BPOG Extractables and Leachables

Are your BPOG protocols up to date?

What is a BPOG protocol?

The BioPhorum Operations Group (BPOG) is a collection of companies encompassing approximately 80% of the global commercial biopharmaceutical capacity. Collectively, in 2014, they published “Best Practices Guide for Evaluating Leachables Risk from Polymeric Single-Use Systems Used in Biopharmaceutical Manufacturing” and “Standardized Extractables Testing Protocol for Single-Use Systems in Biomanufacturing.”

BPOG Extractables and Leachables

These documents have been widely recognized across the biopharmaceutical and biopharmaceutical supply industries as a “one stop shop” for extractables and leachables testing principles and best practices, though the FDA does not formally recognize either BPOG document as a standard for assessment (you can read more about this on our BPOG page). The relevant USP chapter is <USP 665> Polymeric Components and Systems Used in the Manufacturing of Pharmaceutical and Biopharmaceutical Drug Products.

The importance of SUS extractable studies

Smaller batch sizes and ambient processing conditions have led to a rapid increase in single-use systems (SUS) and SUS components in biopharmaceutical manufacturing. These systems often improve cost effectiveness, operating efficiency, and the environmental sustainability of processes. However, as many of these components are polymeric (plastic), there is growing concern about leachables in the manufacturing process. In order to identify and target potential leachables, extractables and leachables (E&L) studies are performed.

SUS suppliers need the data from these studies in order to ensure the safety of their products. Biopharmaceutical end-users need SUS extractables testing data and leachable evaluations to assess the fitness of a given SUS component for their manufacturing processes and in preparing risk assessments for submission to regulatory agencies.

Examples of SUS components that come into contact with product or process fluids include:

  • Tubing and connectors
  • Tank liners and mixing bags
  • Sensors
  • Valves
  • Elastomeric parts
  • Filters and chromatography columns
The BPOG Update

Since publishing the 2014 standardized extractables protocol, BPOG has been collecting the now directly comparable extractable data generated per the protocol from over 90 manufacturers and suppliers. After five years of data review, BPOG determined that they had both acquired enough BioPhorum partners and obtained enough data through these partners to determine what extractable testing was necessary and sufficient for the industry. In April 2020, BPOG released an update to their extractables protocol titled “BioPhorum Best Practices Guide for Extractables Testing of Polymeric Single-Use Components Used in Biopharmaceutical Manufacturing”. This document revises the initial protocol according to the data and feedback received since 2014.

What information will I find in the April 2020 revision?
  • Four recommended extraction solvents to represent a variety of conditions: water for injection (WFI) or deionized (DI) water, low pH (0.1M phosphoric acid), high pH (0.5N NaOH), and 50% ethanol
  • A recommended sample surface area to extraction solvent volume ratio of 6 cm2/mL or higher
  • Consideration for extraction controls
  • Specific guidance for handling solvent evaporation loss (which is sometimes unavoidable)
  • A consistently proposed extraction temperature of 40°C
  • Component-dependent exposure times (24 hours, 7 days, 21 days, and/or 70 days)
  • A helpful table of specific considerations for extraction by potential sample type
  • Recommended approaches for the four major established analytical techniques (including instrument parameters and specifications to be met)
    • LCMS: high pressure/performance liquid chromatography coupled with mass spectrometry
    • GCMS: gas chromatography with mass spectrometry, direct injection
    • GCMS: gas chromatography with mass spectrometry, headspace
    • ICP-MS: inductively-coupled plasma mass spectrometry
  • Guidance for standard selection and quantitation methods
  • Reporting recommendations
What major changes have been made since the first BPOG protocol?
  • Clarifications about the purposes and application of the protocol
  • A reduction in the number of recommended extraction solvents (5M sodium chloride and 1% polysorbate 80 solvents were shown to have low unique extraction capability)
  • No elemental analysis of 50% ethanol extracts is recommended (again due to low unique extraction capability but also due to instrumental limitations)
  • Removal of assessment of “time point zero” extracts
  • Additional detail on standard preparation and instrumental qualification (including specifications)

EKG has written more extensively on BPOG, the relationship of the BPOG protocol(s) to regulatory standards, and other practical considerations related to BPOG. To view our entire reflection, please click here.

Extractables and Leachables Studies at EKG Labs

Understanding the complex chemical interactions between pharmaceuticals and materials is critical to designing a proper extractables and leachables program. We can perform E&L analytical studies with the ultimate goal of submitting data for FDA review and approval. EKG Labs is familiar with guidance from BPOG as well as from organizations such as ISO, ICH, and USP. Our capabilities include:

To find out more about our BPOG and E&L programs, contact EKG Labs at info@ekglabs.com, at 810-354-5229, or via our website.

About EKG Labs

EKG Labs is an analytical service provider for the pharmaceutical and medical device industries. Our wide variety of analytical services support product development, regulatory filings, and analytical chemistry investigations.