The easy answer is, “as early as possible,” but the real answer requires some discussion. The FDA Guidance for Industry, Container Closure Systems for Packaging Drugs and Biologicals recommends that each new drug application (NDA) or abbreviated new drug application (ANDA) contain enough enformation to demonstrate that a proposed package and its components are suitable for the intended use. In summary, the container-closure should adequately protect the dosage form, be composed of materials safe for use with the dosage form and route of administration, and function properly if it has a performance feature. Some questions that arise from the guidance include:

• Does the container-closure system protect the dosage form from environmental challenges (e.g., moisture, light, oxygen, shipping)?
• Is the dosage form identified in the Guidance as a higher (e.g., ophthalmic solution, transdermal, or nasal) or highest (e.g., inhalation or injectable) risk for packaging concerns?
• Does the container-closure system play a functional role in delivery of the drug product such as with inhalations and transdermals?

The more “yes” answers to questions such as these point to the need for earlier consideration/selection of the container-closure system during development. Current regulatory initiatives (e.g., quality by design, risk assessment) provides further urgency to an early initiation of container-closure consideration. Ultimate product quality is enhanced when the container-closure system is an integral part of early development studies. A better defined and robust design space for manufacturing will typically follow that may provide acceleration of the regulatory review process.

There is a tremendous range of development program strategies due to the variety of dosage forms, formulations, clinical study requirements, and therapeutic objectives. Therefore, it is not possible to dictate the exact point to start considering and initiate development of the commercial container-closure. A dry-powder inhalation product may look much more like the registration product in formulation and container-closure during Phase I when compared with a solid oral dosage form which may be neat API in a hard gelatin capsule during Phase I. However, it is reasonable to say that any dosage form should be seeing the initiation of container-closure selection during Phase II and that dosage forms where the container-closure plays a functional role during Phase I.