Extractables and Leachables

Barriers are very important for drug packaging systems. There are two roles demanded of a barrier. The first is to protect drug products from the environment. This is the primary function of a drug container closure system. The second is to prevent drug products from interacting with the packaging materials themselves. Elastomer closure manufacturers have been working to improve these barriers through multiple technologies. The technologies used on commercial products are traditional coating, and film lamination. Each has pros and cons.

Extractables and leachables (E&L) remain as one of the hottest topics in China – a topic to which West makes a strong commitment – in order to anticipate and address ever-changing regulatory and technical requirements. As part of this commitment, Lynn Yao, Scientific Affairs Manager at West, presented Challenges of E&L Study Under Changing Regulatory Environment at the second-annual Extractables and Leachables China, hosted by Smithers Rapra, September 2019 in Shanghai. This event assembled local stakeholders and experts for two days of presentations, training, and discussion on the China regulatory landscape, testing methods, and technical advances.

Since the Technical Guideline on Compatibility Study of Chemicals and Elastomeric Closures was published by the National Medical Products Administration (NMPA, previously known as CFDA) in April 2018, it is essential for pharmaceutical companies to perform compatibility studies. However, for some domestic pharmaceutical companies that lack experience, it is unclear how to perform such a study. To address this, a series of trainings was planned by China National Pharmaceutical Packaging Association (CNPPA) – with the first held in December 2018. There were over 100 attendees from pharmaceutical companies, pharmaceutical packaging companies, NMPA-affiliated labs, and the third-party labs. The training received positive feedback from the participants.

Ophthalmic drug products (ODPs) present a special challenge for the measurement of extractables and leachables (E&L) due to the presence of multiple leachables sources.  ODPs typically are packaged in labelled, semipermeable polymer (e.g., low density polyethylene) containers (i.e., primary container) and stored in cardboard containers (i.e., secondary container) along with instructions for use.  The polymer, label, cardboard and paper are all possible sources of leachables.

In determining extractables from parenteral drug packaging systems, the FDA is clearly looking for appropriate choices of solvents, times, temperatures and other conditions that could impact the results of studies. The outcome of the studies should support the intended purpose – to allow for practical correlations and design of leachables studies.

Understanding extractables and leachables (E&L) is an essential element of determining the suitability of a packaging or delivery system for a drug product.  Recently, PDA presented an interview with Dan Mellon, Ph.D., Pharmacology Toxicology Supervisor at CDER’s Office of New Drugs, discussing FDA’s approach to evaluating E&L information