The Biopharmaceutical Quality Control & Development Unit offers vast experience in bioassays and protein chemistry, as well as a wide range of analytic techniques and lab equipment.
It provides solutions in the field of analytical control of biopharmaceuticals, either using pre-established methodologies based on international guides and pharmacopeia, or developing new analytic tools in order to meet and follow bioanalytical strategies. Our assays follow ICH guidelines and the FDA and EMA regulations.
From its creation in June 2009, it was designated by the Ministry of Public Health as a national reference laboratory for the control of biopharmaceuticals sold in the Uruguayan market.
The unit has developed biopharmaceuticals kits and analytical methodologies for the productive sector. An example of this have been the following projects:
Development of Methodologies to Quantify Proteins and DNA Contaminant Derivatives of the Host Cell in Recombinant Bio-Pharmaceuticals. Funded by the National Research and Innovation Agency. (Project ALIANZA – Laboratorio Celsius S.A. and IP Montevideo) (2011 – 2012)
Methodological development for quantification of immunogenicity generated by administration of Interferon beta1a in patients, by means of a Bioassay based on cell culture and Real Time PCR. Funded by Laboratorios Clausen S.A. (2010).
Participation in a Multicenter Study for the Determination of the Biological Potency of the First Filgrastim Standard of the United States Pharmacopeia (USP). (2012)
PA 800 Plus Capillary Electrophoresis (Beckman Coulter)
HPLC Prominence with DAD, RID and Fluorescence detectors (Shimadzu)
Multiskan Spectrum Spectrophotometer and Plate Reader (Thermo Scientific)
Class II, Type A2 Biological Safety Cabinet (Thermo Scientific)
CO2Incubator (Thermo Scientific)
Freezer -20 °C and Fridge (Angelantonni)
PLA® 2.0 , Stegmann Systems.
We carry out Biological Activity assays such as: cell-based bioassays, kinetic assays, and in vivo assays in different species.
Purity assays are performed by HPLC, SDS-PAGE, zone and Capillary Electrophoresis, isoelectric focusing or 2D electrophoresis and either ELISA to quantify protein contaminants or hybridization for DNA contaminants.
Identification assays are done through immunochemistry techniques, peptide mapping, N-glycan profiling and Quantification assays through colorimetric and HPLC techniques.
Institutional Technological Platform for Biopharmaceutical Comparability Studies
The current regulations and international guidelines establish new and rigorous quality requirements to demonstrate biosimilarity among the innovative products already existent in the market and its possible copies.
These requirements are important in a potential biosimilar development stage, to generate scientific evidence supporting the quality, efficacy and safety of the biosimilar to be as close as possible to the reference product.
The comparability study from which biosimilarity should be inferred consists overall in three steps:
1) Physicochemical and biological quality comparability “in vitro”
2) Non-clinical comparability
3) Clinical comparability
The physicochemical and biological characterization is the analytical founding for the development and comparison of the possible biosimilars, and the amount of possible reduction for non-clinical and clinical comparison studies depends of the success in this first stage.
We have experience in biosimilars head to head physicochemical comparability studies in our Lab, together with other platforms of the Institute, following WHO and EMA international guidelines.
Besides the previously described assays, the analytical set for comparability studies include: binding assays, folding assays, characterization and quantification of molecular aggregates, thermal stability, and tertiary structure determination among others.
The current analytical bioportfolio includes the determination of the quality specifications for the following biopharmaceuticals: Interferon-α, Interferon-β, Filgrastim (G-CSF), PEGylated derivates of Interferon and G-CSF, Molgramostim (GM-CSF), Interleukin-2, Erythropoietin, Insulin, Heparin and low molecular weight Heparin, Albumin, Immunoglobulin, Somatropin, Coagulation Factor VIII and certain monoclonal antibodies (Adalimumab, Rituximab and Abciximab).
This is an open list that continues to increase as new technical and technological possibilities are available.
Technological Transfer to Laboratorio Celsius S.A. (Uruguay) for the Biological Activity Bioessay of Filgrastim, (2009).
Methodological Development for the Evaluation of Immunogenicity for the case of Interferon beta 1a, in patients in treatment. Laboratorios Clausen S.A. (Uruguay), (2010).
Analytical Technological Transfer of Biopharmaceuticals to the Biocertifica Consortium (Chile), (2010).
Development of Methodologies to Quantify Proteins and DNA Contaminant Derivatives of the Host Cell in Recombinant Biopharmaceuticals. Project ALLIANCE financed by ANII and Laboratorio Celsius S.A., (2011 – 2012).
Bioessay Validation Study for Biological Power of Filgrastim for the Eurofarma Laboratory (Brazil), (2012).
Physicochemical Comparability Study between two commercial biopharmaceuticals of Abciximab, Laboratorio Libra S.A., (Uruguay), 2013.
Technological Transfer of Biogen (USA) for the Biological Activity Bioessay of Interferon beta 1a., (2013).
Bioessay Validation Study for Biological Potency of Peg-Filgrastim for the Eurofarma Laboratory (2014).
Participation in the Physicochemical Comparability Studies for the Development of a Biosimilar based on Filgrastim (Fiprima) from the Eurofarma Laboratory, Brazil. First Biosimilar of original production in Latin America authorized by ANVISA, (2011 – 2015).
Technological Transfer to Eurofarma, Brazil, of the analytical methodology for the realization of the Biological Activity based on Cell Culture for Filgrastim and Peg-Filgrastim, (2016).