Over the years, the US Pharmacopeia (USP), International Harmonisation (ICH), Product Quality Research Institute (PQRI), and several other industry consortia have developed guidelines and best practices for these extractables & leachables studies.

Alcami has specialized knowledge of the most common materials of construction such as platinum-cured silicon, halobutyl rubber, cyclic olefins, polyethylene terephthalate (PET), polyvinyl chloride (PVC), and other elastomers. Vial and stopper configurations, spray pumps, and intravenous (IV) bags are among the most common packaging system components we evaluate. We welcome all routes of administration, including the more challenging prefilled syringes, blow-fill sealed vials, and laminated cans.

Alcami recently authored an article featured in Drug Development & Delivery titled "A Practical Approach to Extractables & Leachables." 

INTRODUCTION

The study of extractables and leachables (E&L) has been evolving for many years. As pharmaceutical manufacturers, packaging vendors, and regulatory agencies gain more knowledge of extractable compounds, the scope of E&L guidelines grows with it. Many of the case studies that initiated interest in extractables and leachables are based on primary packaging. In some cases, the secondary or tertiary packaging were identified as sources of leachables. As a result, the primary emphasis of extractables screens has been on the packaging systems. The approach to these screens is well established. The first iterations of regulatory guidance addressed the common packaging materials in the United States Pharmacopeia (USP) chapter <661>, which relied heavily on physiochemical testing to characterize the material of construction but did not directly address extractables testing of the final packaging materials in detail. With advancements in the manufacture of plastics and increasing variety of base polymers used for packaging systems, it became evident that more specific guidelines are needed.

Agency expectations are quickly evolving for the evaluation of drug product packaging and delivery systems and the surfaces used during manufacture with respect to potential leachables. Every new and generic drug product must be assessed for extractables and leachables (E&L). In this top five list, Alcami experts will address the extractables and leachables questions our experts hear most.

1. What is the difference between an extractable and a leachable?
   Extractables are compounds that can be extracted from a packaging component, delivery system, or manufacturing surface via laboratory manipulation, such as exposure to solvents or heat. Extractables can be potential leachables. Leachables are compounds that passively migrate into the drug product over time, as a result of direct contact from the packaging system, in-use componentry, or a manufacturing surface.
   
   

Requirements from regulatory agencies have become increasingly rigorous with regards to the detection, identification, and quantitation of extractable and leachable compounds in pharmaceuticals, drug delivery systems, and biomedical devices. This heightened scrutiny is the result of several well‐documented incidents of contaminants leaching from containers and packaging, causing potential or real risk to humans. Therefore, regulatory agencies, such as the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA), have increased regulations on potential extractables and leachables in drug product container and closure systems.

The study of extractables and leachables is among the fastest-evolving disciplines in the pharmaceutical industry. Until recently, the primary focus of these studies has been components in direct contact with the drug product for extended periods, such as the primary packaging, or those that contact the formulation during administration, known as in-use componentry. However, the components used in manufacturing are of increasing interest as sources of potential leachables. Many components are single-use systems (SUS), polymeric in construction, and pre-treated prior to use. Each of these factors increase the potential for leachable compounds. In order to evaluate materials for potential leachable compounds, one must leverage a scientifically rigorous study design against the specific potential for drug product and packaging/surface interaction. 

Regulatory agencies have become increasingly rigorous with regards to the detection, identification and quantification of extractable and leachable compounds in pharmaceuticals, drug delivery systems and biomedical devices. This increased scrutiny is the result of several well-documented incidents of contaminants leaching from containers and packaging, resulting in a potential or real risk to humans. 

Alcami has recently authored a white paper on extractables and leachables testing in the pharmaceutical industry.