Animal-Component Free Process (ACFP) Statement

All stages of R&D Systems Animal-Component Free Process (ACFP) product line, manufactured in an Sf 9 insect cell line, include the following:

Standard Operating Procedures: Every stage of R&D Systems ACFP product manufacturing employs Standard Operating Procedures (SOPs). SOPs provide traceability of raw materials and help to assure consistency from lot to lot and guarantee the highest quality products.

Deviation Systems: Our quality assurance protocols involve deviation systems, which ensure that any non-conforming products (i.e., those that do not meet the requirements outlined below) are identified at the earliest opportunity. All deviations are reported, investigated, and recorded.

Each stage of our established protein production and purification methodology has been modified for manufacture using ACFP raw materials and labware.

1. Cell Line:
   1. Certified Sf 9 insect cell line: grown for several passages in an animal-free medium, after which, a large cell bank was made. 
   2. Extensive testing was done on the bank to certify the lack of cytopathogens by screening for various viruses, Mycoplasma, and Sporiplasmas using both in vitro and in vivo testing methods.
2. Molecular Biology:
   1. Molecular Biology processes follow approved SOPs.
   2. Raw materials and labware are animal-free* (see below).
   3. DNA was phenol:chloroform extracted.
   4. Transfections were done using the certified cell line and animal-free components.
   5. Protein specific cell lines were then generated using only components that were deemed animal-free.
   6. Cell lines are stored in a dedicated ACFP Dewar.
3. Cell Culture:
   1. Cell culture processes follow approved SOPs.
   2. Raw materials and labware are animal-free* (see below).
   3. All cell culture processes were performed in a dedicated animal-free hood.
   4. All labware is dedicated to the ACFP processes.
4. Purification:
   1. Purification processes follow approved SOPs.
   2. Raw materials and labware are animal-free* (see below).
   3. Dedicated animal-free columns are used.
   4. Column cleaning procedures have been validated.
   5. Bulk purified proteins are filtered using certified animal-free filters.
5. Bottling/Labeling:
   1. Line clearance procedures ensure all relevant areas are cleared of materials from the previous operation before filling commences.
   2. Lyophilization is conducted separate from animal-derived products.
   3. Vials and stoppers or liners are animal-free.
6. Documentation:
   1. Certificate of Analysis is available upon request.
   2. Certificate of Origin is available upon request.

*Additional Information for Lab Supplies

1. We ensure that lab supplies containing animal-derived materials meet the requirements necessary to inactivate Bovine Spongiform Encephalopathy (BSE) and Transmissible Spongiform Encephalopathy (TSE). Any peripheral supplies employed must: a) meet international requirements for minimizing the transmission of animal spongiform encephalopathy, and b) be subjected to rigorous BSE/TSE inactivation procedures.

   At this time, some of the peripherals used in R&D Systems animal-free production processes may be made of plastics that contain or come in contact with animal-derived substances. These materials must meet one or more of the following criteria regarding the transmission of animal spongiform encephalopathy:

   • EMEA 410/01 Rev 2 Oct 2003.
   • Regulation (EC) 1774/2002, Annex VIII, Chapert IV, A, 3(a)(ii).
   • FDA 9CFR 94.18.

Treatment of Lab Supplies to Inactivate BSE and TSE

1. Letters are on file from the relevant manufacturers stating that supplies from outside vendors have undergone at least one of the following rigorous methods that are recognized for the inactivation of BSE and TSE:
   • Sterilization: at 200 °C.
   • Heat Inactivation: material is subjected to temperatures of greater than or equal to 95 °C for greater than or equal to 3 hours.
   • Trans-esterification or hydrolysis: material is subjected to a temperature of greater than or equal to 200 °C under appropriate corresponding pressure for greater than or equal to 20 minutes.
   • Saponification: material is subjected to 12 N NaOH.
   • Continuous process: material is subjected to temperatures of greater than or equal to 140 °C under pressure (2 bars) for greater than or equal to 8 minutes or equivalent.

Operational Excellence

In our continuing efforts to provide our customers with the highest quality proteins produced under stringent conditions, we will continue to search for animal-free replacements for the above mentioned peripherals and substitute these whenever possible.