In Search of a Sterile Fill - Pharmaceutical Technology

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In Search of a Sterile Fill
Technological developments make it easier to manufacture sterile parenterals.


Pharmaceutical Technology
Volume 34, Issue 3, pp. 46-50

Close the door on open vials

Technology such as disposable components and isolators has improved the degree of sterility assurance possible during the filling of open vials. The vials' own design, however, leaves the product susceptible to airborne contaminants that could be introduced during the filling process.

A closed vial developed by MED-Instill was designed to eliminate the need for filling open containers. The company used an olefin polymer base to create its Intact closed vials. Robotic arms produce the vials in a closed, aseptic, and controlled environment that protects against viable and nonviable particles until the vials' closures are in place. After the vials are closed, they are sterilized by electron beam, gamma irradiation, or pulsed light, depending on the sensitivity of the formulation to be filled. The closure's primary seal is completely controlled while the vial is empty and the seal cannot trap product. MED-Instill originally closed the vials with a specially formulated thermoplastic elastomer (TPE), but has since developed and validated new materials that provide stability for more formulations.

MEDInstill also developed a filling machine specifically for its Intact vials. Inside the machine, a noncoring needle pierces each preassembled closed container and fills it with product. After the needle is withdrawn, a laser seal or a novel material-sealing mechanism ensures that a totally hermetic seal is maintained during the container's shelf life. This filling system "is at least 10,000 times safer than most aseptic filling technology," says Daniel Py, founder and chairman of MEDInstill. The technique does not require isolators because the Intact containers themselves act as isolators, he adds.

MEDInstill's closed-vial system is "a game-changer," says Agalloco. "The potential for contamination in that system is extremely low. It's got to be one of the safest containers available for sterile products," he says. The fact that the containers are made sterile completely changes the way manufacturers handle them in their facilities. "You don't have to have a stopper washer, a glass washer, a steam sterilizer for stoppers, or a dry-heat tunnel for glass depyrogenation," Agalloco says. The containers thus reduce the amount of utilities and equipment that manufacturers need for filling. The closed vials also eliminate the possibility of mishandling and prevent cross contamination.

MEDInstill's filling system also removes the need for human intervention. Validation studies have shown that little or no environmental control is required during filling to protect against viable and nonviable particles and cross contamination, says Py. Even when operators spray microbial contaminants into the Intact filling tunnel, the Intact containers are filled sterile. The system also greatly reduces the amount of quality-control operations needed, which led FDA agents to remark that MEDInstill had engineered regulatory compliance into the Intact technology, according to Py.

MEDInstill licensed their original system for vaccines and injectables to Aseptic Technologies, a Belgian company owned by GlaxoSmithKline (London).

Conclusion

The high standards for sterility and purity have long challenged makers of injectable drugs. Technological innovations and new process designs promise to reduce operator interventions, shield products and containers from foreign particles, and allow equipment to be dedicated to specific drugs. Although manu-facturing parenteral drugs is not easy, these advances allow companies to ensure sterility to a greater extent, and with greater efficiency, than was previously possible.


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