Our Technology

Upstream Process

For biopharmaceutical production there are two major steps which are designated as upstream and downstream processes. Upstream is the process in which a biopharmaceutical is produced by cell lines manipulated through recombinant DNA technology. The majority of biopharmaceuticals are of protein nature and are expressed in recombinant hosts. For expressing certain biopharmaceutical proteins, microbial and mammalian systems are attractive because of various reasons.

However, there are things microbes simply are not able to do. Many biopharmaceutical molecules are too large and complex to be made by simple prokaryotic bacteria, or even the lower eukaryotic forms such as fungi and yeasts. Complex biomolecules, such as functional mAbs or highly glycosylated proteins like recombinant proteins, require the post-translational metabolic machinery only available in mammalian cells. Glycosylation of monoclonal antibodies and recombinant proteins are important for their biological function and pharmacokinetics. Mammalian cells have become the dominant system for producing recombinant proteins for clinical application because of their capacity to properly fold and assemble proteins and add human like post-translational modifications.

CinnaGen owns the technology of upstream process as per following:

Expression technology which includes high titer cell selection, clone selection, choosing high expression vectors and GMP cell banking system (Working and Master cell banks) Cell growth technology which consists of: culturing the cells with high concentration, different feeding strategy, media optimization and control of glycosylation patterns of proteins expressed by recombinant cell lines. Also we are equipped with two different systems of culturing the cells and manufacturing biopharmaceuticals. One is referred as roller culture system which enables us to manufacture in roller bottles. The other one is state of the art bioreactor systems with different volumes which increase our capacity of cell culture to 15000L. There are a series of them which consists of seed and production bioreactors.

Downstream Process

Meanwhile the second step for biopharmaceutical production is indicated as downstream process which was mentioned earlier. Recovering a biological reagent from a cell culture supernatant is one of the critical parts of the manufacturing procedure for biotech products which includes cell separation, chromatography steps, viral inactivation and final filtration.

Usually, the product subsequently undergoes a series of purification steps. Traditionally, the first step captures and initially purifies the product; the subsequent steps remove the bulk of the contaminants, and a final step removes all trace contaminants and variant forms of the molecule.

These chromatography methods include:

• Affinity
• Ion-exchange
• Cation-exchange
• Hydrophobic interaction
• Gel filtration

Also during the downstream process a viral inactivation procedure is crucial. Here at CinnaGen Co we have gathered the most up to date purification technologies to ensure that the final product meets the defined criteria with high purity and of course high efficiency.

Formulation and Filling

Biopharmaceutical filling processes operate under rigorous aseptic criteria. Aseptic processing describes the final stage of manufacturing, wherein a sterile (aseptic) product is packaged in a sterile container in a clean, controlled environment using methods and technologies that maintain sterility. Product containers are filled and sealed under high-quality environmental conditions designed to minimize contamination.

CinnaGen Co has a full state-of-the-art fill and finish facility, located in three different buildings. We also have almost 10 years of experience with aseptic filling and lyophilization of drug products and excessive experience in filling a wide variety of biotherapeutics. The dedicated filling lines of CinaGen Co. that we can offer is as follows:

• One vial+ one PFS(Prefilled syringes) line in SD1
• One vial+ one PFS(Prefilled syringes) line in SD2
• A cartridge filling line which enables us to produce our drug products as pen in SD4
• (Totally resulting 5 aseptic filling suites)
• Flexible filling volumes between 0.5 mL to 50 ml for vials, 0.5 mL to 1.5 ml for syringes, and 0.5 to 3 ml for cartridges
• Almost fully automated filling machines
• Lot sizes ranging from 1,000 to 75,000

Also we are equipped with two different freeze dryer machines with different capacities. The process of freeze drying can achieve product stability, and improved shelf-life. CinnaGen Co. can provide lyophilization cycle development and optimization services at both clinical and commercial scale.

Quality Control

At CinnaGen's quality control lab we perform accurate and timely testing of various samples(raw material, inprocess, drug substance, drug product and stability  samples) with modern and uptodate equipment and state of the art cGMP compliant methods, to make sure that quality, safety and efficacy of our products meet the highest level possible. Our internal auditor constantly try to keep everything under control with the best quality possible . We give our best effeort to our work and we put our patients first.

Quality Assurance

Our quality activities in Quality Assurance is including all of MANUFACTURING processes which start from the time of receiving raw material and continue until final product which is used by the end user in order to assure of achieving required results. Quality Assurance Dept. of CinnaGen has the responsibility for documentation, Validation, Audit and inspection and batch release and carries out the duties according to the latest PIC/S, ICH and WHO guidelines. CinnaGen was granted ISO 9001 certificate in Quality Management System (in 2000), ISO 13485 in medical devices quality management (in 2005) and INFDQA (Iranian National Food and Drug and Health Quality Award in 2010). During all these years CinnaGen has kept these certificates and also is granted another valuable certificates including ISO 14001, ISO 18001, ISO 10002 and ISO 10015.