Because most storage systems are transparent or semitransparent, light sensitivity also can be an issue. Photosensitive drugs or proteins that are activated by light must be specially handled if they are to be stored in a BPC, which will allow in light. Also, the integrity of a BPC must always be visually inspected before use because anything that results in the loss or potential loss of a product is a high-risk investment. Seams tend to be the weakest points and may become brittle and subject to breakage at low temperatures. Also, all ports and tubing on the BPCs must be supported when frozen so that they are not liable to break. The increased dependency on vendors may be seen as a major disadvantage, but this is why it is always beneficial to have a validated backup vendor so that there will always be a continual supply to the manufacturing facility if problems arise.

Another challenge for implementing bulk storage systems is finding satisfactory exterior containers for storing the bulk, both in liquid and frozen state. A viable option that has already been developed at Genentech is an intermediate shipper that is manufactured according to good manufacturing practices and can be frozen along with the bulk. Because the shipping dunnage is already in place as the product is frozen, there are less mistakes and protocols when it comes to transporting the bulk to fill-and-finish facilities. The intermediate shipper with the bulk frozen inside is placed into an external shipper, which can maintain temperature without the aid of dry ice and is also space efficient and disposable.

A further concern that must be taken into account is sampling. Because the bulk fill transfer step from the hold tank into the disposable BPCs is considered an intermediate step, samples must be taken from these bags. The sampling of each pack used can be a highly time-consuming process both on the technician side and for the quality assurance and quality control groups monitoring the samples. If there were fewer bags to manipulate, then there would be less manual manipulations and less sample errors because contact would be minimal. Sampling through a single port at one connection point to fill multiple sample bags would be ideal as taking samples one by one is not as precise and leaves much more room for manual manipulations or inaccuracies. Because sampling requirements will be specific to the product produced and the regulations for its production, a single solution to the industry's sampling needs has not yet been established.

Conclusions

As medicine becomes more personalized toward the patients, drugs must be developed faster and have lower failure during clinical trials. To satisfy both demands, it will become necessary to streamline processes so that multiple drug substances can be quickly and effectively manufactured and turned around. Therefore, disposable bioprocess containers represent not only a sound investment in a current process but also an investment capable of handling the quick changing pharmaceutical environment ahead.

Adam Goldstein is a senior manager, Jacqueline Loesch is a manufacturing scientist, Kellen Mazzarella is a process development engineer, pharma packing and engineering, Tim Matthews is process development engineer and group leader, and Grant Luchsinger and Diane S. Javier are associate engineers, all at clinical operations, Genentech Inc., Oceanside, CA, 760.231.2399, adamsg@gene.com
Luchsinger and Javier were summer interns when this article was written.

References

1.Singh SK. Storage considerations as part of the formulation development program for biologics. American Pharm Rev. 2007;10:03/04.

2.International Safe Transit Association. Guidelines for selecting and using ISTA test procedures and projects. Available from: http://www.ista.org/forms/ISTAGuidelines.pdf.

3.Thermo Fisher Scientific. Characterizations of single-use bioprocess container systems based on HyQ CX5-14 Film. Available from: http://www.thermofisher.com/global/en/home.asp.

4.ER75272 recommended operating Temperature range HyQCX5-14 film. Michael Goodwin and Greg Elgan, Hyclone Laboratories, Inc. Engineering Department (Tg ISTA Testing).