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The Growing Need for Extractables & Leachables (E&L) Testing of Biopharmaceutical Manufacturing Equipment

As part of the drug approval process for the U.S. Food and Drug Administration (FDA), all drugs in development must undergo extractables & leachables (E&L) testing. In the past, the FDA emphasized oversight of E&L testing for drugs that came with both a high-risk route of administration and high risk of packaging and dosage form, such as inhalers and injectables.

More recently, the FDA has widened its focus to include E&L testing oversight on other products, such as topical solutions and tablets, and significantly expanded to include the testing of disposable manufacturing components most frequently involved in biologic drug production.

The FDA’s Role in E&L Oversight

The FDA approves drug products, and extractables and leachables (E&L) testing is part of the expectation for a drug submission. However, the FDA guidance on E&L testing is generally not prescriptive and is open to interpretation as to its implementation.

This can mean that a manufacturer may produce a drug according to generally accepted industry standards, unaware that the FDA’s interpretation of its regulations has become stricter. As a result, the company will receive a finding from the FDA that its E&L testing no longer meets the FDA’s expectations. These unexpected steps can increase costs, delay drug development, and lengthen time-to-market.

Increased Surveillance of Pharmaceutical Manufacturing

A few years ago, you would never have thought that the FDA would be worried about the tubing that a drug product travels through, or a stainless-steel holding tank, as material contact is so transient. This has changed as the FDA has evolved to make sure there is no risk to public health.

While manufacturing equipment wasn’t even on the FDA’s radar 20 years ago, several incidents may have drawn their attention. In 2011, Ortho-McNeil-Janssen Pharmaceuticals, Inc. recalled 40,000 bottles of pills that had been contaminated by a chemical residue on wooden pallets during manufacturing. While there may be a low risk for E&L in manufacturing equipment, the trend appears to be that the FDA now expects these components undergo testing during the drug manufacturing process.

CROs Can Help Companies Navigate the E&L Process

The FDA’s changing expectations means that companies are more likely to get a finding from the FDA if they do not perform E&L studies on manufacturing components. Repercussions, such as time lost and additional csts, can be significant. Many companies are not capable of performing this kind of testing independently because it requires the analytical expertise in polymer science and additives. One cost-effective option is to outsource to a CRO.

How is Avomeen Addressing These Changes in our Lab?

While many CROs offer E&L testing services, Avomeen is specially equipped to handle these because we do not hire exclusively from a traditional pharmaceutical background. This gives us the knowledge needed to perform E&L testing of manufacturing equipment. We also offer:

  • An elemental analysis unit to conduct metals testing
  • A database containing 300-400 distinct plastic additives
  • Expertise in polymers, plastics and rubbers

Our expertise and extensive resources help us address increased expectations from the FDA by rapidly identifying a greater range of contaminants.

To hear more about what Andrew Kolbert, PhD, MTM, President and Chief Technical Officer at Avomeen has to say about E&L testing, check out his interview in Contact Pharma.

Additional Resources

Learn about our proprietary plastic additive database in our blog, Best-In-Class Polymer Additive Library for Identification of Extractables.

Looking for more information about our proprietary polymer additives database? Check out our Development of a Library of Plastic Additives for Identification of Extractables Poster Presentation.

Looking for a summary of USP guidelines for E&L testing? Our blog, The Long and Short of USP Guidelines for E&L Testing, offers some guidance.

The FDA Gets Stricter with E&L Oversight, Can the Industry Keep Up? article in Contract Pharma, featuring Dr. Andrew Kolbert, Avomeen’s CTO, offers valuable insight.

In our years supporting the biopharma industry, we’ve seen some common mistakes made in E&L study design. We’ve outlined what not to do in our blog, Common Pitfalls in Ectractables & Leachables Testing.

Learn more about FDA’s increasing oversight of E&L testing in pharma in Dr. Kolbert’s article in Tablets & Capsules Magazine.