IU Health Investigational Drug Services

Monitor Visits

All monitoring visits must be scheduled in advance. If an initial monitoring visit is required within a defined period following the first patient’s treatment, IDS must be notified at the time of scheduling. Otherwise, IDS requires a minimum of four (4) weeks’ advance notice. Visits are scheduled by emailing the IDS location managing the study,ids@iuhealth.org or Riley-IDS@IUHealth.org, and will adhere to the Indiana Eastern Time zone. Remote monitoring visits are preferred. Monitors conducting on-site visits must bring a laptop capable of accessing Vestigo®. IDS reserves the right to refuse entry if a monitor arrives outside of their scheduled appointment time due to limited on site space.All requests for study‑related documentation (including, but not limited to, temperature logs, shipping and receipt documentation, training records, pharmacy manuals, and investigational product accountability records) must be identified, requested, and reviewed during the scheduled monitoring visit. IDS does not provide post‑visit documentation, photographs, screenshots, or ad‑hoc information requests that were not addressed during the monitoring visit. IDS staff will not capture or transmit images of source materials, storage areas, or documentation outside of a scheduled visit. Monitors are responsible for ensuring all required information is reviewed and obtained during the monitoring visit. IDS expects sufficient handoff between outgoing and incoming monitors to ensure continuity of agreed‑upon procedures without requiring re‑review or revision. All documents provided to a previous monitor are expected to be transferred to the incoming monitor and filed within the Trial Master File (TMF) to ensure availability for future monitoring activities. The monitor is responsible for ensuring that IDS is provided with the most current, sponsor‑approved version of the pharmacy manual prior to or during the monitoring visit.
 

Interactive Response Technology (IRT)

For protocols that require IDS participation in an Interactive Response Technology (IRT), individual access should be provided to the lead pharmacist and all pharmacy technicians. On occasion, additional pharmacists may require access. Failure to provide appropriate IRT access may result in treatment delays. IDS responsibilities are limited to confirmation of study drug receipt or quarantining IP if alarming upon arrival, damaged upon arrival, or if involved in a temperature excursion during storage or transport. IDS personnel cannot support enrolling subjects, entering subject data, entering subject/ drug accountability data,or performing reconciliation within an IRT or EDC when accountability isdocumented in Vestigo®. IDS cannot support entering data into a system to determine treatment, lot number, or kit assignment.

Per Joint Commission Medication Management Standard MM.06.01.05 EP2, the IDS and/or IU Health pharmacies will coordinate storage, dispensing, labeling, and distribution of all Investigational Product (IP) for a protocol. If an IP requires special handling, such as nuclear or cell agents needing specific storage, preparation or testing, it may be stored in a designated hospital area outside of IDS. Any product on a trial that requires pharmacy to report documentation such as lot number, expiration, manufacturer, or temperatures must go through IDS.

Special agents like nuclear or cell agents requiring unique handling are stored in designated hospital areas. Trial products needing pharmacy documentation—such as lot number, expiration date, manufacturer, or temperatures—must be processed through IDS.

New protocols should be submitted to IDS prior to IRB submission for feasibility and/or a budget for pharmacy services. Contact the IDS team early in the study planning phase. Early involvement allows for better planning and identification of potential challenges in drug management or protocol logistics. This should be done using the IDS Redcap form: IDS Pharmacy Budget and Feasibility Request. Please be advised that the IDS Team requires all study documents before providing accurate feasibility or budget assessments. Note that drug costs at the time of purchasing will be passed onto the sponsor, which may be more than the quote provided on the budget document. IDS cannot control price fluctuations.

The IDS Lead Pharmacist prepares instructions for pharmacy technicians regarding the preparation and dispensing of IP. The lead pharmacist reviews Physician Orders for accuracy when ordering IP or creates prescription forms used for ordering outpatient IP(s).

To streamline the study initiation process, all paper order set documentation should be completed and quality assurance (QA) checks performed before IRB approval. After IRB protocol approval and the start-up meeting, the lead pharmacist finalizes internal standard operating procedures (SOPs) and prescription forms. The designated personnel will submit the order sets for electronic health record build, when applicable. Protocol amendments, pharmacy manuals, investigational brochures, and other related documents must be sent to IDS along with IRB approval documentation, if required. Amendments at study start up may affect study activation timelines due to potential rework.

IDS staff must be invited to sponsor site initiation visits, internal initiation meetings (for sponsor–investigator or cooperative group studies), and CRC Inservice sessions, if applicable. IDS must attend pharmacy-specific training to discuss investigational drug dispensing logistics. The study team is responsible for addressing questions about thaw and preparation times to schedule realistic patient visit times. All verbal agreements require email confirmation before IDS can dispense drug. Specific tasks will be delegated by the PI and agreed upon by the lead IDS Pharmacist after consultation with the study team. IDS may request a dedicated agenda item or separate review and suggest providing at least two weeks’ notice for meetings.

Patient Orders/Prescriptions Dispensing Process

The Study Coordinator or Research Nurse sends a prescription via fax, email or electronically to IDS signed by an authorized prescriber. Email or electronic orders are preferred. Electronic signatures are not accepted for controlled substance prescriptions. Study teams should provide an estimated pick-up time, or time when they’d like to have medication in their possession, when ordering, enabling IDS to prioritize preparation. Patient appointment times alone aren't specific enough. Requests for medication are processed in the order in which they are received when there are multiple medications due at the same time. Teams should factor in product thawing and preparation times when determining pick up or administration times. IDS asks that all patients are scheduled in a way that allows IP to be dispensed between 8 am and 4:30 pm if the study was set up to occur during office hours. Once an order and assignment (if applicable) are received, and the patient is confirmed to be appropriate for treatment to be prepared, the pharmacy technician pulls preparation instructions, IP and other supplies needed and documents accountability. A delay in receiving patient assignments or orders from the study team will cause a delay in dispensation as this is required before preparation can begin. A pharmacist checks IP and verifies accountability documentation. For sterile or non-sterile compounding, the technician prepares the IP according to instructions, and the pharmacist checks the final product. Per CFR 312.6, all IP dispensed from IDS will have, “Caution: New Drug - Limited by Federal (or United States) law to investigational use.” After the final pharmacist check, pharmacy staff notifies the study team that the IP is ready for pick-up and places it in a bag in the pharmacy pickup area. Research staff then picks up the IP from the pharmacy.

For orders administered in the infusion area, orders are entered as part of a treatment plan. After the patient’s labs are reviewed, the research nurse completes their review, the infusion nurse confirms the patient is ready, and the infusion pharmacist completes a clinical check, the study medication can be dispensed and prepared. Once the dose is prepared and checked by the pharmacist, it is delivered to the appropriate infusion pod for administration, either placed in a locked med drawer or handed directly to the patient’s nurse or charge nurse. Any delays in order activation or assignment receipt could result in a delay in dispensing or preparation activities.

Compounding Hazardous Products

Closed System Transfer Device (CSTD) system will be used to compound all injectable hazardous agents in a biological safety cabinet to minimize exposure using proper technique and equipment in accordance with USP 800, IU Health Policy, and IDS procedures. There is a potential risk of exposure wherever hazardous medications are received, stored, prepared, administered, or disposed of. Exposure may occur via inhalation of an aerosolized drug or droplets, absorption through the skin, accidental injection, or ingestion through contact with food or contaminated hands.
Per the National Comprehensive Cancer Network (NCCN) investigational service consensus recommendations, research pharmacies should follow their institution’s applicable policies and risk assessment for handling of any IP that is deemed hazardous.

• “In the absence of incompatibility evidence between the CSTDs fluid pathway components and IP, CSTDs will be used for compounding as dictated by local policy.”
• “IDS should use their locally sourced CSTD supplies due to familiarity and increased safety when compounding and administering hazardous drugs.”
• "Clinical trial sponsors should be willing to prospectively test IP with CSTD products if compatibility is a concern."
  
  

Enteral Medication Administration

IDS will utilize the ENFit connectors for enteral medication administration as a part of a universal standard (ISO 80369-3) that ensures only enteral devices can connect to each other.

Accountability

IDS stores all Investigational product (IP) by the IU IRB number. IDS uses Vestigo®, for the management of drug therapy associated with approved research protocols. Vestigo® is 21 CFR Part 11 compliant and supports protocol management functions including electronic inventory control, investigational product accountability, dispensing and labeling, protocol billing management, and reporting.

IP accountability records are maintained electronically in accordance with FDA and ICH GCP requirements and NCI guidance, when applicable. Accountability is documented only for IP and diluents that are provided or reimbursed by the sponsor and come from IDS. IDS does not document accountability for ancillary supplies, packaging materials, or labels provided by the sponsor IP accountability records are maintained in their original electronic format and are reviewed electronically as standard practice. Printed copies may be generated solely for audit, inspection, or regulatory review when required. IDS personnel do not sign, modify, or annotate accountability records outside of established audit or regulatory requirements. IDS will not complete sponsor forms (e.g., IP preparation worksheets), but necessary information from these forms may be included in the DARF as appropriate. 

Expiration/Retest Date Changes

The IDS pharmacy will document changes to expiration/retest dates on accountability records based on documents provided by sponsors. IDS will not relabel if IP needs to be physically relabeled. Relabeling can be done by the sponsor representative if desired.

Maintenance Fees

The IDS pharmacy will charge maintenance fees until all IP has been dispositioned, all questions or concerns regarding the study file or documentation are answered, and the pharmacy is authorized to close out by the sponsor/sponsor representative. Unless otherwise stated, maintenance billing will start approximately one month after the SIV or once IP has been received; whichever comes sooner.

Chain of Custody

The IDS service date or dispense date is the date IP is removed from IDS inventory. This may not be the actual date the patient receives the medication. Research staff will be responsible for documenting any further chain of custody documentation if needed.

Documentation

Study regulatory documents are maintained by the study team either in the regulatory binder or within an electronic regulatory system (e.g., Advarra eReg). These documents include, but are not limited to, IDS staff curricula vitae, GCP and Human Subjects Protection training records, and professional licenses. Access to regulatory binders or regulatory documentation must be coordinated through the study team. Regulatory binders are not maintained by IDS and will not be available for review during IDS pharmacy monitoring visits. An individual must request EReg access and complete training to receive a username. Access requests can be completed here.

IDS Pharmacy will provide access only to the most current versions of the IRB-approved protocol, investigator’s brochure, pharmacy manual, and other supporting documents. Newsletters and other communications will not be available through IDS Pharmacy. These, along with previous versions of documents and Delegation of Authority records, can be found in the Principal Investigator’s (PI) regulatory binder.

Training for IDS Pharmacy staff is focused on information relevant to tasks delegated by the PI. Only training related to the storage, preparation, or dispensing of the IP will be documented for all IDS staff. The lead pharmacist or their designee conducts training during routine staff meetings, and records are maintained in Vestigo competencies. Training documentation is filed in the IDS Pharmacy for each protocol and may be reviewed during monitor visits only.

Records Storage

Study materials (drug receipt records, orders, etc.) are returned to the Principal Investigator at study close‑out for long‑term retention in accordance with applicable regulatory requirements. IP accountability records and temperature monitoring records are maintained electronically within the Vestigo® system and/or as secure electronic files for the required retention period and remain available for audit or inspection, as applicable.

Event Reporting

When IDS identifies a potential protocol deviation, they will inform the PI and research team and update the PI and team as the investigation/corrective actions are put into place. IDS will not report events/deviations to the IRB directly; it is the responsibility of the PI and study team to meet IRB reporting requirements. Concerns may be escalated to the PI if necessary. Unblinded information can be shared with the IRB or an unblinded sponsor representative if required.

IDS anticipates a reasonable turnaround time for reporting details of the root cause, as well as corrective and preventative actions. This allows the team sufficient time to thoroughly investigate the event and considers additional responsibilities staff may have. IDS expects at least 5 business days to report details to the IRB unless otherwise stated by the IRB, and at least 2 business days to respond to sponsors.

Site Blinding Plan/Procedures

The Principal Investigator delegates the responsibility of managing the Investigational Product per protocol to the IDS Pharmacy. The procedures below are followed to protect the blind:

• The pharmacy areas are contained with restricted access. Only unblinded pharmacy staff have access to the pharmacy and investigational product and records.
• Non-IDS staff members will need to schedule on-site visits to access accountability information. Alternate methods must be discussed with the lead pharmacist and described in the Site Blinding Plan (if applicable).
• Pharmacy office equipment is kept securely within the pharmacy and is accessible by unblinded pharmacy staff only
• All IDS Pharmacy staff are trained and understand the importance of written and verbal communication between blinded and unblinded study team members. Only necessary communication will occur with the blinded study team

Patient Returns

Good Clinical Practice (GCP) guidelines state “The investigator/institution and/or a pharmacist or other appropriate individual should maintain records of the product's delivery, the inventory, the use by each participant, and the return to the sponsor and destruction or alternative disposition of unused product(s). These records should include dates, quantities, batch/serial numbers, expiration dates (if applicable) and the unique code numbers assigned to the investigational product(s) and trial participants.” E6R3 2.10.4. IDS will not save any used IP, packaging or materials from patient returns. The IP and/or packaging will not be saved for monitor reconciliation or returned to the sponsor. These will be destroyed following the standard Document and Destroy Procedure. IDS will not accept any returns that are considered a biological hazard, or any IP, packaging, or materials dispensed from a third-party organization (any entity that is not IDS or any IDS satellite locations).
 

Used IP from Sterile or Non-Sterile Preparations

IDS will not save any IP or packaging that was used for preparation. Once the product has entered the preparation area, no materials will be removed or saved. These materials are placed for destruction upon preparation.

Unused/Expired IP

Once unused or expired IP is approved for destruction by sponsor/monitor, it will be documented and destroyed following the Document and Destroy Procedure by two IDS staff members or an IDS staff member and the monitor. If the sponsor does not come on site to destroy then unused expired IP will be destroyed 90 days after expiration, and unused IP for a closed study will be destroyed six months after date of protocol IRB closure by two IDS staff members to assist IDS in maintaining appropriate storage space for active inventory. If IP needs to be shipped back from IDS, the sponsor must provide a prepaid shipping label and should plan to send a monitor onsite to pack the product.

IP Document and Destroy Procedures

The first IDS Staff member will count the patient return of IP, document the quantity on the accountability log, and place the IP as ready for second review. A second IDS staff member will count the IP, doucument the quantity on the accountability log and document and place for destruction. If a difference occurs between the two counts, destruction will be halted. The discrepancy will be investigated and resolved before continuing with destruction.

IU Health has established specific policies and procedures for the disposal of drugs and drug preparation within pharmacy areas. IDS is required to comply with these institutional policies for when handling study drugs.

Document/Paper Shredder

All paper generated by IDS, including documents containing subject or study information, is placed in an IU Health approved sealed container. The contents are transported to the contracted facility for shredding.
 

Bulk Hazardous Waste

This includes those agents classified by the EPA's RCRA regulations as "regulations as "regulated" and all Hazardous agents prepared by IDS as well as any investigational drug agent managed by IDS and per IU Health Disposal of Pharmaceutical Waste policy. These agents are placed in Hazardous labeled containers that are segregated from all the containers. These are placed in hazardous labeled bins and transported intact to the contracted facility for incineration (Daniels, Heritage Environmental Services INC. 7901 W. Morris St. Indianapolis, IN 46231)

Trace Hazardous Waste

The items used in the preparation of hazardous drugs but have not been exposed to spills or liquid contaminants (e.g. gowns, gloves) and empty containers and packaging for Hazardous agents that have come in direct contact with the agent. These are placed in Hazardous labeled trash bins and transported intact to the locally contracted facility for incineration (Daniels Heritage Environmental Services INC. 7901 W. Morris St. Indianapolis, IN 46231.)

Controlled Substance Waste

Waste of an investigational product that is regulated by the Drug Enforcement Administration or considered to be a controlled substance by the sponsor will be placed in a specially designed receptale that renders the product unrecoverable, non-retrievable, and unusable. These containers are transferred intact for disposal by incineration (Daniels Heritage Environmental Services INC. 1250 Saint George St Unit 1. East Liverpool, OH 43920).