Chemical characterization is an important process in assessing the safety of both medical devices as well as biopharmaceutical container closure systems, packaging products, and delivery systems. During the manufacturing of the aforementioned medical devices and biopharmaceutical container, packaging, and delivery systems, many of the materials used in this process have the potential to cause health problems in humans if not adequately tested for their extractable and leachable properties.

Pacific BioLabs, an ISO 17025 accredited facility with over 40 years experience, provides comprehensive turnkey analytical services for testing extractable and leachable compounds, ensuring that your medical device or biopharmaceutical products are both safe and regulatory compliant.

Click for more Information on Pacific BioLabs’ Medical Device Chemical Characterization.

Testing for Extractables and Leachables from Container Closure, Packaging, and Delivery Systems

FDA defines extractables as “organic and inorganic chemical species that can be released from the surfaces of components used in the manufacture and storage of drug products under laboratory conditions (accelerated or exaggerated temperatures, solvents, or surface exposure)”, whereas leachables are defined as “organic and inorganic chemical species that can be released from the surfaces of components used in the manufacture and storage of drug products under conditions of normal use”. Packaging systems, also referred to as container closure systems, may include primary, secondary, and tertiary packaging components.

Sources of extractables include manufacturing equipment, packaging components, as well as labels, adhesives and inks, whereas sources of leachables can be stabilizers, antioxidants, coatings, emulsifiers, vulcanizing agents, lubricants, dyes, and colorants. Pharmaceutical packaging, device packaging, container closure systems, drug delivery systems, and implantable medical devices can be complex combinations of polymer, rubber, glass, and other materials which can contribute to the E&L profile of the product.

Leachable impurities can migrate from components in container closure systems, packaging systems, storage systems, process equipment and device packaging, that can affect the overall purity and safety of the therapeutic product. In order to identify potential sources of leachables, it is important to conduct controlled extraction studies to identify extractables and the components that generate them.

Therefore, extractables and leachables (E&L) testing is crucial to drug product development, especially for parenteral drug products (injectables like intravenous, subcutaneous, intramuscular), ophthalmic, and orally and inhaled nasal (OINDP) drug products.

With comprehensive analytical techniques, Pacific BioLabs provides the following E&L services following USP regulations:

  • USP <1663> Extractables with pharmaceutical packaging/delivery systems
  • USP <1664> Drug product leachables with pharmaceutical packaging/delivery systems
  • USP <1664.1> Orally inhaled and nasal drug products
  • USP <661> Plastic packaging system and materials (requirement applied before 661.1 and 661.2 becomes official Dec 1, 2025)

Pacific BioLabs’ Services for E&L per USP <1663> and USP <1664>

The analytical chemistry team at Pacific BioLabs can perform comprehensive E&L testing under the following guidelines:

  • Good Manufacturing Practices (GMP)
  • USP Chapters <1663>, <1664> and <1664.1>
  • FDA Guidelines (if required)

Our team can also provide the following requested services:

  • Exhaustive or controlled extractions
  • Simulated leachable studies
  • Customized protocol development
  • GMP testing for E&L and stability studies

In addition to extractables and simulation leachables studies, Pacific BioLabs also provides leachable stability studies to support your (example shown below).

Example Conditions/Schedule for Leachable Study on Registration Batches

CONDITIONS (Temperature/Relative Humidity)TIME POINTS (Months)
25 ± 2°C/60 ± 5%RH3, 6, 12, 18, 24, 36 (to the end of shelf life)
30 ± 2°C/65 ± 5%RH3, 6, 12, 18, 24, 36 (to the end of shelf life)
40 ± 2°C/75 ± 5%RH3 and 6

Our dedicated expert team will work with the client to design a study that best meets the client’s needs and goals for regulatory as well as product development purposes.


Analytical Techniques available at Pacific BioLabs

Testing per USP <661>

Systems used to package therapeutics products – often called “Packaging Systems” – are generally constructed and composed from materials that may include glass, metals, plastics and elastomers/homologous polymers with a range of molecular weights and several additives. These systems are usually in contact with the pharmaceutical product at some point during manufacturing, storage or administration and cause a big concern regarding safety. With recent revisions, the USP <661> focuses on Safe Plastic Packaging for Pharmaceutical Products.

New packaging systems that have not gained regulatory approval for use with a to-be-marketed pharmaceutical product would need to be tested according to <661.1> and <661.2>. Pacific BioLabs offers testing services catering to both USP <661.1> and <661.2> chapters. Our objective is to help you determine the required testing for your materials and the ideal testing matrix so you will be able to plan ahead for your product.

USP <661.1> Plastic Materials of Construction

The purpose of USP chapter <661.1> is to determine whether a material has been well-characterized for its intended use and is designed to ensure that the material characteristics match the relevant performance requirements.

This chapter solely applies to individual plastic and raw materials, and contains tests, methods and specifications for cyclic olefins, polyethylene, polypropylene, polyethylene terephthalate, polyethylene terephthalate G, and plasticized polyvinyl chloride.
This testing for identification, characterization, and general physiochemical properties includes the following:

USP <661.2> Plastic Packaging Systems for Pharmaceutical Use

USP chapter <661.2> provides test methods and standards for plastic packaging systems such as bags, bottles, blister packs, inhalers, syringes and vials. The testing matrix would primarily depend on the composition of the packaging system. For <661.2> the focus is on suitability for use with respect to patient safety, and therefore the following testing regimen would be inclusive of the establishment of the packaging systems:

Why Partner With Pacific Biolabs For E&L Testing?

  • Highly trained and experienced scientific staff, dedicated to providing the highest quality results under the strictest deadlines
  • Extensive suite of the most state-of-the-art analytical instrumentation, including TOF-MS (allowing high resolution/accurate mass), GC, GC-MS, ICP-MS, HPLC, and LC-MS/MS
  • Courteous, attentive, and helpful support staff to ensure effective study planning and execution
  • Over 40 years’ experience and a proven track record of -of helping our partners achieve their E&L testing and product development goals

Read More About Plastic Package Testing

Pacific BioLabs