When United States Pharmacopeia 60 (USP 60) came into effect little more than a year ago, it added a new dimension to testing for objectionable organisms in pharmaceutical products.
The regulation, which was triggered by a string of Burkholderia cepacia complex (Bcc) infections linked to non-sterile aqueous products, means laboratories are having to build new processes from the ground up.
It is not easy, but compliance does not have to be complicated. Validated microbial limit databases and simple tweaks to common workflows will ensure your products remain Bcc free and USP 60 compliant.
What is USP 60?
December 2019’s USP 60: Microbiological Examination of Non-sterile Products - Tests for Burkholderia cepacia Complex followed a 2017 FDA advisory on the risk of Bcc-contamination in non-sterile, water-based products1.
Bcc, a 21-species strong group of water-borne opportunistic pathogens that are resistant to many antibiotics and can remain viable under harsh processing conditions, can lead to dangerous, potentially fatal complications in vulnerable groups.
In 2005, for example, the Centers for Disease Control was notified of several clusters of Bcc-induced pneumonia linked to a contaminated mouthwash.2
USP 60, then, is about protecting public health therefore non-compliance is not an option – releasing Bcc-contaminated products onto the market can result in a facility being shut down.
How to implement USP 60
Building new processes is never easy and implementing USP 60 has been no exception.
While the regulation addresses the finished product, standard operating procedures (SOPs), must cover each step of the manufacturing process. It is the only way laboratories will be able to understand possible points of entry if contamination is detected.
One way of doing this is using microbial limit testing (MLT) to validate all components, particularly those most susceptible to Bcc growth, and create a baseline dataset. By repeating MLT at every step of the manufacturing pathway, laboratories can develop a solid understanding of how the bacteria react within the process.
Workflows will also need to be adapted. It is worth noting that the biochemical reactions involved in detecting B. cepacia, B. cenocepacia, and B. mutivorans relate to all Bcc species, meaning a single test can confirm the absence of all 21.
Another consideration is the interpretation of positive results. The possible presence of Bcc is indicated by the growth of greenish-brown colonies with yellow halos, or white colonies with a pink red zone on Thermo Scientific™ Burkholderia cepacia Selective Agar (BCSA).3Laboratories must remember, however, that at least pinpoint colony growth should occur within 48 hours, with the color change happening within 48 to 72 hours. Unlike in many similar workflows, then, the process contains two, rather than one, vital observation steps.
Complete for compliance
Building compliance processes from scratch – particularly for a pathogen like Bcc which is present in so many environments – can be challenging.
But with the right preparation and planning, pharmaceutical laboratories can create scientifically robust SOPs that keep non-sterile aqueous products safe, compliant, and on the shelf.