Investigational Drug Service (IDS) Forms
The policy below affects only UPHS hospitals and affiliated CPUP practices. It is undergoing major revisions as of October 2009. A new version of this policy will be posted once it has completed review and approval by the necessary UPHS committees. Other schools on the Penn campus, as well as clinical practices not part of CPUP, may be covered by other policies instead of this one.
Investigational drugs will be procured, stored, inventoried, dispensed and used through the Investigational Drug Service (IDS) in full compliance with regulations or requirements of the FDA, JCAHO, ASHP, Federal and State Boards of Pharmacy, other applicable organizations and in accordance with applicable Hospital, School of Medicine, and University policies and guidelines.
To establish procedures for the proper control, storage, use and handling of investigational drugs. SCOPE: This policy applies to all personnel involved in the handling of investigational drugs intended for administration to Hospital inpatients and to outpatients treated in the various clinics which are part of the UPENN entity. This policy does not provide for control over the use of radiopharmaceuticals or medical devices.
(1) "Investigational Drugs", in accordance with FDA regulations, are those new drugs for which an IND has been filed which are exempt from pre-marketing approval requirements and may be lawfully shipped for used in clinical investigations in human subjects. (2) A drug that is lawfully marketed in the U.S. may still be considered investigational and require that an IND be filed if the proposed use of such an agent involves a controlled study aimed towards seeking a significant change in the labeling, advertising, route of administration, dosage level, or other factor that affects the risks associated with use of the product. (3) Drugs which are not on the Hospital Formulary and are to be dispensed within the context of research protocols will also be considered "investigational" and will not require that a Non-Formulary Request Form be filed with the department of Pharmacy Services provided that pre-arrangements with the Pharmacy IDS have been made.
FDA: U.S. Food and Drug Administration
IDS: Investigational Drug Service
IRB: Institutional Review Board
JCAHO: Joint Commission for the Accreditation of Healthcare Organizations
PI: Principal Investigator
- The Institute for Translational Medicine and Therapeutics (ITMAT) will establish an Investigational Drug Service (IDS) to implement and to monitor the effectiveness of this policy within the Medical Center. A pharmacist will be appointed to organize and oversee activities relating to this investigational drug policy. Distribution, accountability and monitoring of research protocol drugs by others, including clinical pharmacist specialists or other specially trained individuals within research-orientated departments and specialties will be performed as part of the IDS.
- The Pharmacy and Therapeutics Committee will monitor the implementation and operational effectiveness of this policy on behalf of the Medical Staff.
- The Office of the Vice Dean for Research and the Chairman of the Pharmacy and Therapeutics Committee will be notified of non-compliance with this policy. Actions taken will be in accordance with Hospital and University policies.
- All investigational drug protocols must be approved by the IRB.
- Drugs intended for use in inpatients of the Hospital will be distributed through the established inpatient pharmacy drug distribution system.
- Investigational drugs dispensed to Medical Center outpatients will be distributed from one of the following areas:
- HUP Outpatient Pharmacy
- Oncology Outpatient Pharmacy
- Investigational Drug Service
- Satellite area designated by and under the direct supervision of the IDS
- Investigational drug use in Medical Center outpatients may be exempt from the pharmacy handling requirement provided that:
- The IDS has received a copy of the current protocol.
- The PI can provide adequate storage and control over the distribution of investigational drug supplies as outlined in Appendix A: Medical Center Standards for Handling Investigational Drugs.
- The use of investigational drugs in hospital inpatients and in Medical Center outpatients will be reviewed by the Pharmacy and Therapeutics Committee.
- Investigator's Responsibility for each research protocol:
- a. Prior to the initiation of a protocol which involves the use of an investigational drug in a human being, the investigator must have received approval from the University's Office of Research Administration, Committee on Studies involving Human Beings.
- b. The PI will contact a pharmacist representing the IDS to arrange for storage, inventory, packaging, labeling and dispensing of all investigational drugs to hospital inpatients through the established pharmacy drug distribution system. Investigational drug dispensing to hospital inpatients through means other than the established pharmacy systems may be acceptable, but NOT without the approval by the Pharmacy and Therapeutics Committee or by the pharmacist representing the IDS. Investigators seeking a special exemption to this policy must submit a written request to the Chairperson of the P & T Committee or to the IDS pharmacist, outlining in detail the reason for the requested exemption. If allowed, this provision does not exempt the PI from providing the Department of Pharmacy Services with the documents mentioned in (6E), nor does it exempt him/her from the responsibilities outlined in (6F).
- c. Operational costs associated with the IDS must be planned for in initial stages of protocol development. Before submitting a final budget to a sponsoring agency, investigators should contact a pharmacist representing the IDS to determine what funds are needed for pharmacy services. The source and/or type of research funding will ultimately determine the mechanism the investigators use to provide reimbursement for pharmacy-related costs. The IDS will not provide service without the appropriate reimbursement to support their services.
- d. The PI or his/her authorized designee with notify the appropriate Head Nurse and Nursing Clinical Director if patient care will be other than that usually delivered in a general care unit. If the patient will require special monitoring, such as telemetry, or more frequent observations by nursing staff, this needs to be planned for as a programmatic requirement.
- e. The PI will forward a copy of the complete investigational protocol including the Protocol Face Sheet as submitted to the IRB, to the pharmacist representing the IDS.
- f. The PI or authorized co-investigator is responsible for obtaining written, informed consent from each patient prior to the use of an investigational drug. The PI or authorized designee will document in the patient's medical record that informed consent has been obtained.
- g. Each order for an investigational drug intended for an inpatient must be placed in accordance with current medication prescribing policies as outlined in the current Hospital of the University of Pennsylvania Formulary. To prevent any misinterpretation, investigators must explicitly write the words "STUDY DRUG" and, whenever possible, a protocol number (assigned by the IRB or a cancer collective group) adjacent to the drug name. It is strongly recommended that the PI contact a pharmacist representing the IDS to resolve questions regarding the format for written orders or prescriptions for investigational drugs.
- h. Investigators may order investigational drugs for outpatients with a written prescription following the format outlined in 6G. The investigator may verbally communicate the prescription to a pharmacist who will immediately reduce the prescription to writing. Controlled substances will require a written prescription before dispensing except in emergency situations as specified in federal and state regulations.
- ITMAT has established an Investigational Drug Service (IDS) whose charge is to provide safe and responsible handling of investigational drugs. The purpose of the IDS is to maintain control and accountability of investigational drug use in the Medical Center to promote maximum benefit and safety for patients enrolled in studies. This service is not designed nor intended to impinge upon the rights or activities of the investigators. Rather, it is intended to provide assistance and support in conducting studies, while adhering to Medical Center policies.
- a. All investigational drugs maintained by the IDS will be accounted for in such a way that every transaction involving the receipt or dispensing or other manipulation of such drugs can be clearly identified as to date, recorder, research subject when applicable, quantity and balance on-hand.
- b. The pharmacist representing the IDS will prepare written dispensing instructions for each protocol (except for single-patient treatment protocols approved by the IRB in urgent situations) to be followed by Pharmacy staff when dispensing investigational drugs. These instructions will explain patient enrollment, drug dosing and preparation, dispensing and accountability.
- c. All investigational drugs dispensed by the inpatient and outpatient Pharmacy will be integrated into their respective drug distribution systems with respect to packaging, labeling, order review, drug profile, maintenance and drug delivery. In addition, investigational drug labels will be used to distinguish them from other drugs by the additional legend "Caution - New Drug, Limited by Federal Law to Investigational Use" (or equivalent).
- d. The pharmacist representing the IDS will return unused or expired investigational drugs to the PI or sponsor unless permitted in writing to destroy the drugs.
- e. The pharmacist representing the IDS will review investigational drug usage on a routine basis and order new supplies from the sponsor, on behalf of the PI, when necessary.
- f. The pharmacist representing the IDS, in conjunction with the PI, will prepare an Investigational Drug Data Sheet (IDDS) for all non-FDA-approved research drugs intended for administration to hospital inpatients. This information is needed to assure proper understanding of the administration and monitoring of the investigational drug by all personnel involved with its use.
- g. The pharmacist dispensing the investigational drug to a hospital inpatient will provide the patient-care unit with a copy of the IDDS in order to provide the necessary information about the drug to the Nursing Staff prior to drug administration. The pharmacist representing the IDS will also send a copy of the completed Investigational Drug Data Sheet to the appropriate Head Nurse.
- h. The pharmacist representing the IDS will inform the Pharmacy and Therapeutics Committee about investigational drug use periodically at regularly scheduled meetings. The Committee, Hospital Administration, and the Vice Dean of Research will be provided with an annual summary of investigational drug use, including but not limited to the number of drug studies in progress, a listing of all drugs studied during the previous year and a summary of adverse drug experiences.
- i. Operational costs associated with the IDS must be planned for in the initial stages of protocol development. These costs are the responsibility of the Investigator and budgetary arrangements should be mutually agreed upon by the PI and the pharmacist representing the IDS. The IDS pharmacist can provide the PI with a written assessment of the Pharmacy costs associated with a drug study (Investigational Drug Service Cost Analysis) prior to study initiation so that these costs may be incorporated into the budget submitted to the prospective sponsor. Additional information may be found in Section 6C above. IRB approval will only be granted to research protocols which are in conformance with this Medical Center Policy. The IRB will require that the IDS be notified of studies which plan to use investigational drugs. The IDS will be considered notified if the PI forwards a copy of a research protocol to the IDS or if a pharmacist is present at study planning or protocol review sessions other than the IRB.
STANDARDS FOR HANDLING INVESTIGATIONAL DRUGS
IRB Approval: All research intended for use in human beings must be approved by the Institutional Review Board (IRB) prior to their use. Consult the IRB document entitled "Guidelines for the Preparation of Protocols for Review".
Informed Consent: The Principal Investigator (PI) or authorized co-investigator is responsible for obtaining the written, informed consent from each patient prior to the use of an investigational drug. The PI and his/her designee will document that informed consent has been obtained.
Storage and Distribution:
All investigational drugs intended for use in hospital inpatients are to be stored in the Department of Pharmacy Services and their distribution incorporated into the regular pharmacy distribution system. Contact the pharmacist representing the IDS to arrange for investigational drug distribution and for further information. Investigational drug use in Medical Center outpatient clinics may be exempt from the pharmacy distribution requirement if: (1) the IDS has received a copy of the protocol and (2) the investigator can provide adequate storage and control over the distribution of investigational drug supplies as outlined below.
Drug and Protocol Information:
Protocols and inventory/distribution records pertaining to investigational drugs distributed by the Department of Pharmacy Services will be maintained by the IDS. Investigational Drug Data Sheets will be prepared by the IDS for drugs which are not commercially available and will be administered to inpatients in research protocols. These sheets will be available in the pharmacy and on the nursing unit where the investigational drug is administered. This document contains information regarding the administration, pharmacokinetics, known toxicities, interactions and other information known about the drug. The information will be reviewed at regularly scheduled meetings of the Pharmacy and Therapeutics Committee.
Adverse Drug Reaction Reporting:
If any unexpected adverse reaction or complication develops during the course of their research project, the investigator must notify the Associate Director of Regulatory Affairs immediately, followed by a written report to the IRB within ten days of the event. All unexpected adverse drug reactions are also to be reported to the Department of Pharmacy Services as outlined in the University of Pennsylvania Medical Center's "Formulary of Accepted Drugs" (page xiv).
EMERGENCY AND TREATMENT USE OF INVESTIGATIONAL DRUGS
Investigators should notify the Pharmacy that an emergency investigational drug is to be used and provide the following information: investigator's name, patient name, test-agent name and IND #, sponsor, and a phone number where investigator may be reached. Investigators should consult Appendix E of the IRB Guidelines for details pertaining to the use of test agents in emergencies.
Investigators conducting outpatient studies who choose not to utilize the IDS for drug control and distribution must demonstrate compliance with JCAHO, FDA, State and Local requirements for drug control. Investigators are required to:
- Ensure proper labeling for outpatient use. Elements of a proper label include: Patient name and study number (when applicable), date dispensed, drug and/or study name (e.g."_______ Study Drug") number of doses per container, investigator name, hospital name and/or clinic name and the statement "New Drug: Limited by Federal Law to Investigational Use"
- Maintain current and adequate records of the distribution of all drug supplies including dates, quantities and use by subject.
- Maintain adequate drug supplies and store in a securely locked, well-constructed, limited access storage area. Comply with Drug Enforcement Administration (DEA) regulations for controlled drugs.
- Provide protocol and drug information including pharmacology, kinetics, side effects, dosage forms, administration information or other pertinent data to the IDS.
- Disseminate pertinent drug information to all personnel involved with the dispensing or administration of the investigational drug.
- Comply with FDA regulations for information disclosure and return of used drug supplies at study termination.
- If a research subject is admitted to HUP, notify the pharmacist representing the IDS if protocol drug treatment is to continue.