Container / Closures

In order to obtain successful regulatory approval for new drug applications, packaging interactions with the drug product should be evaluated to ensure product safety.

Smithers Rapra has extensive expertise in delivering high quality, customised, extractables and leachables work packages to meet your specific regulatory requirements.

The degree of interaction between the drug product and the primary packaging is dependent on the product type, as is the risk to the patient. The FDA summarises this in a table which is reproduced below:

Packaging Component-Dosage Form Interaction Comparison Matrix

Degree of Concern Associated with Route

Likelihood of Packaging Component-Dosage from Interaction

High

Medium

Low

Highest

Inhalation Aerosols and Solutions; Injections and Injectable Suspensions

Sterile Powders and Powders for Injection; Inhalation Powders               

 

High

Ophthalmic Solutions and Suspensions; Transdermal Ointments and Patches; Nasal Aerosols and Sprays

 

 

Low

Topical Solutions and Suspensions; Topical and Lingual Aerosols; Oral Solutions and Suspensions      

Topical Powders; Oral powders             

Oral Tablets and Oral (Hard and Soft Gelatin) Capsules

FDA guidance for industry - container closure systems for packaging human drugs and biologics 

Smithers Rapra has experience of working with and analysing a wide range of drug product types, examples include:

  • Parenteral drug products including cytotoxic compounds, biologics, small molecules
  • Inhalation drug products (pMDIs, DPIs, inhalation solutions).
  • Ophthalmic drug products
  • Topical products
  • Oral solutions and suspensions

We are the rubber and plastics experts, our history is polymers. With the majority of medical packaging being comprised of polymeric or elastomeric materials, this makes us the number one independent contract laboratory for your testing. We have experience with a wide range of polymeric and elastomeric materials including, but not limited to:

Thermoplastics:

polypropylene (PP), low density polyethylene (LDPE), high density polyethylene (HDPE), cyclic olefin copolymer (COC), polycarbonate (PC), polystyrene (PS), styrene acrylonitrile (SAN), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), acrylonitrile-butadiene- styrene (ABS), polyvinyl chloride (PVC), polyamide (nylon), polyvinyl acetate (PVA), polyether ether ketone (PEEK), polytetrafluoroethylene (PTFE)

Thermosets:

thermoset polyurethane (PU), silicone resins, epoxy and polyester resins

Rubber and elastomers:

butyl rubber (IIR) (including chloro- and bromo-), nitrile (NBR), silicone, butadiene rubber (BR), polyisoprene (IR), ethylene propylene diene monomer (EPDM), flouroelastomers (FPM/FKM), thermoplastic polyurethane (TPU), thermoplastic elastomer (TPE)

All critical parts of the primary packaging should be considered, this includes any external labels which contain inks, adhesives and lacquers as these have the ability to migrate though the polymer packaging into the drug product.

Typical Extractables and Leachables Testing

Smithers Rapra follow best practice guidelines, such as those provided by the PQRI for OINDP and USP draft chapters <1663> and <1664>.

The extractables study:

  • Design and execution of the extractables study on critical components of the primary packaging, covering inorganic and organic extractables.
    • Determination of the Analytical Evaluation Threshold (AET) from the Safety Concern Threshold (SCT)
    • Use of a number of extraction methods, employing multiple analytical techniques, as no one analytical technique is capable of detecting all extractable substances
    • Provision of a detailed technical report, containing full results and chromatograms
    • Option for undertaking a literature based toxicological assessment of the detected extractables to identify target leachables

The leachable study:

  • Development and validation of methods for the assessment of leachables in the drug product according to ICH Q2(R1)
  • Analysis of stability time point samples for leachables. 
Contact Smithers Rapra about Extractables and Leachables

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