Extractables and Leachables

VIMTA is the No.1 choice in India and a specialist in analytical services, supporting the pharmaceutical, biopharmaceutical and animal health industry. Our analytical services support the entire life cycle from early phase drug development, to regulatory submissions and GMP manufacturing, to post marketing analytical testing requirements.

Potential interactions between drug product and its

  • container closure systems and
  • manufacturing process contact material

are an important regulatory consideration for Pharmaceutical and Biopharmaceutical companies. Each drug application (human drug or biologic) filing should contain enough information to show each proposed container closure system and safe and suitable for its intended use. The type and extent of information that should be provided in an application will depend on the dosage form and the route of administration.

As per cGMP regulatory requirements (21 CFR Part 211.94 (a)), drug product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality or purity beyond the official or established requirements, and therefore drug product should be evaluated for any chemical contaminants or impurities that maybe generated during manufacturing or storage. This evaluation is performed by extractable and leachables studies.

Extractables are any chemical species that can be removed from a packaging component or device or manufacturing process contact material, into solvents under controlled laboratory conditions (e.g., component is cut in pieces and incubated with solvent). Leachable is an extractable that actually migrates into a drug product under storage conditions. Not all extractables are leachables and neither are all leachables correlatable to extractables.

Container Closure System refers to the sum of the packaging components that together contain and protect the dosage form. This includes both primary and secondary packaging components.

VIMTA can provide customized protocol driven extractables and leachables testing services to help you ensure that your product meets applicable regulations requirements and is safe for the patient. Our scientific team, with experience of over 200 E & L studies under its belt, is well versed with the science, regulations, guidances and standards related to E&L studies. Our data has been submitted to, and well accepted by, US and European regulatory authorities.

Applicable Guidelines and Regulatory Requirements

  • USP<1663> Assessment of Extractables Associated with Pharmaceutical Packaging / Delivery Systems
  • USP<1664> Assessment of Drug Product Leachables Associated with Pharmaceutical
  • PQRI (March 2007) Guidelines for Reporting and Qualification Thresholds for Leachables in Parenteral and Ophthalmic Drug Products
  • PQRI (Sept 2006) – Guide Safety Thresholds and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products
  • USFDA Guidance for Industry (1999) on Container Closure Systems for Packaging Human Drugs and Biologics
  • USFDA Guidance for Industry (2002) on Nasal Spray and Inhalation Solution, Suspension and Drug Products Points of Consideration
  • USFDA – 21 CFR 600.11] – Biological products – (b) Equipment – (h) Containers & Closures
  • EMA – CPMP / QWP /4359/03 – 2005 – European Medicines Agency – Guideline on plastic immediate packaging materials
  • ICH Q3A/B (R2) – 2006 – Impurities in New Drug Substances/Products.
Study Approach

Extractable Testing

  • Packaging material assessment and development of customized study protocol
  • Controlled extraction utilizing PQRI protocols (with minimum 3 solvents)
  • Qualitative and quantitative analysis of extractables using HPLC, LC-MS / MS, GC-MS / MS, ICP-MS, IC etc
  • Identification of unknown compounds
  • Method development, optimization and validation of controlled extractable study for routine control of container closure system
Leachable Testing

  • Method development and validation for quantification of specific leachables in the drug product
  • Identification & quantification of all compounds not found in control product
  • Leachables monitoring in stability study samples
  • If end of shelf life samples are not available, we can take up ICH stability testing to generate the leachables
  • Correlation establishment of potential leachables and actual leachables
  • Evaluations of results for toxicology issues - A toxicological evaluation should be made of the extractables and leachables from the container closure system. The assessment should include appropriate In Vitro and In Vivo tests. Alternatively, we can also support with applicable citations and additional safety data
E & L Analysis and Allied Services

  • Label Migration Studies (Gum and link migration studies)
  • Delamination Studies (Glass Vials, Syringes etc.)
  • Packaging Safety & Toxicity Analysis (In-house GLP certified, AAALAC accredited preclinical study capabilities)
  • Controlled Extraction Studies for Raw Material Control
  • Stability Studies
  • Genotoxic Impurity Studies
  • Physical Characterization Testing
Products Experience

  • Inhalations
  • Opthalmics
  • Parenterals, injectables
  • Oral vaccines
  • Topicals
  • Dermal Pathches
  • Implants
  • Solid dosage forms
Packaging Material Experience

  • Rubber stoppers
  • EPDM packaging
  • Gaskets & O-rings
  • Inhalation devices
  • Prefilled syringes
  • Implants
  • Glass vials
  • Syringes
  • Resins
  • Injectable bags / vials
  • Films, blister packs
  • Laminated tubes
  • Tubing & filters
  • Large volume containers
  • Disposables (Bioprocess – single use)
  • HDPE, LDPE, PP, Plastic bags & containers
  • In process manufacturing components