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The leading global supplier of preclinical and cGMP grade
CRM197
WWW.CRM197.COM
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Consistency, Scalability, and Compliance
cGMP manufacturing since 2011
Higher purity than expression in alternate platforms
Kilogram scale manufacturing
Proven clinical results
Amino acid substitution inactivates toxicity
Pfenex CRM197 is a recombinant form expressed in Pseudomonas
fluorescens using the Pfenex Expression Technology™ platform.
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DESCRIPTION
Source: Pseudomonas fluorescens expressed recombinant CRM197
Product Molecular Mass: 58.4 kDa
SPECIFICATIONS
Purity: > 95% CRM197 by SDS-PAGE A and B chain content <
5% of total CRM197
Endotoxin: < 100 EU/mg of protein by LAL method
Dimer: < 5%
CRM197 Carrier Protein Consistency, Scalability, and
Compliance
CRM197 is a non-toxic mutant of diphtheria
toxin1,2 having a single amino acid
substitution of glutamic acid for glycine.
CRM197 is a well defined protein and
functions as a carrier for polysaccharides and
haptens making them immunogenic. It is
utilized as a carrier protein in a number of
approved conjugate vaccines for diseases
such as meningitis and pneumococcal
bacterial infections.
Pfenex CRM197 is a recombinant form
expressed in Pseudomonas fluorescens using
the Pfenex Expression Technology™ platform.
Pfenex CRM197 is identical in both structure
and function to the mutant protein produced
in Corynebacterium diphtheriae. The protein
is available in pre-clinical and cGMP grades
in amounts that will meet any clinical or
commercial requirement.
1. Giannini, G., Rappuoli, R., and Ratti, G. Nucleic Acids Res.
12: 4063-4069 (1984) 2. Mekada, E., and Uchida, T. J. Biol. Chem.
260: 12148-12153 (1985)
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VACCINE DEVELOPMENT JUST GOT A LITTLE EASIER
Highest quality CRM197 commercially available
• Pre-clinical and cGMP grade recombinant CRM197 carrier protein
available3
• Product and process consistency from pre-clinical grade
through cGMP grade
• Speed your vaccine into the clinic
• Avoid slow, complex and costly production in a pathogenic
organism
• Biologics Master File access to support regulatory filings and
the equivalent for ex-US filings
• Cost-effective solution for sourcing critical material for
vaccine development and commercialization
PFENEX CRM197
Conjugation with Polysaccharides
Abso
rban
ce
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
2.2
2.4
Minutes
6.00 6.50 7.00 7.50 8.00 8.50 9.00 9.50 10.00 10.50 11.00 11.50
12.00 12.50 13.00 13.50 14.00 14.50 15.00 15.50 16.00
Pfenex CRM197 is identical to native CRM197.
The conjugation efficiency of Pfenex CRM197 is equivalent to
native CRM197.
Vaccine candidates using Pfenex CRM197 are currently being
evaluated in the US, Europe, and Asia in pre-clinical through Phase
3 trials.
Control CRM197 was produced in Corynebacterium diphtheriae.
IMMUNOGENICITY OF CRM197 CONJUGATES
Rabbit IgG Titers Immunization
Rabbit OPA Titers After Immunization
Conjugate Epitope Density
Native CRM197 A Green 11.7 Native CRM197 B Blue 10.1 Native
CRM197 C Orange 12.1 Pfenex CRM197 Red 11.2
3 The Recombinant CRM197 (bulk) Product has been manufactured as
per the Current Good Manufacturing Practices regulations and
guidances ICH Q7 and ICH Q11, as appropriate, for Recombinant
CRM197 (bulk) as an Active Substance Starting Material intended for
further manufacturing of suitable drug substance and/or drug
product by end user.
10-valent pneumococcal conjugate vaccine using Pfenex CRM197 as
carrierOPA (opsonophagocytosis assay) has been shown to be the best
functional correlate of protection.
Pfenex CRM197 Prevnar®
1 5 6A 6B 7F 9V 14 19A 19F 23F1.0
10.0
100.0
1000.0
SerotypesRa
bbit
IgG
Tite
rs
1 5 6A 6B 7F 9V 14 19A 19F 23F1.0
10.0
100.0
1000.0
Serotypes
Rabb
it O
PA T
iters
Pfenex CRM197 Prevnar®
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PFENEX CRM197 REGULATORY FAQs
Q: Where does Pfenex manufacture CRM197? A: Pfenex CRM197 is
manufactured under cGMP at Serum Institute of India (SII), a
world-class manufacturer of vaccines.
Q: What documentation will I receive with my CRM197 shipment?A:
A Certificate of Analysis is provided for reagent grade orders and
for cGMP orders a Certificate of Analysis and a Certificate of
Origin (stating that no animal-derived components were used in the
manufacture of the product), and recommended storage
conditions.
Q: What supporting regulatory documentation will Pfenex provide
for regulatory filings? A: For regulatory filings in the USA,
Pfenex will provide a Letter of Authorization to allow the FDA to
reference BMF for CRM197. For regulatory filings other than the US
FDA, Pfenex will provide a comprehensive data package similar to
BMF in support of the clients filing.
5 10 15 20 25 30 35 40 45 50 55 60 65 70 75
20
30
40
50
60
70
80
90
100
K36 K3
5
K22
K3’ K
21
K7
K19
K29 K1 K10 K1
8 an
d K3
1
K5
K4K2
”
K9K8
K6
K33
K32
K34
K2’
K32”
80 90 100 110 120 130 140 150
20
30
40
50
60
70
80
90
100
K24
K14
K15
K27
K13
K12
K28
K25
K26
57000 57500 58000 58500 59000
PERC
ENT
0
100 58407
+ Na
Mass th
PERC
ENT
0
100 58407
PFENEX CRM197 COMPARABILITY
Intact Mass Analysis
Control CRM Mass th = 58408
Pfenex CRM Mass th = 58408
LysC Mapping
Control CRM197 Pfenex CRM197
97.4% sequence coverage and are homologous
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10790 Roselle Street San Diego, CA 92121
858 352-4400 www.CRM197.com
© 2018 Pfenex, Inc. All rights reserved. Pfenex, the PFEnex
logo, and Pfenex Expression Technology are trademarks of Pfenex,
Inc. All other trademarks and brands referenced herein are the
properties of their respective holders.
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