A written or verbal prescription (or medical order) is used depending on state pharmacy law requirements. In the E2 Dispensing model, clinical supplies are patient-specific and are dispensed on a per-patient basis instead of preparing and shipping bulk quantities of clinical supplies to depots or clinical sites. The prescription or medical order includes the name and strength of the medication being studied, as well as any other elements required by state pharmacy law. The dispensing pharmacist uses the randomization schedule and the instructions of the protocol or the pharmacy manual to dispense the correct clinical supplies.
Clinical supplies may be automatically refilled and shipped based upon the prescription, the clinical protocol, or the pharmacy manual’s instructions. As required by state pharmacy law, a pharmacist will counsel the patient who received the clinical supplies and will monitor patient dropouts, changes, compliance, etc. to verify ongoing applicability of refills and continuation or discontinuation of clinical supplies.
The E2 Dispensing model eliminates almost all clinical supplies waste previously associated with the clinical supply chain, as there is no packaged and labeled warehouse inventory or clinical site waste.
E2 Dispensing studies follow state dispensing laws and regulations requiring that patients be counseled by licensed pharmacists to ensure compliance and adherence with their medication. Licensed pharmacists also ensure that patients receive and understand the instructions on the proper storage and handling of their clinical supplies. It is important to note that all pharmacists providing counseling are blinded and do not have access to the dispensing pharmacy records
The central-fill pharmacy is responsible for ensuring that blinded clinical supplies information remains secure, protected, and confidential. Only the central-fill pharmacists and pharmacy technicians will have access to the blinded clinical supplies information for dispensing and unblinding purposes, unless otherwise required or contracted. The counseling pharmacist or pharmacy technician, as well as any clinical sites, clinical healthcare providers, the local pharmacy, if used, and the sponsor all remain blinded.
Blinded E2 Dispensing trials still use randomization schedules to ensure equal distribution amongst treatment groups and to prevent bias. With E2 Dispensing, however, there is no need to ship clinical supplies in blocks or to create blocking factors related to clinical site shipments.
In accordance with the majority of standard practice requirements for dispensed medications promulgated by the state boards of pharmacy, the dispensing pharmacy’s dispensing system is used for the administration, tracking, and record keeping of the control, disposition, and documentation of used and unused clinical supplies. Some additional data elements may be added to tie the randomization information (e.g., the randomization number, randomization code, etc.) and returns information to the patient.
If required by the clinical protocol, an Interactive Response Technology (IRT) can be used in addition to or in place of the pharmacy’s dispensing system.
For clinical supplies dispensed in the US and as required by 21 C.F.R. §312.6, container labels will include the statement: “Caution: New Drug--Limited by United States law to investigational use.” In addition, the clinical supplies are properly labeled in accordance with state pharmacy laws and regulations. For example, North Dakota law states the following requirements for prescription labels:
N.D. Admin. Code §61-04-06-01. The prescription label. Controlled drugs and noncontrolled drugs dispensed pursuant to a prescription must bear a label, permanently affixed to the immediate container in which the drug is dispensed or delivered and which is received by the purchaser or patient, which must include the following:
1. The name and address of the dispenser or pharmacy;
2. The serial number of the prescription;
3. The current date of its filling or refilling;
4. The name of the prescriber;
5. The name of the patient;
6. The directions for use, including precautions, if any, as indicated on the prescription;
7. The initials or name of the dispensing pharmacist;
8. The telephone number of the pharmacy; and
9. The drug name and strength and quantity.
The prescription label for controlled drugs, in addition to the above, must comply with the label requirements of the Federal and State Uniform Controlled Substances Act, including the transfer warning auxiliary label.
All mail-order prescriptions, require that a licensed pharmacist be available to speak with patients or caregivers to answer questions, provide advice, and offer pharmacist counseling. With E2 Dispensing, a pharmacist proactively calls patients to ensure that medication is received, stored, used, and returned according to the clinical protocol as well as the pharmacy manual.
E2 Dispensing eliminates the potential for mishandling of supplies by clinical sites and the often-overlooked storage conditions of clinical supplies during the transport from the clinical site to the patient’s home.
The counseling pharmacist or pharmacy technician verifies the receipt of the supplies with the patient, documents how much they used, how much they did not use, and discusses with them how to return their supplies either to the central-fill pharmacy or their RxE2-contracted local pharmacy. If a discrepancy is noted, the counseling pharmacist will follow up with the patient and the local pharmacy, if used. If a local pharmacy is used, the local pharmacy will forward the patient accountability information on to the central-fill pharmacy.
The dispensing pharmacist or pharmacy technician at the central-fill pharmacy will perform clinical supplies reconciliation by performing patient accountability verification as well as accounting for the bulk clinical supplies.
The central-fill pharmacy documents all accountabilities and reconciliations and is responsible for following up on and documenting all discrepancies. The central-fill pharmacy also provides accountability and reconciliation reports as needed.
Retain samples are a GMP requirement for the packaging and labeling of GMP produced material and as such, the manufacturer of the bulk clinical supplies will keep a retain of the packaged and labeled bulk clinical supplies produced and shipped to the central-fill pharmacy.
Retain samples of the clinical supplies dispensed to patients are not required.
No. However, E2 Dispensing Pharmacies are considered clinical sites and, as such, follow GCP requirements in addition to state pharmacy regulations. GMP requirements apply to GMP manufacturing sites where GMP trained individuals may manufacture, package, label, and ship clinical supplies.
E2 Dispensing is a cost-effective option for the packaging, labeling, and dispensing of clinical supplies. For almost all of today’s clinical studies, E2 Dispensing will reduce direct costs by eliminating waste of clinical supplies and will reduce indirect costs by eliminating the complexity associated with packaging and labeling supplies for clinical sites. For example, E2 Dispensing no longer requires most of the upfront planning, such as label and kit creation and design, site-seeding forecasting, and pooling or just-in-time clinical supply strategies needed for traditional packaging and labeling.