Not all plastics are created equal. Plastic and polymeric products, parts and components can include significant numbers of chemical constituents—so it is important to understand how a filter, bag, container, delivery system or implantable device will react while in use. Complete chemical characterization is necessary to determine what compounds are present and how these compounds may impact patients.
Many chemicals present in plastic and polymer products are expected, but some are unexpected—and potentially harmful. Extractables/leachables (E/L) testing is the most effective way to identify and quantify all compounds within a delivery system, container or other test article. E/L testing comprises two kinds of testing to identify chemical constituents in a medical device.
- Extractables testing: Generates “worst-case” data and ascertains how plastics and polymers react to exaggerated conditions (range of solvent polarities, high temperatures, extended time frames, etc.).
- Leachables or Simulated-Use Extractables testing: Assesses what chemical compounds may migrate from a plastic or polymer during “normal” or clinically relevant conditions. Often, testing deemed “clinically relevant” is simulated due to the challenges of working with actual biological matrices.
Even common materials or those with a long history of clinical use can contain chemicals of concern—and regulatory bodies are taking notice. Per ISO 10993-1, most medical devices require extractables studies and a toxicological risk assessment, with potentially additional chemistry (e.g., leachables or simulated-use extractables) to mitigate risks and address biocompatibility endpoints.
Caution is Key
Polypropylene has been approved by the U.S. FDA for use in more than 170 health care products—sutures, surgical mesh, cardiovascular patches, packaging and single-use systems, to name a few—but the material is not implicitly safe in all use cases. Analytical chemist Dennis Jenke identified 35 extractables associated with polypropylene materials, some of which can present a toxicological concern even at very low levels. Take benzopyrene, for instance: Though frequently used in polypropylene production, benzopyrene can cause cell mutations and lead to various forms of cancer in addition to developmental toxicity.
Clinical use case also matters. Recently, the U.S. FDA identified a potential risk of exposure to toxic chemicals associated with silicone tubing in three models of a major manufacturers’ hemodialysis machines, all of which were introduced in 2008. Two of the models are no longer manufactured but remain in clinical use. Given the role these machines play in purifying patients’ blood, any level of toxicity could pose significant safety risks.
Comprehensive E/L studies can identify and help mitigate risks before potentially harmful chemical compounds impact patient safety. To do so, manufacturers need to embrace testing as a journey of discovery rather than a one-and-done affair.
Vet Your Lab Testing Partner
Not every laboratory testing partner is capable of complete chemical characterization with no unknowns, and the level of vigor in E/L testing can vary. Ask the right questions early in the process to prevent surprises down the road. Helpful questions include:
- How long has the laboratory been conducting E/L studies? How many programs have you run?
- Can you commit to the elucidation and complete identification of all components?
- Is complete identification included in price and timeline quotes, or does this incur an additional charge? What is your on-time delivery record and when does that clock start?
- What support do you provide after analytical testing concludes? Is the testing team available to address regulator questions?
Some laboratories may claim to offer E/L testing but fail to deliver complete chemical characterization when the process becomes complex or time consuming. Asking the right questions when vetting partners allows manufacturers to make informed decisions, streamline the testing process and market safe products.
A Final Word on E/L Testing Just because a plastic or polymer has been used before does not mean that manufacturers can assume it safe for a specific application or use case. Complete E/L testing identifies all chemicals present within a product. When unknowns are present, it is virtually impossible for the toxicologist to assess the device’s toxicological risk accurately; and unidentified chemicals must be considered carcinogenic or genotoxic. Savvy manufacturers will question every unknown compound related to their container, delivery system, or product—because they know regulators will flag them. Lab testing partners who fail to identify all compounds or attempt to proceed with unknowns present should be equally scrutinized.