BFS technology has great potential in the field of biopharmaceutics because of reduced human intervention during the production
process, convenience, and ease of use offered by its final product in plastic ampul form. The operating conditions of the
BFS process and the nature of plastic ampuls pose many challenges to the stability of biopharmaceutical drug products. Biopharmaceuticals
may experience elevated temperature during the BFS process. CFD could be a useful tool for better understanding the temperature
dynamics during the BFS operation. The unique aspects of BFS operation call for a balanced empirical and systematic approach
during process development and process validation.
Finally, the BFS process may not be suitable for many proteins, especially large, complex proteins with multiple sites for
activity and proteins that are highly temperature-sensitive. In addition, chemical extracts or leachates from the direct
contact between the product and the primary container, as well as volatile chemicals from secondary packaging layers could
act as adjuvants in stimulating an immune response in the patient, which would be of particular concern if the product were
to be injected subcutaneously. These factors should be evaluated and addressed in the early-development phase if plastic ampuls
are selected as the product containers.
1. S.J. Shire, "Stability Characterization and Formulation Development of Recombinant Human Deoxyribonuclease I [Pulmozyme
(Dornase Alpha)]," in Formulation, Characterization and Stability of Protein Drugs: Case Histories, R. Perlman, and Y.J. Wang, Eds. (Plenum Press, New York and London, 1996) pp. 393–426.
2. R. Oschmann, and O.E. Schubert, Eds, Blow-Fill-Seal Technology, (CRC Press, Stuttgart, 1999).
3. N. Rathore, and R.S. Rajan, Biotechnol. Prog. 24 (3), 504–514 (2008).
4. F. Leo, P. Poisson, C.S. Sinclair, and A. Tallentire, PDA J. Pharm. Sci. Technol. 58 (3), 147–158 (2010).
5. European Commission, EU Guidelines to Good Manufacturing Practice. Annex 1, Manufacture of Sterile Medicinal Products (Brussels, Nov. 2008).
6. W. Whyte et al., PDA J. Pharm. Sci. Technol. 52 (3), 89–99 (1998).
7. B. Ljungqvist et al., PDA J. Pharm. Sci. Technol. 60 (4), 254–258 (2006).
8. FDA, Guidance for Industry. Sterile Drug Products Produced by Aseptic Processing— Current Good Manufacturing Practice (Rockville, MD, Sept. 2004).
9. M.H.V. van Regenmortel, K. Boven, and F. Bader, BioPharm Int. 18 (8), 36–50 (2005).
1 0. FDA, Guidance for Industry: Container Cosure Systems for Packaging Human Drugs and Biologics (Rockville, MD, May 1999).
11. EMA, Guideline on Plastic Immediate Packaging Materials (London, UK, May 2005).
12. C.J. Taborsky, E.B. Sheinin, and D.G. Hunt, Am.
Pharm. Rev. 9 (6), 146–150 (2006).