Regulatory Requirements - FDA Compliance l VR Analytical

Why extractables and leachables testing?

Scientists and engineers who are not familiar with extractables and leachables often ask, "Why the need for testing and analysis?"

cGMP requirements issued by the Food and Drug Administration state: "Equipment shall be constructed so that surfaces that contact components, in process materials, or drug products must not be reactive, additive or absorptive so as to alter the safety, identity, strength or purity of the drug product beyond the offical or otherwise established requirement." (CFR Part 211.65)

This requirement was formerly satisfied by generalized acute toxicity testing such as USP <87> <88> (Biological Reactivity) and non-specific tests such as the measurement of Non-Volatile Residue (NVR) from pure solvent extractions of the test articles. However, these tests could not address non-immediate toxicities such as genotoxicity or carcinogenics, and NVR cannot be performed on many formulations. It also does not capture volatile or semivolatile compounds, which account for much of a typical extraction profile. The Guidance for Industry: Container Closure Systems for Packing Human Drugs and Biologics (FDA 1999) led to formalized testing for extractables and leachables for final container closure systems.

In addition, as the science for detecting and identifying extractables from final containers and closures was developed, it became apparent that not all leachables in final drug products come from the final packaging. Leachables can also come from the processing materials upstream of the final packaging. These materials include the final sterile filter, tubing and connectors; intermediate storage bags and bottles; tangential flow filters; carboys; column resins; and bioreactors. As a result, regulatory and safety concerns have led to increased testing for extractables and leachables upstream of final containers and closures. This allows the industry and regulators to better understand the potential risk to patient safety and/or drug efficacy caused by leachables.

You benefit from VR Analytical's many years of experience conducting tests on a wide variety of manufacturing and packaging materials. This experience makes it possible, often in advance of testing, to know what to expect from your materials. With clear expectations in hand, we can execute customized studies using advanced instrumentation in a cGMP-compliant environment.