Industry Perspective on the Medical Risk of Visible Particles in Injectable Drug Products

S. Bukofzer, J. Ayres, A. Chavez, M. Devera, J. Miller, D. Ross, J. Shabushnig, S. Vargo, H. Watson, R. Watson
2015 PDA journal of pharmaceutical science and technology  
Sterile injectable products are used extensively in health care. Patients, caregivers, manufacturers, and regulators have an inherent expectation for safe and effective injectable drug products. This expectation requires injectable pharmaceuticals to be produced to standards of quality, purity, and sterility that include being essentially free of extraneous matter such as particles. Despite guidance in producing product that is "essentially free" of particles, manufacturing such product is very
more » ... uch product is very challenging. In many instances, the observation of particles in pharmaceutical products has resulted in product recalls. While medical warnings have accompanied these recall notices, the specifics of these warnings have varied. The medical literature is sparse with respect to case reports and experimental studies providing data to support the safety risk of particles (intrinsic or extrinsic) in humans. A gap exists between the observation of small quantities of particles in injectable pharmaceutical products and patient-documented safety concerns resulting from the inadvertent administration of particles to patients. Thus, a need exists to create a framework to describe and assess the potential risk of administering particles to patients. This paper provides a review of current compendial inspection requirements for visible particles along with a review of the medical literature associated with any observed harm from such particles. Guidance is provided on the assessment of risk in such circumstances including consideration of the following key attributes; patient factors, route of administration and use of filtration at the point of administration, the volume administered, particle size and their fate in body, particle type, source and amount, manufacturing process mitigation and the frequency of detection. Globally, clinicians and patient populations are facing drug shortages in part due to inconsistent product release and recall decisions related to the presence of particles and a lack of understanding of the impact to patient risk. The decision to recall product from the market should be based on context of the manufacturing trend history, complaint rate trending, and medical risk assessment. Unless there are specific special circumstances, there should be no automatic requirement to recall a product lot for a single particle found in a single unit. Notwithstanding high risk clinical circumstances and acknowledging there are limitations to reporting clinical events to particle infusion, the existing data suggest the overall risk to patients is generally low and the benefit of these treatments is generally significant.
doi:10.5731/pdajpst.2015.01037 pmid:25691720 fatcat:mehuv63zk5c3xmbuyt4svkijre