Guidance for Clinical Trials Packaging
As part of a document for IND applications, FDAï¿½s new guidance covers packaging for clinical trials.
A new FDA guidance describes the packaging and stability information drug manufacturers need to provide to the agency during clinical trials.
This advice is part of a document that indicates what chemistry, manufacturing, and controls information should be included in Investigational New Drug (IND) applications for Phase 2 and Phase 3 studies.
The guidance, posted May 20, 2003, can be viewed at www.fda.gov/cder/guidance/3619fnl.pdf.
For INDs relating to Phase 2 studies, manufacturers should provide a brief description of the container closure system in an information amendment. When changes are made to the container closure system that may affect product quality, they should be submitted in an information amendment. Otherwise, packaging changes can be submitted in an annual report.
Also for Phase 2 studies, manufacturers should submit a description of the stability program that supports the studies. It should note the tests and analytical procedures used, test time points, storage conditions, and duration of the study.
Any stability data for clinical material used in Phase 1 studies that were not reported during Phase 1 should be submitted in an information amendment. If degradation of the drug product occurs during manufacture or storage, it must be taken into account when establishing acceptance criteria and monitoring quality.
There is no formula that indicates which tests should be included in the stability program. That should depend on the nature of the drug product and its dosage form.
For INDs relating to Phase 3 studies, a brief description of the packaging and labeling process for clinical supplies should be provided in an annual report. For sterile products, an information amendment should be submitted for changes to the sterilization process. Information on validating the sterilization process is not required at this time. It should be included at the New Drug Application (NDA) phase.
If the container closure system used in Phase 3 differs from that used in Phase 2, it should be updated in an information amendment. If packaging changes are made during Phase 3 studies, an information amendment should be submitted if there might be an effect on product quality. Otherwise, the changes can be noted in an annual report.
If packaging components such as glass and polyethylene containers that have compendial standards are used, compliance with those standards should be shown. If reference is made to information in a Type III Drug Master File (DMF), an authorization letter from the DMF holder should be provided. The agency may seek information for nonstandard delivery systems such as metered-dose inhalers and disposable injection devices. If the drug will be dispensed by a device, the container closure system used in the Phase 3 study should be similar to the one intended for the marketed product.
If the stability program for Phase 3 differs from that used in Phase 2, changes should be provided in an information amendment. The amendment should describe which attributes are being investigated in the stability program. The appropriate controls and storage conditions must be demonstrated. Tests unique to the stability program need to be defined and described.
Stability data used in Phase 2 studies that were not reported at the time should be provided in an information amendment. Stability data used in Phase 3 should be reported in annual reports in a tabular format as soon as the data become available. Some products may need one-time stress testing to assess potential for physical or chemical changes. This may include testing for effects of high temperature, high humidity, or oxidation. Relevant data should be provided in an annual report.
At this point, a stability protocol to be used for formal stability studies at the NDA stage should be developed. It should be submitted in an information amendment before or during Phase 3 studies. It should be discussed at the end-of-Phase-2 meeting with the agency, especially if bracketing or matrixing will be used.
If labeling information for Phase 2 or Phase 3 is different from that in Phase 1, it should be updated in an information amendment.