Biopharmaceutical Quality Control & Development Laboratory
- PharmD. Alejandro Ricciardi, Technical Director Curriculum Vitae
- Larissa Armas, Technical Assistant
- Diego Charquero, BSc. Biochemistry Curriculum Vitae
- Sofía Horjales, PhD.
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.
Combistats® , EDQM.
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.
B) 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.
C) ANALYTICAL TARGETS
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.
The Quality Control and Development Laboratory of Biopharmaceuticals offers vast experience in methodologies development, bioassays and protein chemistry, as well as a wide range of analytic techniques and lab equipment.
This Lab was conceived to provide solutions in the field of analytical control of Biopharmaceuticals, either using pre-established methodologies by the international guides and pharmacopeias or developing new analytic tools in order to meet and follow the current bioanalytical strategy.
The Lab offers a variety of support services to Biopharmaceuticals products for human use in GLP conditions. Our assays follow the directions established by the ICH guidelines and the FDA and EMA agencies.
From its beginning as analysis laboratory in June 2009, it was named by the Public Health Ministry authorities as the reference lab qualified to perform in-country release testing for Biopharmaceuticals sold in the Uruguayan Market.
The compliance of GLP conditions was not only certified by the government health authorities, but also by several quality audits performed by our clients, both national and international (Current MSP Certification).
The purpose of this Lab belonging to the Institute’s core facilities is to allow the collaboration with other units, thus amplifying the set of analysis to obtain a complete physicochemical characterization of biopharmaceuticals quality properties.
Additionally, it is an advantage to face new regulatory challenges regarding the appearance of biosimilars and to be able to offer a broad analytical platform to perform head to head physicochemical comparability studies against the original therapeutic molecules.
With the recent introduction of new national and regional regulations for Biosimilar pharmaceuticals, the capability to apply analytical tools in order to perform comparability studies plays a substancial role.
Therefore, it is essential to know the state of the art regarding these analytical technologies to evaluate in depth biopharmaceuticals or potential biosimilars. The regulatory health agencies have established three characteristics as priority to identify and analyse in detail biopharmaceuticals, grouped in the following analytical specifications i) possible post-translational modifications; ii) tertiary structure and iii) possible protein aggregates.
Within the Lab’s study object framework – biopharmaceuticals – specific kits and methodologies have been developed on demand. Some examples of these projects are:
i) “Methodology Development to Quantify Host Cell Protein and DNA contaminants in recombinant biopharmaceuticals”. Financed by the National Agency for Research and Innovation: ANII (ALIANZA project between Laboratorio Celsius S.A. and IP Montevideo) (2011-2012)
ii) “Methodological development to quantify generated immunogenicity by Interferon beta1a administration in patients, through cell based and RT PCR bioassays”. Financed by Laboratorio Clausen S.A. (2010)
Moreover, we participated in a multicenter study for the determination of the biological activity of the first filgrastim USP reference standard (2012).
Development of the analytical methodology for the characterization of the N-glycosilated chains of therapeutic proteins using hydrophilic interaction HPLC with fluorescence detection (HILIC-FLD), as well as MALDI-TOF mass spectrometry (Tech transfer from CIGB-CUBA).
EDUCATION – COURSES
Tech transfer for Laboratorio Celsius S.A. (Uruguay) for the filgrastim biological activity bioassay (2009).
Methodological development to quantify generated immunogenicity by the Interferon beta1a administration in patients, through cell based and RT PCR bioassays.Laboratorio Clausen S.A. (Uruguay), (2010).
Biopharmaceutical analytical tech transfer for ConsorcioBiocertifica (Chile), (2010).
Methodology development to quantify Host Cell Protein and DNA contaminants in recombinant biopharmaceuticals.ALIANZA project financed by ANII (National Agency for Research and Innovation) and Laboratorio Celsius S.A. (2011-2012).
Bioassay validation study for fligrastim biological activity for Eurofarma Laboratory (Brasil), (2012).
Physicochemical comparability study between two commercial Abciximab biopharmaceuticals.Laboratorio Libra S.A (Uruguay), 2013.
Tech transfer from Biogen Idec.(USA) for Interferon beta1a biological activity bioassay (2013).
Validation study for peg-fligrastim biological activity bioassay for Eurofarma Laboratory (Brasil), (2014).
Participation in physicochemical comparability studies for the development of a filgrastim-based biosimilar (Fiprima) of Eurofarma Laboratory (Brasil). First biosimilar of original production in Latin America approved by ANVISA (2011 – 2015).
Tech transfer to Eurofarma Laboratory (Brasil) of the analytical methodology to perform the filgrastim and peg-filgrastim biological activity cell-based bioassay, (2016).
Turell L, Botti H, Bonilla L, Torres MJ, Schopfer F, Freeman BA, Armas L, Ricciardi A, Alvarez B, Radi R. HPLC separation of human serum albumin isoforms based on their isoelectric points. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jan 1; 944:144-51.
Manta B, Obal G, Ricciardi A, Pritsch O, Denicola A.(2011). Tools to evaluate the conformation of protein products. Biotechnol. J. 2011, Jun; 6(6):731-41.
Phone: +598 2 5220910
Address: Mataojo 2020 CP. 11400
Montevideo – Uruguay