Pharmacy Courses

Extractables and Leachables Study in Pharmaceutical Industry

Container Closure System is a protective barrier for the drug product and maintains quality and safety. It must be compatible with the drug product to ensure that there is no negative impact on its efficacy or safety. 


Extractables are substances that can be extracted from a material, component, or system by using a solvent. These are the chemical components present in the packaging material that have the potential to migrate into the drug product. [One time study for Container closure system done by packaging material manufacturer]

Leachables are substances that are present in the drug product due to its contact with the packaging material. [Study to be done on Container closure system + drug product at the end of shelf-life i.e., specific to the drug product and it is done by drug product manufacturer].


The need for E/L studies arose in the late 90s when regulators became increasingly concerned about the adverse effects and fatalities that were suspected to be caused by impurities leaching from the packaging material into the drug product, particularly a concern for Orally Inhaled and Nasal Drug Products (OINDP). 

Study should answer 3 fundamental questions:

 1. What: Identify the potential E&L that could be present in the packaging material. [Analysis of the material composition, manufacturing process, and packaging design].

 2. How: Assess how they interact with the drug product. [Understanding the chemical reactions, adsorption, and permeation processes that may occur].

 3. How much: Determine the potential amount of E&L that could migrate into the drug product and their concentration. [Conduct quantitative analyses to establish safe limits for these substances].


Interpretation of results depends on the route of administration of the drug product and nature of E&L compounds. For parenteral products, the Safety Concern Threshold (SCT) is 1.5 μg/day. For compounds that are not sensitizers or irritants, a leachable exposure of up to 5 μg/day is acceptable. However, for compounds that have general toxicity, the threshold is 150 μg/day, and for orally inhaled and nasal drug products, the SCT is 0.15 μg/day.

The results of an E/L study are then compared with the established safety limits to determine the compatibility of the packaging material with the drug product. 

If the levels of E/L are within the acceptable limits, then the packaging material is deemed safe for use. 

If not, appropriate measures must be taken to mitigate the risk, such as changing the packaging material or implementing additional measures to reduce the migration of these substances.

However, the process of conducting these studies is not without its challenges. Challenges include: 

1. Lack of expertise, 

2. Supply chain complexities, 

3. Timing of the study and 

4. Lack of defined standards.

By addressing these challenges, the pharma industry can ensure the safety and efficacy of drugs and medical devices.

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Resource Person: Bharathi Kodali

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