Location of the Clinical Trial

Depending on which country (or countries) the clinical trial is due to take place in, there may be varying regulations surrounding the testing that must be performed on the clinical trial material. This can have a bearing on the manufacturing process.

Certain tests may be performed on the final product in the form in which it would be delivered to the clinic (i.e., the final product containers). However, other tests will be required on the raw materials that go into the manufacture of the clinical trial material. The possible items are a long list: the cell bank, viral seed stock, viral bank, cell culture media, reagents, fetal bovine serum, downstream purification buffers, and formulation buffers.

Location can also have implications for the shipping logistics that will be involved in delivering material to the clinical trial site. These are good questions to consider:

• Under what conditions will the material be stored?
• Will it be lyophilized and stable at room temperature?
• Must it be stored and shipped frozen?
• What validation will be required to prove that shipping and storage conditions are not having deleterious effects on the clinical trial material?
• What will be the ambient temperature conditions, depending on what country the trial is taking place in?
• What distribution channels are available to ensure safe, efficient delivery of intact, functional clinical trial material?

Duration of the Clinical Trial

Estimate the duration of the clinical trial so that you can develop the right kind of stability study. This study provides supporting data for the functionality of the clinical trial material over the length of time that the investigational medicinal drug product will be held in storage before administration to the patient.

Schedule for Conducting the Clinical Trial

The target date for starting clinical testing is crucial. Work closely with the CMO to ensure you both agree on target date for delivering released product. You must also establish if the clinical trial date is a fixed date or if it is flexible. The start date may change if you need to wait until sufficient patient numbers are recruited into the trial, or if there is a delay in funding for the next milestone in the clinical development program. If the clinical trial date is not firmly fixed, you must consider the duration of the stability study that will be required to ensure that the latest possible date for patient administration will be covered by the supporting evidence.

Nature of Administration

Another crucial element of the clinical trial design for you and your CMO to discuss is how the investigational medicinal drug product will be administered to the patient. Is the CMO expected to provide the clinical trial material in the final dosage form, or will they simply manufacture the product to the stage of bulk drug substance for delivery to another company, or back to the sponsor, for the final formulation and filling stage?

Hold detailed discussions at this stage to determine the specification for the final product container, and how the CMO will ensure that the correct dose will be present in each container. For example, if a specific viral titer is to be delivered to each patient, how accurate will the volume be that is dispensed into each container, and has the extractable volume of the container been determined? If the clinical trial material is a liquid supplied in a glass vial, ask how much material will be left in the vial and in the holding volume in the syringe once the clinician has extracted the liquid from the vial.

If the trial is to take the form of a prime and boost delivery, then take appropriate measures to ensure that the stability study covers this lag phase between the first and last doses. Obviously, the manufacturing scale will also have to be larger if more than one dose is required per patient.