Meningitis Vaccine Purification: Quality Control of Ultrafiltration Membrane Porosity - How to balance porosity, plugging, and lot-to-lot variability in filters. - BioPharm International

ADVERTISEMENT

Meningitis Vaccine Purification: Quality Control of Ultrafiltration Membrane Porosity
How to balance porosity, plugging, and lot-to-lot variability in filters.


BioPharm International
Volume 23, Issue 8

At the time of the yield investigation, the marketing authorization application had been submitted for approval to the Medicines Control Agency (MCA) of the UK. There were communications between MCA and Baxter to finalize the product specifications. The 100 kDa membrane yield problem and the 50 kDa membrane change proposal were communicated to the MCA and the change proposal was accepted.


Table 4. Results from production lots after 50 kDa membrane implementation
The 50 kDa membrane change was implemented in production. For the five subsequent lots, the yield returned to the expected range and the purity was well within the specifications established by the 100 kDa membrane (Table 4).

The size of the GCMP after 100 kDa processing was evaluated as part of the low yield investigation. Based on absolute MW determination by laser light scattering, the MW of GCMP was determined to be 200–300 kDa. A rule of thumb in UF is that the membrane of choice should have a NMWCO one-third to one-fifth of the MW of a product that is to be retained.9 According to this rule, if GCMP sizing data had been available during process development, the 50 kDa membrane would have been a better choice than the 100 kDa membrane.

Since the UF membrane was changed from 100 kDa to 50 kDa, over 100 batches of commercial vaccine have been produced with satisfactory yield and purity.

Throughout the production history, the 50 kDa UF membranes have been reused up to 11 times. Other UF steps have reused UF membranes for up to 26 cycles. Most of the time, UF membranes are retired because they exceed our internal specification of 24-h dirty membrane hold time. Most of the NWP values following cleaning appear to be stable. Because meningitis vaccine purification involves multiple UF steps and each UF step uses multiple UF membranes cassettes, the ability to reuse UF membrane represents a substantial savings in production cost.

CONCLUSIONS

The key lesson learned from the UF yield investigation is that in designing a UF process and validation program, one should consider the sensitivity of the desired separation to variation in the retention profile of different lots of membrane.11 In this case, the UF step was used for concentration and purification of GCMP. The impact of membrane variability on product yield was significant. The impact of this variability on product yield and purity should be evaluated as part of process development and confirmed during process validation.

Shwu-Maan Lee, PhD, is a technical director, Bob Kruse, PhD, is a research scientist, and Amy Robinson, PhD, is a senior research manager, all at Baxter Healthcare, Beltsville, MD, 301.419.8587,
.

REFERENCES

1. Borrow R, Findlow J. Prevention of meningococcal serogroup C disease by NeisVac-C. Expert Rev Vaccines. 2009;8:265–79.

2. Jennings HJ, Lugowski C. Immunochemistry of groups A, B, and C meningococcal polysaccharide-tetanus toxoid conjugates. J Immunol. 1981;127:1011–8.

3. Svennerholm L. Quantitative estimation of sialic acids II. A colorimetric resorcinol-hydrochloric acid method. Biochimica et Biophysica Acta. 1957;24:604–11.

4. Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.

5. Frasch CE. Production and control of Neisseria meningitidis vaccine. Bacterial Vaccines. 1990;123–145.

6. D'Ambra AJ, Baugher JE, Concannon PE, Pon RA, Michon, F. Direct and indirect methods for molar-mass analysis of fragments of the capsular polysaccharide of Haemophilus influenzae type b. Anal Biochem. 1997;250:228–36.

7. Michon F, Huang CH, Farley EK, Hronowski L, Di J, Fusco PC. Structure activity studies on group C meningococcal polysaccharide-protein conjugate vaccines: Effect of O-acetylation on the nature of the protective epitope. Dev Biol (Basel). 2000;103:151–60.

8. Pellicon and Pellicon-2 cassette filters maintenance procedures. 1998;1–19.

9. Millipore Corporation. Protein concentration and diafiltration by tangential flow filtration. Millipore technical brief 2003;1–24.

10. Tkacik G, Michaels S. A rejection profile test for ultrafiltration membranes and devices. Bio Technol. 1991;9:941–46.

11. Parenteral Drug Association. Industrial perspective on validation of tangential flow filtration in biopharmaceutical applications. Parenteral Drug Association Technical Report No. 15. 1992 Suppl; 46:S1–13.


blog comments powered by Disqus

ADVERTISEMENT

ADVERTISEMENT

Pfizer to Acquire Vaccines from Baxter
July 30, 2014
GSK Submits EU Regulatory Filing for Malaria Vaccine Candidate
July 29, 2014
Bristol-Myers Squibb and Ono Pharmaceutical Collaborate on Immunotherapies
July 28, 2014
FDA Accepts First Biosimilar Filing
July 24, 2014
Compounding Pharmacy Issues Recall, But Challenges FDA Decision
July 22, 2014
Author Guidelines
Source: BioPharm International,
Click here