glucose
(88202)
Levels are measured by the hexokinase test method. Results provide valuable information regarding glucose consumption during the growth cycle.   --
Endotoxin
(LAL)
Determined by kinetic chromogenic Limulus Amoebocyte Lysate methodology. Endotoxin is released from the cell membrane of Gram-negative bacteria. This test method can be used to evaluate spent and fresh media samples, serum and raw materials.   --
Osmolality
(88206)
Cellular osmolality (pressure) can impact cell performance. Analysis of osmolality in fresh and spent media can assist in optimizing cell culture media for optimal cell performance. Osmolality is determined by freeze-point depression. Results are measured in mOsm/kg H2O. Tests can be performed with or without sodium bicarbonate.   --
pH
(88207)
Cell culture systems require specified pH ranges for optimal cellular performance. The pH of fresh or spent cell culture media is measured with a pH meter. Determination of pH is the (−)log10 of the hydrogen ion concentration of the liquid/liquefied samples. pH can be measured with or without sodium bicarbonate.   --
Bioburden
(88208)
Bioburden testing is performed to monitor bacterial levels using membrane filtration. Actual values are reported.   --
Appearance
(88210)
Appearance is determined by a color wheel for liquids and as a standard OP for dry powders.   --
Solubility
(88211)
This test determines and documents the solubility of raw materials and dry powder media. Satisfactory solubility is defined as fully soluble in water within 30 minutes at approximately 25 °C. The solution is clear and free of particulate. Results are reported as satisfactory or unsatisfactory.   --

Standard Bulk Packaging

SAFC has selected the industry’s leading biopharmaceutical-grade polyethylene-based film, TepoFlex® provided by Meissner as the premier solution for our bulk liquid packaging systems. Innovative in composition, TepoFlex® breaks with the legacy of prevailing films and is one of the most fit-for-purpose films available for biopharmaceutical applications. Manufactured and extruded in ISO Class 7 cleanrooms, the TepoFlex® film is characterized by a comprehensive Leachable and Extractable assessment available for review under confidentiality.

  • Certified animal component-free (ACF)
  • Gamma-irradiated to ensure an SAL of 10-6 substantiated (ISO 11137 methodology)
  • TepoFlex® Film passes biocompatibility according to USP <87>, USP <88>, USP <661>, ISO 10993 parts 5, 6, 10 and 11, as well as EP 3.1.5
Standard Bulk Packaging

1 L Bag

End-ported

Application
Supports sample bag requirements as well as providing connectivity for small volume process equipment.

Connectivity



Port 1 Connection to filling manifold
Port 2 Aseptic sampling port provides for pre-use sampling and low flow aseptic connectivity
Port 3
  • Tubing applicable to pumping operations (size 16)
  • 1/8" x 1/4" tubing widely applicable to tube welder applications
  • Female Luer termination compliments male Luer fitting provided on port number 2

Rigid Outer Container

 

Description SAFC Part # Dimensions Tare Weight QTY per Pallet Count / PKG
Blue Orbis FP
182 Tote
500480 21.8" x 15.2" x 12.9" 6.5 lb. 20 8 x 1 L

5,10 and 20 L Bag

End-ported

Application

Supports sample bag requirements as well as providing connectivity for small volume process equipment.

Connectivity



Port 1 1/8" x 1/4" tubing is widely applicable to tube welder applications - specifically those involving Terumo
welders and aseptic sampling
Port 2
  • Tubing applicable to pumping operations (size 24)
  • Generally applicable to feeding small scale bioreactors <100 L via tubing welder
  • Female MPC connectivity
Port 3
  • Tubing applicable to pumping operations (size 73)
  • Generally applicable to feeding small scale bioreactors <100 L via Male MPC connectivity
  • 3/8" x 5/8" tubing is widely applicable to tube welder applications
  • Port 3 can be connected to Port 2 to form recirculation loop
Port 4
  • Tubing applicable to pumping operations (size 16)
  • Connection to filling manifold
  • Port allows for pre-use sampling and/or supplementation of process fluid

Rigid Outer Container

 

Description SAFC Part # Dimensions Tare Weight QTY per Pallet Count / PKG
Blue Orbis
FP 182 Tote
500480 21.8" x 15.2" x 12.9" 6.5 lb. 20 2 x 5 L
Blue Orbis
FP 182 Tote
500480 21.8" x 15.2" x 12.9" 6.5 lb. 20 1 x 10 L
Blue Orbis
FP 182 Tote
500480 21.8" x 15.2" x 12.9" 6.5 lb. 20 1 x 20 L

50,100 and 200 L Bag

Drum Compatible Assemblies

Application

Incorporates connectivity for the bulk of the larger volume single-use mixers and bioreactors on the market.

Connectivity



Port 1 Connection to filling manifold
Port 2 • Tubing applicable to pumping operations (size 82)
• 1/2" x 3/4" tubing is widely applicable to tube welder applications
• Female MPX connectivity
• Broadly applicable to larger volume mixing and bioreactor applications
Port 3 • Tubing applicable to pumping operations (size 73)
• 3/8" x 5/8" tubing is widely applicable to tube welder applications
• Male MPC provides additional broad applicability to single use systems connectivity
Port 4 • Tubing applicable to pumping operations (size 24)
• 1/4" x 7/16" tubing is widely applicable to tube welder applications
• Aseptic sampling port allows for pre-use sampling and/or supplementation of process fluid
• MPC fittings can be disconnected to provide for applications which require female MPC connectivity

Rigid Outer Container

 

Description SAFC Part # Dimensions Tare Weight QTY per Pallet Count / PKG
Bergen Drum
(50 L)
500628 16" (D) x 27" (H) 8 lb. 5 1 x 50 L
Bergen Drum
(100 L)
500656 20" (D) x 31" (H) 10 lb. 4 1 x 100 L
Bergen Drum
(200 L)
500613 22" (D) x 35" (H) 23 lb. 4 1 x 200 L

100, 200 and 500 L Bag

FlexStation® Compatible Assemblies

Application

Incorporates connectivity for the bulk of the larger volume single-use mixers and bioreactors on the market.

Connectivity



Port 1 Connection to filling manifold
Port 2
  • Tubing applicable to pumping operations (size 82)
  • 1/2" x 3/4" tubing is widely applicable to tube welder applications
  • Female MPX connectivity is broadly applicable to larger volume mixing and bioreactor applications
Port 3
  • Tubing applicable to pumping operations (size 73)
  • 3/8" x 5/8" tubing is widely applicable to tube welder applications
  • Male MPC provides additional broad applicability to single use systems connectivity
Port 4
  • Tubing applicable to pumping operations (size 24)
  • 1/4" x 7/16" tubing is widely applicable to tube welder applications
  • Aseptic sampling port allows for pre-use sampling and/or supplementation of process fluid
  • MPC fittings can be disconnected to provide for applications which require female MPC connectivity
Port 5
  • Tubing applicable to pumping operations (size 82)
  • 1/2" x 3/4" tubing is widely applicable to tube welder applications
  • Male MPX connectivity is broadly applicable to larger volume mixing and bioreactor applications, can
    be connected to port 2 for recirculation mixing/homogenization operations

Rigid Outer Container

FlexStation® compatible – refer to specifications.

  • ISTA 3H Qualified

FlexStations®

Rigid Transport and Shipping Container
Description FlexStation® 100 FlexStation® 200 FlexStation® 500 Volume 100 L 200 L 500 L Outside Dimensions Length 31.9” (809 mm) 31.9” (809 mm) 47.2” (1,200 mm) Width 24.0” (609 mm) 24.0” (609 mm) 31.5” (800 mm) Height 32.8” (833 mm) 32.8” (833 mm) 36.3” (915 mm) Collapsed Height 15.9 (403 mm) 15.9” (403 mm) 18.5” (475 mm) Height (Stacked 2) 64.8” (1,648 mm) 64.8” (1,648 mm) 71.3” (1,810 mm) Footprint 5.4 ft2 (0.5 m2) 5.4 ft2 (0.5 m2) 10.3 ft2 (0.96 m2) Container Capacity 661 lb. (300 kg) 661 lb. (300 kg) 2,860 lb. (1,300 kg) Functional Temperature 0-40 °C 0-40 °C 0-40 °C Material Polypropylene Polypropylene Polypropylene Weight (Empty) 66 lb. (30 kg) 53 lb. (24 kg) 225 lb. (102 kg) Rigid Outer Container These premium rigid transport and shipping containers are available in standard sizes of 100, 200 and 500 liters to fit SAFC’s standard FlexStation® compatible bulk packages. The collapsible containers provide a rugged shipping solution and are also ideal for intra-company use. The durable plastic outer containers are reusable and collapsible for easy storage and handling when not in use. SAFC has qualified for liquid transport in accordance with International Safe Transit Association (ISTA) Series 3 testing.

Accessories
Stainless steel carts and pallet trucks specifically designed for the FlexStation® available. Please inquire with your Account Representative

Rigid Transport and Shipping Container

Rigid Outer Container

 

Description FlexStation® 100 FlexStation® 200 FlexStation® 500
Volume 100 L 200 L 500 L
Outside Dimensions
  Length 31.9” (809 mm) 31.9” (809 mm) 47.2” (1,200 mm)
  Width 24.0” (609 mm) 24.0” (609 mm) 31.5” (800 mm)
  Height 32.8” (833 mm) 32.8” (833 mm) 36.3” (915 mm)
Collapsed Height 15.9 (403 mm) 15.9” (403 mm) 18.5” (475 mm)
Height (Stacked 2) 64.8” (1,648 mm) 64.8” (1,648 mm) 71.3” (1,810 mm)
Footprint 5.4 ft2 (0.5 m2) 5.4 ft2 (0.5 m2) 10.3 ft2 (0.96 m2)
Container Capacity 661 lb. (300 kg) 661 lb. (300 kg) 2,860 lb. (1,300 kg)
Functional Temperature 0-40 °C 0-40 °C 0-40 °C
Material Polypropylene Polypropylene Polypropylene
Weight (Empty) 66 lb. (30 kg) 53 lb. (24 kg) 225 lb. (102 kg)

Shipping and Logistics

Recyclable and Returnable Rigid Outer Containers

Minimizing waste in your supply chain contributes to improved cost efficiencies, a cleaner environment and helps to meet customer demand for sustainable products and services. All SAFC rigid outer containers qualified for use as secondary packaging and transport of bulk liquid are recyclable contributing to reduced waste generation. SAFC offers a comprehensive inventory management program for large scale bulk liquid requirements utilizing the FlexStation® allowing for return and reuse. The reuse of these containers is defined by the recommended number of uses that define a normal FlexStation® lifespan.

 

Recyclable Totes and Drums Reusable FlexStation® Container
  • Blue Orbis Tote (NA)
  • Bergen Barrel (NA)
  • FlexStation® (NA & EU)
  • Blue Orbis Tote / Bergen Barrel (EU)
   

Optional use of a dedicated FlexStation® fleet is available through the SAFC Recyclable and Reusable Program.
This alternative allows customers to identify and track customer-specific containers allocated to their business
offering expanded flexibility and control for continuous large volume supply needs. Please see your local account
representative for more information.

Inventory Identification and Tracking

  • Container Ownership
  • Lot-specific Designation
  • Track Number of Uses (cycle count)

Maintenance

  • Clean Out-of-Place Protocols
  • Controlled Storage

Optional Customer-own Containers

  • Ideal for Ongoing Large Volume Supply
  • Increase Flexibility
  • Increased Control
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