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Collagenase NB for Tissue Dissociation

COLLAGENASE PRODUCTS PRODUCTION COMPLIANT TO GMP

Isolation of Pancreatic Islets Good Manufacturing Practice for Isolation Chromatographically highly purified Production of cells by tissue dissociation as well as tissue Collagenase NB 1 Premium Grade with very low levels of engineering for transplantation into humans require quality secondary proteolytic activities and endotoxins guarantees standards according to GMP guidelines: high yields and viability of isolated cells. Neutral Protease NB • Collagenase NB 1 GMP Grade is an essential additive, and is provided separately allowing individual dosage and high stability of the . • Neutral Protease NB GMP Grade • Collagenase NB 6 GMP Grade Isolation of Sensitive Cells PurifiedCollagenase NB 8 Broad Range is characterized by Such enzymes are regarded to be critical raw materials an increased collagenase activity and reduced levels of other and thus manufactured in compliance with the EU- proteases and bacterial endotoxins. Guide to Good Manufacturing Practice (GMP) for active pharmaceutical ingredients. Moreover, the production fulfils the requirements of TSE (transmissible spongiform encephalopathy) guidelines according to the European Pharmacopoeia

For incoming goods inspection according to GMP, Reference Collagenases are available.

Isolation of Various Cell Types Optimal tissue dissociation can be achieved by using collagenase with a balanced ratio of other proteolytic activities: • Collagenase NB 4 Standard Grade • Collagenase NB 4G Proved Grade • Collagenase NB 5 Sterile Grade

Mild and effective – Collagenase NB 4 Standard Grade for optimal isolation of a broad variety of cells. All Collagenase NB grades are manufactured at the pharmaceutical plant of Nordmark Arzneimittel in Uetersen, Function tested – Collagenase NB 4G Proved Grade is Germany, which is the world’s largest manufacturer of especially suitable for isolation of adipocytes, fibroblasts, collagenase. TSE safety of the fermentation product has hepatocytes, frog oocytes, chondrocytes and stem cells. been certified by the European Authorities, EDQM and by supplier’s certificate of origin. Application of pharmaceutical Ready to use – Collagenase NB 5 Sterile Grade is produced manufacturing standards guarantees a high quality of the under aseptic conditions according to the European products with a reliable lot-to-lot consistency. Pharmacopoeia. PRODUCT INFORMATION

Collagenase Properties Application Pack Size Cat. No. • Chromatographically highly purified • Contains class I and class II collagenases • Isolation of pancreatic islets Collagenase NB 1 • PZ activity* ≥ 3.00 U/mg lyophilisate • Use in combination with Neutral Protease Premium Grade from ≥ 2000 PZ U/Vial S1745503 • Largely free of clostripain, trypsin-like activities NB C. histolyticum and neutral protease • characterization • Endotoxins ≤ 10.0 EU/mg lyophilisate • Enzymatic properties see Collagenase NB 1 • Isolation of pancreatic islets for Collagenase NB 1 Premium Grade transplantation into humans GMP Grade ≥ 2000 PZ U/Vial N0002937 • Manufactured according to international GMP • Use in combination with Neutral Protease from C. histolyticum guidelines NB GMP Grade • Isolation of various cell types e.g. Collagenase NB 4 • Contains class I and class II collagenases and a hepatocytes, cardiomyocytes, pancreatic 500 mg S1745402 Standard Grade balanced ratio of proteolytic activities islets, cells, chondrocytes, tumor cells, 1 g S1745401 from C. histolyticum • PZ activity* ≥ 0.1 U/mg lyophilisate fibroblasts, adipocytes, muscle and 5 g S1745403 epithelial cells, stem cells, gangliocytes • Contains class I and class II collagenases as well as Collagenase NB 4G a balanced mix of neutral protease, clostripain and • Isolation of various cell types – especially 500 mg S1746501 Proved Grade from trypsin-like activities adipocytes, fibroblasts, hepatocytes, 1 g S1746502 C. histolyticum • PZ activity* ≥ 0.18 U/mg lyophilisate chondrocytes, stem cells and frog oocytes 5 g S1746503 • Function tested for cell isolation Collagenase NB 5 • Enzymatic properties see Collagenase NB 4 • Application fields see Collagenase NB 4 Sterile Grade from • Aseptic production according to European 1 g N0002778 • Sterile and thus ready to use C. histolyticum requirements for medicinal products (Ph. Eur.) • Enzymatic properties see Collagenase NB 4 Collagenase NB 6 • Aseptic production according to European • Application fields see Collagenase NB 4 100 mg N0002880 GMP Grade from requirements for medicinal products (Ph. Eur.) • Production of cells as well as tissue 1 g N0002779 C. histolyticum • Manufactured according to international GMP engineering for transplantation into humans guidelines • Contains class I and class II collagenases, and Collagenase NB 8 reduced levels of clostripain, trypsin like activities • Isolation of e.g. cardiomyocytes, 250 mg S1745601 Broad Range from and neutral protease hepatocytes, pancreatic islets, 1 g S1745602 C. histolyticum • PZ activity* ≥ 0.9 U/mg lyophilisate chondrocytes, tumor and thyroid cells • Endotoxins ≤ 100 EU/mg lyophilisate Collagenase N • Contains class I and class II collagenases and other • Reference substance for activity Reference Content proteolytic enzymes ≥ 50 mg S1746301 determination from C. histolyticum • Collagenase activity is regulary re-evaluated Collagenase N • Reference substance for SDS-PAGE • Contains class I and class II collagenases and other Reference Identity analysis, performed for incoming goods ≥ 50 mg S1746401 proteolytic enzymes from C. histolyticum inspection according to GMP • Tissue dissociation Neutral Protease NB • Chromatographically purified neutral protease 50 DMC U/Vial S3030111 • Cell isolation in combination with from C. histolyticum • Activity (DMC assay) ≥ 0.50 U/mg lyophilisate 100 DMC U/Vial S3030112 Collagenase NB • Tissue dissociation Neutral Protease NB • Enzymatic properties see Neutral Protease NB • Cell isolation in combination with GMP Grade from C. • Manufactured according to international GMP ≥ 100 DMC U/Vial N0002936 Collagenase NB GMP Grades for histolyticum guidelines transplantation into humans • Use in ELISA and Western Blot Anti-Collagenase • Specificity against collagenases from C. experiments (C. histolyticum) histolyticum • Immunostaining of tissue 100 μg S5805001 polyclonal antibody • lgG fraction purified by G affinity • Analysis of residual collagenase impurities in from sheep chromatography cell preparations • Use in ELISA and Western Blot Anti-Collagenase • Specificity against collagenases from C. experiments HRP (C. histolyticum) histolyticum • Immunostaining of tissue 100 μg S5805101 polyclonal antibody • lgG fraction purified by affinity chromatography • Analysis of residual collagenase impurities in from sheep • Conjugated with horseradish peroxidase cell preparations

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