PDA upgrades sterilization standard to meld US/EU specs

By Ryan Cliche

BETHESDA, MD-In 1978, Parenteral Drug Association (PDA), published the Technical Monograph No. 1 (TM 1) standard for validating autoclaves. Industry experts feel this standard is now officially outdated.

TM 1 has been updated and revised to embrace the latest process validation concepts and moist heat sterilization technologies, including air-overpressure and superheated water cascade. The new version, dubbed Technical Monograph No. 1, 2002 Revision Industrial Moist Heat Sterilization in Autoclaves: Cycle Development, Validation and Routine Operation, is intended to harmonize the differences in validation approaches advocated in the U.S. and Europe.

“As the years went by, while the standard wasn't incorrect, we felt there were a lot of nuances of detail missing,” says James Agalloco, president of Agalloco & Associates (Belle Mead, NJ) and chairman of the approximately 30-person task force assigned to rewrite the standard. “These missing details include explanations of how to calculate absolute zero, the availability of computer programs we didn't have years ago and work is now based more on scientific principles.”

There was a great deal of confusion concerning practices across the industry. “Everyone assumed that steam sterilization was a simple, common and universal type of process,” says Agalloco. “We've learned over the years that there is a lot more diversity in the practice. That was one of the things we had to embrace in the new document.”

The U.S. tends to use the bioburden, bioburden/biological indicator (BI) and overkill methods: while in Europe, there is a tendency to only follow the overkill approach. Less heat input to materials results in a longer expected shelf life.
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This diversity has caused equipment to become more specialized. Pharmaceutical manufacturers are now sterilizing plastic bags and liquids not taken into consideration when the original standard was put together.

A diversified group was selected for the task force so that the varying practices would be considered in the revised document. “Basically, [they were selected] for their expertise,” says Agalloco. “We invited all of the members of the original standard's task force we could find as well as people with published works in steam sterilization. We also solicited some of the major companies to find out if they had someone who may be suitable for the task.”

Agalloco says there are basically two schools of thought in the sterilization business. The U.S. tends to have a strong bias towards microbiological demonstration, while the Europeans rely to a greater extent on measurements of temperature and pressure.

Rick Friedman, sterile drugs compliance officer for the FDA, says the Europeans “tend to strongly stress the physical parameters of steam processes, while de-emphasizing the ability to achieve biological kill. Their rationale is if the physical parameters are fulfilled, then they believe the biological kill can be directly extrapolated.” He says the prevailing U.S. viewpoint has been that the physical parameters are important and do normally correlate well with biological kill, but that the real, final proof of process validity is derived from biological data.

“While there isn't a categorical disagreement with the prevailing European stance, they (Europeans) do tend to de-emphasize biological indicators to the point where there has been some debate,” continues Friedman.

This split has made it a challenge to come up with a universal standard. But the pharmaceutical manufacturing industry will benefit from simplified guidelines.

“You don't want to have to have two sets of books to show two different sets of reviewers or inspectors,” says Agalloco. “You want to be able to have a single approach to running the plant and demonstrating how it works.”

Since PDA is not an official standards-setting body, pharmaceutical manufacturers will not be forced to adhere to the revised TM 1. It will be up to the individual companies to adopt the practice.

The task force hopes to unleash the finalized version at PDA's Central Europe Chapter Forum October 21-23, in Basel, Switzerland.

At the event, a collection of speakers and panelists will discuss the standard and teach you how to effectively navigate the guidances and regulations surrounding moist heat sterilization of terminally sterilized products, containers and closures, equipment and porous loads. The panel will also discuss steam quality parameters such as non-condensable gases, dryness fraction as well as superheat and their effects on sterilization efficacy.



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