Biotechnology as a service

We were also directly linked to the structuring and start of activities of the Biotechnology Platform of the company Cristália:

We solved an existing CHO cell growth limitation in wave bioreactor through changes in the process control so that it was possible to reach 30e7 cell/mL, the concentration necessary to carry out the scaling of the process to 500 L (SUB) under GMP certification;

We perform all process parameter calculations for scale-up production and perform staggered cultures in order to maintain the productivity and growth kinetics found in laboratory and pilot scales;

We developed a process for the production of recombinant protein from BHK21, since the clone selection and stable production, and we increased the production from 0.6 mg/L to 60 mg/L by applying statistical tools (DoE);

We diagnosed the cause of variations in the Somatropin production process by E. coli and with the solution proposal based on process control, the process became predictive and stable.

Design of plasmids/vectors for the desired expression system: definition of the type of plasmid/vectors to be purchased from the supplier;

Transformation and cloning: obtaining up to 5 clones for each processing system expression (P. pastoris, E. coli, and CHO);

Creation of the Research Cell Bank (1-18 cryovials of 1-1.5 mL);

Definition of growth kinetics in shaken flasks;

Protein initial expression test;

Purification initial test;

Production of material for in vitro and in vivo studies: production of up to 200 mg of purified protein in the systems defined in the previous steps.

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Adaptation of adherent cells for suspension in fetal bovine serum-free medium;

Creation of cell and virus banks (WCB and MCB);

Characterization of viral production (MOI/POI);

Obtaining kinetic parameters and process validation;

Optimization of culture medium, MOI/POI, purification and formulation;

Scale-up and validation in benchtop bioreactors.

Requirements of the production process of a multipurpose platform to define the architectural design and layout criteria;

Definition of cleaning requirements (CIP and SIP);

Process flow block diagrams (BFD), based on operations production units, for a multipurpose platform;

Mass balance estimation, based on unit operations of the production, for a multipurpose platform;

Equipment organization studies to propose layouts of architecture;

Study of definition of campaigns and suites of different products.

Critical review of the risk analysis of the drug production process in question;

Critical review of the validation report of the production process of the drug in question;

Critical review of the control methods used in the production, purification and formulation process of the drug in question (instrumental and analytical);

Critical review of statistical process control (CEP);

Critical review of the critical process parameters (CPPs) of the unit operations used in the production of the drug in question;

Critical review of the critical quality attributes (CQAs) used;

Critical review of the inquiries made by ANVISA;

Assessment of process and product impurities profile;

Elaboration of a list of actions containing process improvements and strategies to confirm the safety of batches already in stock to be presented at the meeting with ANVISA.

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Technical guidance on the development of the biotechnological process (standardization, optimization, validation and scale-up);

Technical guidance on the development of analytical methodologies.