Pharmaceutical - Extractables & Leachables

The examination of extractables & leachables from the primary packaging of drug delivery devices is growing in importance. This increased focus has arisen from various guidelines produced by the FDA - e.g. Guidance for Industry - Nasal Spray & Inhalation Solution, Suspension, & Spray Drug Products – CMC (2002) & Guidance for Industry - Metered Dose Inhaler & Dry Powder Inhaler Drug Products – CMC (1998). Such guidelines indicate that an assessment of the safety & compatibility of packaging & closures should be conducted during the early stages of a new drug or formulation.

The FDA guidelines are concerned with various drug delivery devices, including meter dose inhalers (MDI) & dry powder inhalers (DPI), & cover a wide range of aspects including Extractables & leachables from the rubber & plastic components of the Primary Packaging.

The assessment criteria vary depending upon the route of administration, with pulmonary & injectable drugs having the strictest requirements. Guidance is available from:

• The Food & Drug Administration Website (CPMP)
  http://www.fda.gov/cder/guidance
• The European Agency for the evaluation of Medical Products (EMEA)
  http://www.emea.europa.eu
• Product specific guidance on Metered Dose Inhalers & Dry Powder Inhalers can be found at
  http://www.fda.gov/cder/guidance/2180dft.pdf

In recent years the PQRI Leachables & Extractables Working Group has published best practice guidelines for Extractables & Leachables Testing - Safety Thresholds & best practices for Extractables & Leachables in Orally Inhaled & Nasal Drug Products (2006). These guidelines have made an important contribution to Extractables & Leachables Testing of Orally Inhaled & Nasal Drug Products (OINDP). They provide a framework for assessing the potential for substances that may possible migrate from the primary packaging or other containers into dosage forms, to affect those drug products. The contamination effects could include increasing the impurity levels in the metered drug, increasing the toxicity of a drug, be a cause of precipitation or alter the drugs pH value.

Our Consultant team at Smithers Rapra is experienced in conducting the three main stages of the assessment of Extractables & Leachables in OINDP, as recommended by the PQRI:

• Extractables
• Leachables
• Routine Extraction Testing