Ever since the development of the earliest intravenous therapies, the presence of particulate matter in injectable drug products has been a concern among clinicians.
The presence of particle contaminants has the potential for patient harm, especially among individuals considered to be in high-risk populations.
In recent years, there has been an increase in the number of drug product recalls due to the presence of particulate matter.
These recalls are actions taken by a company to remove a product from the market. A manufacturer recalls a product voluntarily, by request from the U.S. Food and Drug Administration (FDA) or by FDA order under its statutory authority.
Sources of Particulate Matter
In 2007, reported cases of glass particles found in drug products spurred closer examination of particulates and their possible sources. Particulates found in injectable drugs can include fibers, metals, rubber, glass and even precipitates related to drug products themselves. Particulate matter originating from packaging materials and components has emerged as the major source of particulates in drug products.
While some particles are considered “extrinsic” (i.e., can enter the manufacturing process from outside sources, including personnel), others are “intrinsic” to the manufacturing process specific to a drug product.
Since 2008, there has been heightened attention among manufacturers and regulators on particulate matter detection and control.
With current manufacturing capabilities, it is not possible to manufacture injectable drug products that are completely free of particulates. Thus, minimizing their presence during the manufacturing process is a critical step in reducing their presence in the final drug product, which is a critical factor for the health care professional, the manufacturer and the regulator—and ultimately, the patient.
A Minimum Guideline for Manufacturers
In August of this year, a new standard for visible particulate matter—General Chapter <790>—became official in USP’s compendia of public standards, U.S. Pharmacopeia—National Formulary.
This standard provides manufacturers with procedures and specifications for detecting visible particulate matter and serves as a starting point for manufacturers working with regulators. If a regulatory agency calls for specifications tighter than those provided in <790>—depending upon a manufacturer’s specific product and/or its associated manufacturing process—then a company can work with regulators using the USP standard as a minimum.
Today, manufacturers, regulators and standards-setting organizations like USP continue to work toward manufacturing quality and minimizing harm from particle contamination.
A Growing Understanding of Particulate Matter
With an increasing level of global sourcing and distribution of drug products, attention to the presence and control of particulate matter is more important than ever. Manufacturers must develop and maintain a keen awareness of where their manufacturing processes are most vulnerable to particulate contamination.
To this end, USP is also developing General Chapter <1790>, Visual Inspection of Injections. This standard is designed to give a comprehensive life-cycle approach for understanding particulate matter, where it can come from and how to control it.
USP relies on public comment from critical stakeholders to inform the development of its standards. In early 2015, a proposed version of General Chapter <1790> will be posted for feedback on Pharmacopeial Forum, USP’s free-access online source for posting standards and receiving comments.
We encourage all parties interested in the control of particulate matter in drug product manufacturing and distribution chains to provide their input on this standard, General Chapter <790> and other important USP standards by providing comments on Pharmacopeial Forum.
Desmond Hunt, Ph.D., is a senior scientific liaison at USP for distribution, storage and packaging.