Abstract
External and internal differences in pressure of prefilled syringes can cause plunger movement during sterilization, which might cause drug product contamination. Consequently the pressure inside the autoclave during sterilization should be controlled carefully to prevent contamination of the drug product by microorganism and particulates. A previously determined theoretical relationship of temperature to pressure in sealed bottles was modified for prefilled syringes to take plunger movement into account. This modification yielded a correction factor that includes a coefficient of linear thermal expansion for the syringe, thermal expansion of the plunger, and friction between the plunger and the syringe wall. To confirm the accuracy of this modified relationship, 100 mL polypropylene prefilled syringes with butyl rubber plungers, some of which carried pressure and temperature sensors, were used to test various sterilization conditions at the experimental scale. The results showed that the major problem in establishing the pressure conditions for production scale sterilization is temperature distribution throughout the load. However, an over pressure sterilization cycle at 121°C and 0.34 MPa showed the best results. Microbial challenge and light-obscuration particle count tests were performed on the syringes from the worst-case location predicted from modified relationship; the results show that these conditions preserved the sterility of the drug product and protected it from particulate contamination.
Footnotes
- Copyright © Parenteral Drug Association. All rights reserved.
PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.
If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing.
Full issue PDFs are for PDA members only.
Note to pda.org users
The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.