BIOT 61 |
| The meningitis vaccine (NeisVac-C) is comprised of the de-O-acetylated form of the group C meningococcal polysaccharide conjugated to tetanus toxoid. The polysaccharide purification process includes base treatment and subsequent diafiltration to remove hydrolysed cell impurities. During development, a 100K ultrafiltration membrane was used satisfactorily. Unfortunately, the yield from the first 12 production lots varied from 18 to 100%. Investigation revealed that the ultrafiltration membrane porosity varied with different manufacturer's lots. The corrective action included changing the membrane from 100K to 50K, just prior to our license application. To support the change, we spiked a lab-scale process stream with 200% of the cell impurities and tested the “tightest” 50K membrane available. Even under the worst-case conditions, the impurities were removed to meet the original specifications achieved by the 100K membrane. The change was incorporated into the license application and over 100 lots have since been produced with satisfactory yield and purity. |
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Commercialization of Biologics: Case Studies: Post-Approval Changes & Comparability Challenges
2:00 PM-4:20 PM, Sunday, August 19, 2007 BCEC -- 109B, Oral
Division of Biochemical Technology |