Technically unavoidable particles (TUPs) are found in chemical raw materials, such as excipients. If not identified as being innocuous, they can lead to entire raw material batches being rejected — unnecessarily and often at high costs — by users.
Still, there are no official guidelines available regarding how to deal with these foreign particles. Proactively managing and communicating TUPs with the help of dedicated TUP profiles could be the answer.
The presence of foreign matter in excipients and other chemical raw materials is typically considered to be a threat to the final pharmaceutical product’s quality. In fact, particles can endanger patient safety. They can also violate compendia and regulatory requirements, disrupt supply chains, lead to drug shortages and harm a company’s reputation. However, not all particles are dangerous.
Technically unavoidable particles (TUPs), as defined by International Pharmaceutical Excipient Council (IPEC), which can arise during excipient manufacturing, handling or packaging, neither pose a higher risk to patient safety, nor do they affect the efficacy or quality of the drug product.
The goal is to inform customers about the presence of TUPs and to provide details on the corrective and preventive action (CAPA) taken and the mitigation strategies that are used. The root cause analysis on the particles’ source saves customers time and resources and enables them to independently assess the potential impact of particulate matter in their products.
The first step in preparing a TUP profile consists of analysing the situation. This includes inspecting batches and evaluating complaints.
Once the TUPs have been detected, assessed and inspected, the corresponding guidelines (if available) are reviewed.
When it comes to metal impurities, for instance, the ICHQ3D guidelines for elemental impurities are a good starting point.
Step two consists of a root cause analysis to identify the origin of the particles. Can they be avoided entirely or at least reduced?
The last and very important step regarding TUP profiles is communicating and collaborating with stakeholders. Establishing a standardised process to handle typical and atypical particles is highly recommended.
TUP profiles should always include information on the size, composition and expected number of particles. Ideally, each profile should be linked to a flowchart of production processes.
Moreover, information on solubility as well as known guideline limits, should be provided. As best practice examples, mitigation strategies should also be included when applicable.
References: IPEC - Technically Unavoidable Particle Profile (TUPP) Guide
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