Risky Business: Toxicological Risk Assessments to Support Product Safety

Extractables, leachables, impurities, degradants, contaminants – what else can go wrong?

20 January 2015

A challenge often faced by pharmaceutical, biotechnology, and medical device companies is the assessment of risk due to exposure to various substances that may be present in a given product.  This is equally true for products in the early stages of development and for those which are already marketed and available to patients.  A toxicological risk assessment is an important tool that can be used to address this issue.

Toxicological risk assessments are conducted in one of two ways.  The first is a proactive approach in which the safety of a given substance is evaluated prior to exposure.  This approach is used as a tool to identify substances of concern and, if necessary, establish specification limits for them.  The second is a reactive approach that similarly evaluates the safety profile of a given substance, but then uses this information to determine the risks associated with an exposure that might already have occurred.  Both of these approaches can be used to determine risks associated with exposure to residual solvents, process impurities, leachables and extractables, degradants, contaminants (including cross-contaminants from shared production lines), and other substances that are not intended to be present in a given drug product.

Once a substance of concern is identified, the risk assessment begins with the collection and analysis of relevant nonclinical and clinical information related to the safety of the substance.  Such information is obtained from the published scientific literature, databases maintained by regulatory agencies and authoritative bodies, and other sources.  In the absence of sufficient information for a given substance, read-across information from structurally similar substances can be used and worst-case exposure assumptions can be made.  Knowledge of potential class effects of other substances with similar chemical composition is useful and should be taken into consideration.  Using all of the acquired information, a safe level of exposure for the substance can be derived based on known or anticipated use patterns for the product in question (daily tablet, weekly injection, implanted device, etc.).  All of these factors combine to generate a scientifically robust and defensible approach that addresses the risks of exposure to potentially hazardous substances and that can help establish specification limits, resolve contamination issues, and improve product quality.

Experts in the Pharmaceutical & Healthcare group at Intertek Scientific & Regulatory Consultancy routinely conduct toxicological risk assessments to address risks associated with exposure to potentially hazardous substances in drugs, biologics, and medical devices intended for use in patients ranging in age from premature neonates to the elderly.  In fact, we have conducted over 200 such assessments in the past few years alone, many of which have been done on extremely tight timelines.  Recent examples include toxicological risk assessments for drug products administered by common routes such as oral, intravenous, dermal, inhalation, and ophthalmic, as well as some that are administered by not-so-common routes such as intrathecal and intralabyrinthine (directly into the inner ear). Not only do our teams of toxicologists perform assessments for drugs and medical devices, they conduct safety assessments on many other products including cosmetics, cosmeceuticals and food additives.

Do you need to proactively identify substances of concern, address an inquiry from a regulatory agency, or deal with a potential product recall because of a contamination issue?  If so, contact us for more information on toxicological risk assessments for drugs, biologics, medical devices, and other healthcare products.

Today’s expert blogger is Valentia Lee-Brotherton. Valentia is Director, Toxicology, with Intertek Scientific & Regulatory Consultancy’s Pharmaceuticals & Healthcare team. She brings more than 15 years of experience in the provision of strategic scientific advice, guidance on toxicology issue resolution, and assistance with regulatory agency interactions.