The qualification and quality control of packaging components are essential activities to receive either CDER (FDA Center for Drug Evaluation and Research) or CBER (FDA Center for Biologics Evaluation and Research) approval of a container closure system to be used in the packaging of a human drug or biologic.  The relevant data is provided within the application (NDA, new drug application, ANDA, abbreviated drug application and BLA, biologics license application) to the FDA.  The overall focus for FDA approval is to provide data that the proposed container closure system and its components are suitable for intended use.

Suitability for intended use can be summarized as follows:

• Adequate protection of the dosage form—e.g., temperature, light that can cause a degradation in the quality of the dosage form over its shelf life
• Compatible with the dosage form– will not interact sufficiently to cause unacceptable changes in the quality of either the dosage form or packaging component
• Composed of materials considered safe for use with the dosage form and route of administration (e.g., oral, parenteral)– materials that will not leach harmful or undesirable amounts of substances. This consideration is especially important for those packaging components which may be in direct contact with the dosage form, but it is also applicable to any component from which substances may migrate into the dosage form (e.g., an ink or adhesive).
• Performance feature shown to function properly—assembled container closure system shown to function properly, e.g., an autoinjector.

Compendial or pharmacopeial testing on packaging materials are requirements for most regulatory submissions.  The United States Pharmacopeia (USP) is a scientific, nonprofit organization that sets federally recognized public standards of quality for medicines, dietary supplements, and foods.

Below are U.S. Pharmacopeia/National Formulary standards used in the testing for “suitability for intended use” for container closure systems; tools to guide your qualification and quality control of packaging components for drugs and biologics:

General Notices: Preservation, Packaging, Storage, and Labeling

General Tests and Assays

<1> Injections

<51> Antimicrobial preservations—Effectiveness

<61> Microbial limit tests

<71> Sterility tests

<87> Biological reactivity tests, in vitro

<88> Biological reactivity tests, in vivo

<161> Transfusions and infusion assemblies

<381> Elastomeric closure for injections

Biologic Test Procedures
<601> Aerosols

<661> Containers

• Light transmission
• Chemical resistance—plastic
• Biological tests—plastics and other polymers
• Physiochemical tests—plastics
• Containers for ophthalmic—plastics
• Polyethylene containers
• Polyethylene terephthalate bottles and polyethylene
• Single unit containers and unit dose containers for non-sterile
• Solid and liquid dosage forms

<671> Containers—Permeation, moisture

<691> Cotton

<771> Ophthalmic ointments

<1041> Biologics

<1151> Pharmaceutical dosage forms

As the demonstration of suitability for intended use is essential to obtaining regulatory approval, the successful execution of appropriate qualifications of the packaging components, as well as the implementation of effective quality control processes is a business and quality system imperative to commercialize your drug product.

Book a 15-minute discovery call today to explore how our elite professionals at FlexPro can support your packaging initiatives.

Reference:  Guidance for Industry–Container Closure Systems for Packaging–Human Drugs and Biologics, CHEMISTRY, MANUFACTURING, AND CONTROLS DOCUMENTATION