Tag Archives: extractables and leachables

Some Background and Concerns About PFAS

PFAS

The Background and Concerns of PFAS

PFSA structure(Per- and) PolyFluoroAlkyl Substances (PFAS) are a class of ubiquitous chemicals that have been found in water, air, fish, and soil across the nation and worldwide. Known as “Forever Chemicals,” there are thousands of different PFAS, and they are present in consumer, commercial, and industrial products.1 Having one of the strongest bonds in organic chemistry, their structures proved to be resistant to heat, water, oil, and degradation.2 They are found in “food packaging and non-stick cookware, cosmetics, waterproof and stain-proof textiles and carpet, aqueous film forming foam (AFFF) to fight Class B fires, and as part of metal plating processes.”3 Teflon and Scotchgard were two of the pioneering products to utilize these fluoropolymers. The two most common PFAS are perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS).

Health Concerns of PFAS

Some of the most frequently cited health concerns associated with PFAS include adverse cardiovascular, immunity, developmental, and hepatic effects.3,4The most commonly heard refrain to minimize these concerns is that if they are so prevalent, why are there
not more health issues associated with them? In fact, “The Lancet Commission on Pollution and Health reported that pollution was responsible for 9 million premature deaths in 2015, making it the world’s largest environmental risk factor for disease and
premature death.” This was updated in 2019, and those numbers held steady, accounting for one in six deaths worldwide.5/i> While this number includes all types of pollution, the impacts are clear.

The Exposure Concerns of PFAS Are Regulatory and Legal

Due to their combination of persistence, pervasiveness, mobility, and the ability of some to bioaccumulate (or build up in animals and humans), they have been in the news recently too.6 Predictably, they are also now moving through the courts.7-9 Some of the most common areas of litigation are directed at PFAS found in drinking water and firefighting foam. The regulatory initiatives are also increasing. These address a range from water and soil to numerous manmade products including food packaging.10,11 The European Chemicals Agency (ECHA) and the NIH have a wealth of guidance and regulations that apply to PFAS.12,13

PFAS Detection

The EPA has useful direction for analytical methods development and sampling research that outlines the “laboratory validation process following a particular rulemaking or guidance effort and are available to support regulatory or guidance activities.”14 For
technique and equipment, PFAS are typically analyzed by mass spectrometry, coupled with gas chromatography or liquid chromatography (GCMS and LCMS), which enables detection in the low parts per billion.

AMPAC Analytical has years of experience and numerous experts in trace analysis by mass spectrometry who can assist with method development for high-volume analyses for both common and atypical sample matrices that will allow you to stay ahead of evolving regulatory concerns. Please contact us with specific questions or to receive a quote for PFAS quantitation.

References

  1. PFAS Explained | US EPA
  2. Understanding Organofluorine Chemistry. An Introduction to the C–F bond – Chemical Society Reviews (RSC Publishing)
  3. PFAS Health Effects Database: Protocol for a Systematic Evidence Map – ScienceDirect
  4. Toxicological Profile for Perfluoroalkyls (cdc.gov)
  5. Pollution and Health: a Progress Update – The Lancet Planetary Health
  6. ‘Forever Chemicals’ Are Everywhere. What Are They Doing to Us? – The New York Times (nytimes.com)
  7. PFAS Settlements: Future of PFAS Litigation Landscape to be Determined by Upcoming Decision | Reuters
  8. PFAS: The New Frontier of Product Liability – ProQuest
  9. DuPont, Corteva, and Chemours Announce Resolution of Legacy PFAS Claims | DuPont
  10. Trends in the Regulation of Per- and Polyfluoroalkyl Substances (PFAS): A Scoping Review
  11. PFAS in Food Packaging: State-by-State Regulations – September 2023 | Bryan Cave Leighton Paisner – JDSupra
  12. Per- and Polyfluoroalkyl Substances (PFAS) – ECHA (europa.eu)
  13. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up – NCBI Bookshelf (nih.gov)
  14. PFAS Analytical Methods Development and Sampling Research | US EPA

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Extractables and Leachables

blank pharmaceutical and drug packaging

Extractables and Leachables (E&L) are essential areas of concern for the pharmaceutical and food industries, specifically regarding their packaging, usage components (e.g., medical devices or syringes), and the manufacturing chain. We will examine testing of analysis of them within pharmaceutical applications. The two terms are related but distinct, each with its own analytical requirements.   

Definitions of Extractables and Leachables 

A handy article published in Pharmaceutical Engineering by the International Society for Pharmaceutical Engineering (ISPE) explains that “Extractables are chemical compounds that migrate from single-use systems (SUS) into model solvent solutions under controlled and exaggerated conditions depending on temperature, pH, polarity, and time.” In other words, this happens when using strong solvents. They note that “SUS are normally not exposed to such conditions in biopharmaceutical processes.”1  

ISPE’s article defines leachables as “chemical compounds that migrate from SUS into process solutions under normal biopharmaceutical process conditions. They further clarify that these compounds “may end up in the final drug product formulation. For the most part, leachables are a subset of extractables, although interaction with product components may produce leachables not seen as extractables.”1 

Guidance on Extractables and Leachables 

The FDA has released a series of guidelines for the pharmaceutical industry, including Container Closure Systems for Packaging Human Drugs and Biologics, that provide guidance for submission in support of an original application for any drug product. It also covers a wide range of forms and delivery systems of drugs:

  • Inhaled 
  • Injected 
  • Liquid-based  
  • Oral  
  • Solid oral dosage forms  
  • Ophthalmic 
  • Topical and topical delivery systems  
  • Powders for reconstitution   
  • And other dosage forms 

Additionally, the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) also has issued the ICH Q3E: Guideline for Extractables and Leachables.2,3 These are both useful in providing direction for E&L concerns and control strategies. 

Plan Against Extractables and Leachables 

To guarantee adherence to all guidelines and regulations while ensuring patient safety, it is crucial to know and utilize materials compatible with your product. To accomplish this, solvent use, packaging, and delivery systems must all be tested and analyzed in cGMP and FDA-compliant laboratories.  This should include the following:

  • A thorough review of all materials used in packaging and production, production, and equipment to predict the compatibility of your packaging system with your product. AAL can provide reports for items from each step. 
  • Extraction studies on the materials used. 
  • Leachable studies to identify any impurity resulting from those materials found in the final product under normal usage conditions. 
  • If impurities are detected, AAL can provide toxicological evaluations, including profiles of the impurities and the risks they pose for the patients, establish safety limits, or adjust for different forms of medication application. 
  • We can assess risks created by various exposure levels due to the impurity in the finished product. 
  • Finally, AAL provides a detailed report of our findings in accordance with the applicable governing bodies (e.g., FDA, EMA, PQRI, PDA). 

 AMPAC Analytical can review your analysis and testing needs for extractables and leachables for any forms and delivery systems listed in the table above, complying with the strictest standards necessary. 

References 

  1. https://ispe.org/pharmaceutical-engineering/may-june-2017/extractables-leachables-not-same 
  2. https://www.fda.gov/media/70788/download 
  3. https://database.ich.org/sites/default/files/ICH_Q3E_ConceptPaper_2020_0710.pdf 

Resources