Page 120 - Assurance of Sterility for Sensitive Combination Products and Materials

104 Assurance of sterility for sensitive combination products and materials

pharmaceutical. Depending on the type of product and risks, the assessment
may range from a description of the composition of the packaging mate-
rial and an evaluation of cytotoxicity to a detailed risk analysis with tar-
geted testing depending on the type of patient contact and its duration. ISO
10993-1 Evaluation and testing within a risk management process [68] provides
a framework for biological evaluations. The ISO 10993 series of documents
provides guidance on appropriate testing to address specific identified risks.
ASTM F2475 Standard Guide for Biocompatibility Evaluation of Medical Device
Packaging Materials [69] helps with specific aspects of packaging materials.
The evaluation of biocompatibility can be a complex undertaking and it
is recommended to research specialized literature [70] and consult experts.

5.3.4.4 Extractables and leachables
The degree of rigor needed in determining the potential interactions
between packaging and the drug product is a function of the dosage
form and the route of administration as well as stability testing require-
ments. The FDA Guidance for Industry on Container Closure Systems for
Packaging Human Drugs and Biologics [24] includes three degrees of con-
cern in function of the dosage form (Table 5.2). The EU Guideline on
Plastic Immediate Packaging Materials [71] describes the requirements for
marketing authorization applications to be submitted for packaging mate-
rials in direct contact with the active substance or medicinal product. The
guideline includes a decision tree based on the dosage form defining the
type studies and documentation required. Nonsolid active pharmaceutical
ingredients (API) require the complete qualitative composition of the
plastic material if pharmacopeia compliance of the immediate packaging
material cannot be demonstrated. Many leachables are detected during
initial material qualification studies, however, some negative interactions
might only appear during stability studies. Toxicological data are required
for extractables and leachables. Selecting materials with a known chem-
ical characterization can significantly shorten the development process.
Selecting materials that are compliant with food contact regulations or
with compendial pharmacopeia monographs can reduce the regulatory
burden significantly.

5.3.4.5 Performance qualification
The objective of performance testing is to demonstrate maintenance of
integrity of the SBS by testing the entire packaging system, which includes
the SBS packaged and its protective packaging, after handling, distribution,