Challenges and Innovation in Aseptic Filling: Case Study with the Closed Vial Technology

  • Benoît Verjans
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 6)


Aseptic filling of injectable drugs is one of the most critical manufacturing processes in the pharmaceutical manufacturing industry as it presents a significant risk for the patient in case of bacterial contamination. Therefore, a series of constraints are imposed to the manufacturers, leading to a very complex process requiring intensive validation, training and care during operation. To optimize this process, several improvements have been made, focusing on (1) the design of pharmaceutical facilities to ensure an optimal environment for the filling area, (2) optimal gowning of operator, and (3) separation of the operators from the filling area. Regarding containers, the pharmaceutical industry disposes of a wide range of solutions to aseptically fill injectable products. The most classical ones such as ampoules and vials are now challenged by new technologies which offer several advantages to the pharmaceutical manufacturer, to the healthcare practitioner and/or to the patient. Four recent technologies came to the market in the last decades, all of them with their own profile of advantages: on one side, the prefilled syringe and the cartridge which provide a ready-to-inject solution to the practitioner and the patient; on the other side, the blow-fill-seal container and the Closed Vial technology which offer a safer solution and an easier solution for the manufacturer. In this article, these new solutions are compared to the well-established ones and their profiles of advantages and disadvantages are detailed.


Clean Room Healthcare Practitioner Water Vapor Transmission Rate Product Path Filling Area 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Active pharmaceutical ingredient




Colony forming unit


Contract manufacturing organization


Cycloolefin copolymer


Cycloolefin polymer


European Medicine Agency




Food and Drug Administration


Overall exposure limit


Prefilled syringe


Restricted Access Barrier System


Standard operating procedures


Thermoplastic elastomer


Vapor hydrogen peroxide


Water for injection


  1. Agalloco J, Ackers J (2010) Advance aseptic processing technology. Informa Healthcare, New YorkGoogle Scholar
  2. Agalloco J, Akers J (2005) Aseptic processing supplement. Pharm Technol 29:S16–S23Google Scholar
  3. Eudralex (2008) Annex 1. Manufacture of sterile medicinal products (corrected version), vol. 4 (applied in 2009)Google Scholar
  4. Lee F (2007) Pharmaceutical engineering, vol 27 no. 3, pp 1–10Google Scholar
  5. Lysfjord J (2009a) Practical aseptic processing—fill and finish. Davis Healthcare International, River GroveGoogle Scholar
  6. Lysfjord J (2009b) Practical aseptic processing—fill and finish. Davis Healthcare International, River Grove, pp 247–272Google Scholar
  7. Lysfjord J (2009c) Practical aseptic processing—fill and finish. Davis Healthcare International, River Grove, pp 273–293Google Scholar
  8. Mackler S (2004) Environmental monitoring: Portide counts are easy. Bioprocess international, pp 2–7Google Scholar
  9. Reed C (2002) Recent technical advancements in blow-fill-seal technology. In: Business briefing: pharmagenerics, pp 1–4Google Scholar
  10. Thilly J, Conrad D, Vandecasserie C (2006) Aseptic filling of closed, ready to fill containers. Pharmaceutical engineering, vol 26. pp 66–74Google Scholar
  11. Verjans B, Thilly J, Vandecasserie C (2005) Aseptic processing supplement. Pharm Technol 29:S24–S29Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  1. 1.Aseptic TechnologiesGemblouxBelgium

Personalised recommendations