The Manufacturing process

Preparation of the master cell bank

Bayer employs a well-established, high quality manufacturing process to produce a full length, recombinant factor VIII molecule – KOGENATE® Bayer – for use in patients with haemophilia A.

STEP 1: FVIII gene isolated from the human genome

STEP 2: Plasmid vector containing FVIII encoded DNA integrated into the nucleus of a baby hamster kidney cell line (BHK 21). BHK cells express FVIII

STEP 3: BHK cells are grown and form the basis of the manufacturer's working cell bank

STEP 4: Cells are stabilised for later use by freezing them in liquid nitrogen at -193ºC

STEP 5: Cells are thawed

Large scale manufacturing process

The award-winning system of continuous perfusion fermentation pioneered by Bayer allows for continuous harvesting. The fermentation medium does not contain bovine protein.

STEP 6: Cells are grown in suspension in stirred, deep-tank fermenters under controlled conditions. KOGENATE® Bayer has the shortest protein residence time during fermentation among rFVIII products.

STEP 7: Human Plasma Protein Solution (HPPS) is added to the fermentation medium. The HPPS is extensively purified and tested before it is introduced to the medium. For details of viral and prion reduction click here.

STEP 8: Chromatography purifies the product. Ultra-filtration concentrates the rFVIII molecules of KOGENATE® Bayer

STEP 9: rFVIII molecules undergo a robust purification process that involves extensive chromatography including two viral inactivation steps, all performed at 2-8°C to minimise damage to the rFVIII protein. The process has been validated to show viral and prion reduction .

STEP 10: KOGENATE® Bayer is stabilised, sterile filtered, filled and freeze dried in the final container. No addition of albumin during purification or formulation

The entire manufacturing process to produce a single batch of KOGENATE® Bayer takes just under 200 days.

 

Manufacturing process

To order a video of the manufacturing process please speak to your haemophilia product specialist or > click here

 

Produced by Bayer. This website is intended for HealthCare professionals.
Date of preparation: December 2010 UK.PH.HN.KOG.2010.250.21.3