Doug Hostetler

Principal SME, Medimop/SA

January 24, 2012

According to the Code of Federal Regulations Title 21 Food and Drugs Part 211.94(a) Subpart E Control of Components and Drug Product Containers and Closures, drug containers must not react or add to a drug product in a way that alters the drug’s safety or quality.
Concerns related to the packaging system can include:

– Poor chemical durability
– Use of silicone lubricants and impact to product quality
– Compatibility concerns related to biopharmaceuticals
– Potential for leaching and interaction with drug products
– Drug product shifts in pH due to glass dissolution
– Reduced potency from adsorption of drug product onto glass surface
– Breakage, scratches or particles resulting from packing, transport and filling

To help assure proper package selection and avoid potential incompatibilities between product and closure systems, a screening comparison study can be completed.  This typically includes an 8-week investigational study that will help manufacturers determine the best elastomer selection for their drug product.

First, a study questionnaire is completed by the manufacturer to help the selected lab gain knowledge of the drug product. From this information, a list of potentially suitable elastomeric formulations is chosen for the study.

A gross compatibility study is designed to accelerate any incompatibilities that may exist between the drug product and the potential packaging. To accomplish this, the customer must supply bulk product or placebo for testing. Processing of components is then simulated and sample vials are inverted to maximize contact between the elastomer and the drug product.  Accelerated conditions are used to help speed the analysis.

A thorough analysis may include the following screening techniques:

  • Inductively Coupled Plasma Screening
  • pH Shift
  • Turbidity
  • Ultraviolet Spectrum
  • Visual Inspection in High Intensity Light
  • Ion Chromatography Screening
  • NonVolatile Residue / Infrared Spectroscopy 
  • High Performance Liquid Chromatography / Mass Spectroscopy Screening*
  • Gas Chromatography/Mass Spectroscopy Screening*

Appropriate sample preparations for these analyses will also need to be established as part of the study.  

*These screenings involve the use of a general method, which may qualitatively uncover extractables that are present. West recommends a more thorough leachable analysis be performed on the chosen closure candidate during later evaluations.