Products > Crystallization Screens > GRAS Screens > GRAS Screen™ 1 • GRAS Screen™ 2
GRAS Screen™ 1 • GRAS Screen™ 2
Applications
- GRAS reagent crystallization screen for proteins, including monoclonal antibodies, where Polyethylene glycol is the primary, and Salt the secondary reagent, sampling pH 4-9
- Identify GRAS based reagents that promote crystallization of biotherapeutics for bioprocess, bioformulation, and continuous flow manufacturing applications
Features
- Developed at Hampton Research
- Generally Recognized As Safe reagent formulation
- Samples pH 4.0 - 9.0 without an added buffer
- Primary crystallization reagent:
- GRAS Screen 1: PEG 300, 400, MME 550, & 600
- GRAS Screen 2: PEG 1,000, MME 2,000, 3,350, & 4,000
- Secondary crystallization reagent:
- 24 unique salts
- Compatible with Vapor diffusion, microbatch, free interface diffusion
- Reagents soluble between 4°C and 30°C
- Antibody crystallization screen
- Membrane protein crystallization screen
- LCP compatible
Description
GRAS Screen™ 1 and GRAS Screen™ 2 were developed by Hampton Research for the crystallization of proteins, including monoclonal antibodies.
Each of the chemicals in GRAS Screen 1 and 2 have been used under one or more of the following categories. As (1) a Generally Recognized As Safe (GRAS) substance, (2) a pharmaceutical excipient, (3) a normal physiological constituent, (4) a metabolic byproduct, and/or (5) a Everything Added to Food in the United States (EAFUS) substance.
Formulation is based on a) data mining databases such as the Protein Data Bank (PDB), BMCD, and in house Hampton Research data, b) review and analysis of the patent and scientific literature, c) input from academic and pharma colleagues, and d) in house testing.
The primary crystallization reagents in GRAS Screen 1 and 2 are Polyethylene glycol 300, 400, MME 550, 600, 1,000, MME 2,000, 3,350 and 4,000 (high concentration) versus 24 unique secondary salts (low concentration), sampling pH 4 to 9 without an added buffer. The screens can be considered an extension to the PEG/Ion screens, albeit with a focus on GRAS reagents.
GRAS Screen 1 samples four low molecular weight Polyethylene glycols (300, 400, MME 550, and 600) versus twenty-four salts, encompassing pH 4-9. GRAS Screen 1 is supplied in a 96 Deep Well block format and is compatible with robotic and multi-channel pipet liquid handling systems. GRAS Screen 1 is compatible with vapor diffusion, free interface diffusion, and microbatch crystallization methods. For research use only.
GRAS Screen 2 samples four medium molecular weight Polyethylene glycols (1,000, MME 2,000, 3,350, & 4,000) versus twenty-four salts, encompassing pH 4-9. GRAS Screen 2 is supplied in a 96 Deep Well block format and is compatible with robotic and multi-channel pipet liquid handling systems. GRAS Screen 2 is compatible with vapor diffusion, free interface diffusion, and microbatch crystallization methods. For research use only.
Support Material(s)
HR2-451 GRAS Screen 1 Documents HR2-451 GRAS Screen 1 SDS HR2-452 GRAS Screen 2 Documents HR2-452 GRAS Screen 2 SDS
GRAS Screen 1 & GRAS Screen 2 Formulation & Scoring Data
Related Item(S)
References
1. Optimization of crystallization conditions for biological macromolecules. Alexander McPherson and Bob Cudney. Acta Crystallographica Section F Volume 70, Issue 11, pages 1445-1467, November 2014.
2. Crystallization of intact monoclonal antibodies. Harris LJ, Skaletsky E, McPherson A. Proteins. 1995 Oct;23(2):285-9.
3. Crystalline monoclonal antibodies for subcutaneous delivery. Yang MX1, Shenoy B, Disttler M, Patel R, McGrath M, Pechenov S, Margolin AL. Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6934-9.
4. Fast and Scalable Purification of a Therapeutic Full-Length Antibody Based on Process Crystallization. Dariusch Hekmat et al, Biotechnology and Bioengineering, Vol. 110, No. 9, September, 2013.
5. Towards Protein Crystallization as a Process Step in Downstream Processing of Therapeutic Antibodies: Screening and Optimization at Microbatch Scale. Yuguo Zang et al, PLoS One. 2011; 6(9): e25282.
6. Crystallization as a tool for bioseparation. Bob Cudney, Am Biotechnol Lab. 1994 Jun;12(7):42.
7. Large-scale crystallization of proteins for purification and formulation. Hekmat D. Bioprocess Biosyst Eng. 2015 Jul;38(7):1209-31. doi: 10.1007/s00449-015-1374-y
8. Using X-Ray Crystallography to Simplify and Accelerate Biologics Drug Development. Brader ML, Baker EN, Dunn MF, Laue TM, Carpenter JF. J Pharm Sci. 2017 Feb;106(2):477-494. doi: 10.1016/j.xphs.2016.10.017.
9. Excipients and Their Role in Approved Injectable Products: Current Usage and Future Directions. Sandeep Nema and Ronald J. Brendell, PDA J Pharm Sci and Tech 2011, 65 287-332.
