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Trinity Validates Patch Safety Through Extractables & Leachables Testing

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Pharmaceutical Leader Evaluates Safety and Quality of New Transdermal Patch

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Life SciencesLife Sciences

Industry

Pharma Manufacturing

Location

United States

A global pharmaceutical leader is committed to providing medicines and therapies that improve outcomes for people with a wide range of health conditions. One of its products, a transdermal patch, is critically important not only to the health of the patients who use it but also to the company’s bottom line, so when the company learned that one of its suppliers had changed the formulation of one of the components, leaders knew they needed to take action. The company engaged SafeBridge, part of Trinity Consultants, to assess potential risks to product safety and quality and ensure regulatory compliance.

Challenge

The U.S. Food and Drug Administration (FDA) typically requires comprehensive evaluations of extractables and leachables (E&L) as part of the approval process for new or existing pharmaceutical products, including transdermal patches. In addition to being an important part of the regulatory evaluation process for new products, E&L testing is also required when there is a change in the packaging of an existing product, such as a change in any packaging that directly or indirectly comes into contact with the drug. This evaluation includes conducting studies to identify and quantify the leachables and assess the potential toxicity of substances that may migrate from the patch components into the drug formulation or the patient’s skin. The testing and evaluation process, however, is highly complex and can feel a bit like the Wild West—there’s limited guidance and a lack of standardized methods, leading to variability in testing protocols and analytical techniques. The pharmaceutical leader turned to SafeBridge to design, perform, and analyze the results of E&L testing.

Solutions

The SafeBridge team began by finding a laboratory to perform the testing, then designed and reviewed the analytical protocol that would be used. SafeBridge then performed an extractables study to mimic the characteristics of the product under investigation as well as a simulated leachables study using artificial sweat as the extractable solvent.

Then, the team analyzed the results of the E&L testing. During this process, SafeBridge calculated the “Worst Case Patient Exposure” using the maximum daily dose (MDD) and performed a toxicological assessment on compounds above the Analytical Evaluation Threshold (AET) using a Threshold-of Toxicological-Concern (TTC). SafeBridge also performed a health-based risk assessment by calculating Permitted Daily Exposure (PDE) values for each compound and applying adjustment factors to the Point of Departure (PoD), which is a critical step in using toxicological data to establish a safe exposure level for leachable compounds. When data was not available for the specific chemical, the team conducted a literature search to adjust the Point of Departure (PoD), including looking at analogous compounds, and leveraged in silico modeling to evaluate genotoxicity potential. After calculating the PDEs, SafeBridge compared them to the worst-case patient exposure to determine the acceptable Margin of Safety for patient exposure.

Services Performed

The team designed a full extractables and leachables testing plan, oversaw extractables and simulated leachables studies, and calculated worst-case patient exposure (MDD). They applied TTC, determined PDE values, researched analogs, and modeled genotoxicity, delivering a defensible toxicological report for FDA review.

Results

Throughout the process, the SafeBridge team leveraged its extensive experience and expertise in chemistry, toxicology, and project management to ensure that the testing and analysis avoided common pitfalls and delivered the scientific rigor needed to support its findings—and delivered those findings in a report designed to facilitate a smooth review by the FDA and avoid numerous follow-up questions that could delay approval.

As a result, the pharmaceutical leader was able to efficiently meet the first significant milestone in releasing a transdermal patch using the new formulation, speeding regulatory approval and helping ensure that patients will have timely access to the medication they need.

1

Complete E&L programs

100%

Safety Margin

Zero

FDA delays