FAQ
Cleaning-in-place
Cleaning-in-place (CIP) removes precipitated material, strongly bound substances and other contaminants from the column bed without dismantling the column.
Regular CIP of the packed column between production batches ensures proper product quality and maintains expected medium and equipment life. An efficient CIP protocol depends on medium in use and the characteristics of the contaminants. Refer to the instructions for each medium, see our literature library.
Sanitization
Sanitization is the reduction of microbial contamination in the column and related equipment to an acceptable minimum. A specific sanitization protocol should be designed for each process according to the type of contaminants present.
Note: Always ensure that columns, systems and auxiliary components are compatible with the chemicals used.
Sodium hydroxide is widely accepted for cleaning empty equipment, cleaning packed chromatography columns (cleaning-in-place , CIP), sanitizing and storing chromatography media and systems.
For CIP, sodium hydroxide has been extensively used to remove proteins and nucleic acids from ion exchange, hydrophobic interaction and gel filtration media. Its use with affinity media is restricted due to the limited stability of affinity ligands. If lipids are bound to a protein, an increased concentration of sodium hydroxide may be required for effective cleaning.
Sodium hydroxide is also effective for inactivating most viruses, bacteria, yeasts and endotoxins. It is common practice in industrial manufacturing to save time by adding salt, e.g. sodium chloride, to the sodium hydroxide solution to combine cleaning with sanitization as well. Since sodium hydroxide is a bacteriostat, it is also useful for storage.
The benefits of using sodium hydroxide include efficacy and low cost, plus ease of detection, removal and disposal.
Precautions
Always ensure that chromatography media, columns, systems and auxiliary components are compatible with sodium hydroxide at the concentration, time and temperatures used. Also keep in mind that sodium hydroxide may be corrosive to both metal and skin.
Compatibility with chromatography media
The concentration of sodium hydroxide used for CIP and/or sanitization will often depend on the level of contamination. For chromatography media, the ability to withstand stringent sanitizing conditions depends on the functional groups, attachment chemistries and the stability of the base matrices to alkaline conditions.
Table 4 in Application Note “Use of sodium hydroxide for cleaning and sanitizing chromatography media and systems” lists the general stability of a wide range of media as a function of pH.
Systems
Systems must be cleaned and sanitized prior to storage. During storage, keep the system filled with 0.01 M sodium hydroxide or 20% ethanol solution.
ystem | Overall height (m) | Footprint (m x m) |
Max. flow rate (L/h) | Min. flow rate (L/h) | Max. operating pressure (bar) |
BioProcess MPLC system 100 | 2.00 | 1.80 x 0.70 | 100 | 10 | 20 |
BioProcess MPLC system 300 | 2.00 | 1.80 x 0.70 | 300 | 30 | 20 |
BioProcess MPLC system 500 | 2.00 | 1.80 x 0.90 | 500 | 50 | 20 |
BioProcess MPLC system 1000 | 2.00 | 2.00 x 0.90 | 1000 | 100 | 20 |
BioProcess MPLC system 1500 | 2.00 | 2.00 x 0.90 | 1500 | 150 | 20 |
BioProcess MPLC system 2000 | 2.00 | 2.00 x 0.90 | 2000 | 200 | 20 |
BioProcess MPLC system 2500 | 2.00 | 2.50 x 1.20 | 2500 | 250 | 20 |
BioProcess MPLC system 3000 | 2.00 | 2.50 x 1.20 | 3000 | 300 | 20 |
BioProcess MPLC system 4000 | 2.00 | 2.50 x 1.20 | 4000 | 400 | 20 |
BioProcess MPLC system 5000 | 2.00 | 2.50 x 1.20 | 5000 | 500 | 20 |
BioProcess MPLC system 6000 | On request | On request | 6000 | 600 | 20 |
BioProcess MPLC system 7000 | On request | On request | 7000 | 700 | 20 |
BioProcess MPLC system 8000 | On request | On request | 8000 | 800 | 20 |
BioProcess MPLC system 9000 | On request | On request | 9000 | 900 | 20 |
BioProcess MPLC system 10000 | On request | On request | 10000 | 1000 | 20 |
BioProcess MPLC system 12500 | On request | On request | 12500 | 1250 | 20 |
BioProcess MPLC system 15000 | On request | On request | 15000 | 1500 | 20 |
BioProcess MPLC system 20000 | On request | On request | 20000 | 2000 | 20 |
System | Overall height (m) | Footprint (m x m) |
Max. flow rate (L/h) | Min. flow rate (L/h) | Max. operating pressure (bar) |
BioProcess HPLC system 12 | 2.00 | 1.20 x 0.70 | 12 | 1.2 | 80 |
BioProcess HPLC system 36 | 2.00 | 1.20 x 0.70 | 36 | 3.6 | 80 |
BioProcess HPLC system 48 | 2.00 | 1.80 x 0.70 | 48 | 4.8 | 80 |
BioProcess HPLC system 60 | 2.00 | 1.80 x 0.70 | 60 | 6.0 | 80 |
BioProcess HPLC system 120 | 2.00 | 1.80 x 0.70 | 120 | 12 | 80 |
BioProcess HPLC system 240 | 2.00 | 1.80 x 0.70 | 240 | 24 | 80 |
BioProcess HPLC system 300 | 2.00 | 1.80 x 0.90 | 300 | 30 | 80 |
BioProcess HPLC system 480 | 2.00 | 1.80 x 0.90 | 480 | 48 | 80 |
BioProcess HPLC system 600 | 2.00 | 1.80 x 0.90 | 600 | 60 | 80 |
BioProcess HPLC system 800 | 2.00 | 2.00 x 0.90 | 800 | 80 | 80 |
BioProcess HPLC system 1000 | 2.00 | 2.00 x 0.90 | 1000 | 100 | 80 |
BioProcess HPLC system 1200 | 2.00 | 2.00 x 0.90 | 1200 | 120 | 80 |
BioProcess HPLC system 1400 | 2.00 | 2.00 x 0.90 | 1400 | 140 | 80 |
BioProcess HPLC system 1600 | 2.00 | 2.50 x 1.2 | 1600 | 160 | 80 |
BioProcess HPLC system 1800 | 2.00 | 2.50 x 1.2 | 1800 | 180 | 80 |
BioProcess HPLC system 2000 | 2.00 | 2.50 x 1.2 | 2000 | 200 | 80 |
BioProcess HPLC system 2500 | 2.00 | 2.50 x 1.2 | 2500 | 250 | 80 |
BioProcess HPLC system 3000 | 2.00 | 2.50 x 1.2 | 3000 | 300 | 80 |
Systems
In general, flushing with 1 M sodium hydroxide for 60 minutes at a moderate flow rate gives efficient cleaning and sanitization. However, system owners
must qualify a cleaning and sanitizing process that is suitable for the application of their system.
Make sure that the process control method for cleaning flushes all possible flow paths in the system. After cleaning, rinse the entire system with water or suitable liquid until the piping system is completely free from cleaning solution (instruments in the system can be used as detectors). Do not leave sodium hydroxide or other cleaning agents in the system.
Caution! pH electrodes are normally not compatible with cleaning solutions. Refer to the manufacturers’ manual in the documentation supplied with the system. If the pH electrode is not in the flow jacket during cleaning, be sure to mount a pH cleaning screw in order to avoid leakage.
BioProcess MPLC and HPLC systems
General documents:
Drawings
Piping and instrumentation diagram
Specifications
Equipment list
Spare parts list
Installation test records
Mechanical documents:
Layout drawings
Picture of system
Separator
Pumps
Valves
Connections
Instruments
Measuring equipment
Electrical documents:
General documentation
Layout
Drawings
Cable list
Pack list
Check-list
I/O list
Component documentation
Fabrication documents:
Operation and test plan
Material certificates
Welding documentation
Certificates
Calibration certificates, test and setting
Configuration of programmable devices
Functional test records
Software documents:
Software configuration description
Software revision document
Manual, including getting started with UNICORN
UNICORN user reference material
UNICORN setup disc
UNICORN strategy disc
Control system documentation:
Monitor
Printer
Computer
Instructions for use (hardware)