Defining terms for safer drugs
The U.S. Pharmacopeial Convention (USP) published its Chapter <790> guidance in 2014, providing much-needed clarification on a critical subject: what it means for a parenteral (injectable) medical product to be “essentially free” of visible particulate matter.
Examples of such contaminants include fibers, metal, rubber, glass, and even precipitates related to the drug products themselves. Visible particulates fall into two main groups according to their source:
- Extrinsic particles enter the manufacturing process from outside sources including personnel and packaging materials
- Intrinsic particles arise from the manufacturing process itself and are specific to a particular drug product
Previous USP guidelines left the phrase “essentially free” open to some interpretation, leading some in the industry to assume this meant a product with zero defects—a laudable goal, but not a practical or well-defined standard of quality. USP <790> provides a more specific definition of the phrase, along with a strategy for conducting the visual inspections for quality assessment, stating that manufacturers should:
- Inspect clear containers without magnification over a backlight intensity of between 2000–3750 lux
- Inspect for light-colored particles against a dark background and darker particles against a light background
- Invert or swirl the container to induce movement of any particulates, allowing for easier detection
- Visually inspect 100% of samples
- Conform to an Acceptable Quality Limit (AQL) of ≤ 0.65%
It should be noted that USP develops and publishes standards for drug products, but has no role in enforcement of these standards, which is the responsibility of US FDA and other government authorities. As such, USP <790> is intended to provide the industry with a common reference, along with defined targets for compliance that facilitate discussions with the FDA related to legal acceptance criteria for drug quality assurance.
“Citizen Petition.” FDAnews, https://www.fdanews.com/ext/resources/files/04-15/04-17-15-particulatespetition.pdf.
“Getting Particular About Particulates How Can You Avoid Becoming The Next Recall.” Pharmaceutical Manufacturing Resource, https://www.pharmaceuticalonline.com/doc/getting-particular-about-particulates-how-can-you-avoid-becoming-the-next-recall-0001.
“Legal Recognition – Standards Categories | USP.” U.S. Pharmacopeia, https://www.usp.org/about/legal-recognition/standard-categories.
Shabushnig, Ph.D., John, and Hirohito Katayama, Ph.D. “Japanese Pharmacopeia (JP) and United States Pharmacopeia (USP) Developments in Visual Inspection for Foreign Particulate Matter.” J-Stage, https://www.jstage.jst.go.jp/article/pda/17/1/17_94/_pdf/-char/ja.