Department of Pharmacy Policies & Procedures

Number: 5:16

Effective Date: October, 1987

Revisions: 4/99; 4/00; 3/05; 9/08

Reviewed: 9/09

Approval:

Subject: INVESTIGATIONAL DRUGS

PURPOSE

The purpose of this policy is to define the responsibilities of the Pharmacy and its role in handling investigational drugs at UAMS Medical Center.

POLICY

The UAMS Department of Pharmacy shall have oversight for the storage and use of any investigational drug used in human research or studied at UAMS Medical Center.  All sponsors of studies, principal investigators and/or key research staff having contact with investigational drug studies at UAMS, will consult with the Department of Pharmacy during contract arrangements for the study, to review aspects required for study drug handling.  The Pharmacy will review and discuss the following:  drug storage requirements, dispensing requirements, recordkeeping procedures, unused drug return and financial requirements.  Any investigational drug used and handled must have received protocol approval for study from the UAMS Institutional Review Board.  The UAMS Pharmacy will refer to the Code of Federal Regulations for 21 CFR 312 – Investigational New Drug Applications and 21 CFR 314 - Applications for FDA Approval to Market New Drugs for issues not referred to in this policy.

If the Pharmacy does not store the drug but it is managed by the investigator, an agreement will be given to the Pharmacy outlining the responsibilities that the investigator will assume.  If a study is blinded, the Pharmacy shall not release any information about drug identity unless authorized by the study sponsor. 

 A.    General Responsibilities of the Pharmacy Department 

1. The Pharmacy will provide an official contact person for the sponsor and/or investigator to work with while making contract arrangements and when making periodic audits of the clinical investigation.
2. The Pharmacy will maintain accurate records of all drug use for studies in which the drug is actually stored in the Pharmacy.
3. All Pharmacy personnel involved with the study will be given education on the study and its requirements and restrictions for proper dispensing.  Training records will be kept by the Research Pharmacy.
4. In the event that the study involves both inpatients and outpatients, the Pharmacy will decide which area of the department will store the drug and inventory will be transferred to other areas in a standardized manner to maintain an accurate accountability of study product.
5. The Pharmacy will assure that all investigational drugs bear the appropriate investigational drug labeling at dispensing.

B.   General Requirements for Sponsors and Investigators 

1. The Pharmacy must receive a copy of the UAMS IRB approval letter for each approved protocol prior to receiving investigational drug supply.
2. The Pharmacy must receive a copy of the contract/clinical trial agreement, the UAMS IRB approved protocol (study plan) for the study, a copy of the investigator’s brochure, documentation of approved investigators and/or sub investigators for each study, copy of form 1572, and identification of key study staff designated by the investigator to communicate with the Pharmacy, along with the name and contact information for the sponsor.   All of the documents listed will be available in UAMS Crimson study budgeting system at time of Pharmacy study review.
3. The sponsor and/or investigator must provide any pertinent documentation regarding the drug, specifically a copy of the FDA IND acknowledgement letter (if IND required for study), and FDA requirements for storage, shipping and handling of the drug. 
4. The Pharmacy must receive a copy of the informed consent signed by the subject (or have electronic access) before drug can be prepared and dispensed.
5. All investigational drugs on inpatients will be ordered via Sunrise computer system.  Investigational drugs dispensed to outpatients require a prescription and/or documentation in the patient record by study staff listed on form 1572 that have appropriate prescribing privileges.  A verbal order from study staff personnel is not an acceptable study drug order.  The prescription or drug order must be complete and accurate, when sent to the Pharmacy.  Investigational protocol number or identification (or IRB number) must be on all investigational drug orders, to assure correct dispensing.  If the study drug is an FDA approved drug and is supplied, then the study drug order must state “dispense from investigational drug supply”.
6. If drug study involves randomization to different treatments or drugs, the prescription or physician order must state clearly randomization information, to assure proper dispensing.
7. Pharmacy will be contacted by investigator or designee regarding any meetings on the study.  All study monitor visits to Pharmacy must be scheduled with Research Pharmacy personnel. 
8. Pharmacy has controlled access and all personnel visiting Pharmacy areas (study personnel, investigator, monitors) must sign “visitors log” upon each visit, and state purpose of visit.
9. The investigator will maintain records of subjects placed on the study which should mirror the information recorded in the Pharmacy.
10. The investigator will notify the Pharmacy and all related study personnel any time a study is suspended, terminated or closed or anytime a subject is removed from a study.

 C.  ADDITIONAL REQUIREMENTS OF INVESTIGATORS RELATED TO SPECIAL STUDY TYPES

1. Industry Sponsored Study

The principal investigator will provide the Pharmacy with:

1. A synopsis of the study, drug accountability requirements, and nurse information sheet.
2. A study contact person for Pharmacy issues

2. Investigator is the Sponsor:

a.       The investigator must have a written agreement with the Pharmacy that specifically states the sponsor arrangement, and defines the responsibilities of the Pharmacy, the investigators and the study staff for handling and documentation of investigational drugs.

b.      He/she must provide drug information which can be furnished to patient care areas

c.       If investigator and Industry are co-sponsors, investigator must provide information to the Pharmacy on the authority/responsibilities of each party involved in conducting the study.

 D.    STORAGE AND DISPENSING OF DRUG

1. The drug will be stored under proper conditions according to protocol and drug information provided.
2. The drugs will be stored separately by protocol.
3. The location of the drug storage may vary according to the requirements of the study.
   1. If the study drug is to be administered by a nurse

§         The Pharmacist will enter study drug prescription or physician’s order into the Pharmacy computer.  Two Pharmacists will check the order and label for accuracy.  For chemotherapy studies, BSA will be checked to assure study dosing is calculated correctly.

§         Pharmacy will store and dispense all products.

§         Dispensing records will be maintained accurately and completely, and in accordance with the protocol requirements.

§         Any manipulation of the drug will be performed per protocol in an acceptable manner.  The dosage form of an investigational drug will not be altered outside of the protocol.

§         Two Pharmacists will check final prepared study drug.

§         Pharmacy will not keep used vials or ampules of any investigational products.  All investigational drugs will be considered as biohazardous waste and will be destroyed per pharmacy protocol.

§         Pharmacy will not keep used and/or returned IV bags or used tubing/tubing filters.

2. If the study drug is to be self-administered by the patient

§         The investigator may arrange to store the drug outside the Pharmacy and maintain records of dispensing after furnishing the Pharmacy a signed form accepting the responsibilities of drug storage and control.

§         The Pharmacist will enter study drug prescription or physician’s order into the Pharmacy computer.  Two Pharmacists will check the order and label for accuracy.

§         The drug must have appropriate labeling.  All self-administered drug must have on label “for investigational use only”.

§         Two Pharmacists will check prescription before dispensing to a subject.

§         All investigational drug prescriptions can be dispensed by a Pharmacist or Physician, directly to the subject.  Pharmacy cannot mail study medication to subjects.  Exception would be if study drug has too short an expiration date to fill complete prescription (ex. Biological agent, like alpha interferon), and approval for mailing would have to come from study sponsor and/or the FDA.

§         Any drug returned by the subject will be the responsibility of the investigator and must have accurate records of waste/return and any disposal of the product.

3. If the study drug or treatment requires administration only by the investigator

§         The drug or treatment may be stored in a mutually acceptable location, but the drug must be stored in a secure location that meets drug storage requirements.  If storage is outside the Pharmacy, a signed form will be furnished to the Pharmacy accepting responsibility for the drug and must meet other duties as outlined in section b above.

4. If investigational drugs from a non-UAMS study are required for a patient, the ordering physician must furnish a copy of the informed consent and the protocol to the pharmacy.  A form 1572 must be completed.  Study drug information must be available for the nurses giving care to the patient.
5. If the investigational study is to be conducted at the UAMS GCRC (located on VA property), the VA pharmacy must be contacted, regarding drug dispensing.
6. If the drug requires special storage and handling, any unusual storage equipment must be furnished by the sponsor or provision must be made financially for UAMS to obtain the equipment.
7. If an investigational drug presents a health hazard to the healthcare personnel or the general population, storage, preparation, dispensing and disposal shall be presented and approved by the Campus Biohazard Safety committee before it may be used.
8. Controlled substances will be stored in the pharmacy and will meet all requirements of the policies for managing controlled substances.

E.    RECORDS OF USE

1. National Cancer Institute (NCI) studies where drug is supplied through the Cancer Therapy Evaluation (CTEP) or the Pharmaceutical Management Branch of NCI (PMB) will be recorded on Drug Accountability Forms (DARFs) according to the requirements in the NCI Investigator’s Handbook and the Publication “Monitoring of Clinical Trials, Section 5.3.1”.  NCI accountability form is the preferred DARF for all cancer studies, unless sponsor requires different dispensing documentation.  On other studies at UAMS, accountability logs provided by the sponsor will be used if required.
2. There will be a separate accountability log for each drug, strength and/or dosage form in each protocol.
3. The accountability sheet will be accurately completed
   • Each line will be completed for all spaces,
   • Any unusual entry will have an explanation fully written out in the space below the entry (i.e. Broken vials, transfers between pharmacy dispensing areas),
   • There will be an interpretation of all personnel initials provided and maintained in a log book,
   • All corrections will be performed by placing one line through the error, then initialing and dating the error.  No erasures or White Out^R may be used on the official dispensing logs.  Only blue or black ink will be used on dispensing logs.
4. A copy of the records shall be released to the investigator and/or the sponsor at the close of the study.  For controlled substances, records will be retained for 2 years per DEA requirements.
    

F.     DISPOSAL OF DRUG

1.      Any returned, unopened, or undispensed drug will be returned to the sponsor of the research or may be disposed of on-site if instructions for disposal are available from the sponsor/principal investigator or as outlined in the study protocol.

2.      Partially used containers and emptied containers will be treated as biohazards.  To protect employees from undue exposure to biohazardous wastes, partial vials and emptied containers (vials) will not be saved by the Pharmacy for study sponsor(s) to view; all will be destroyed after drug preparation is completed.

3.   Drugs considered hazardous include those that exhibit one or more of the following six characteristics in humans or animals:

Ø  Carcinogenicity

Ø  Teratogenicity or other developmental toxicity

Ø  Reproductive toxicity

Ø  Organ toxicity at low doses

Ø  Genotoxicity

Ø  Structure and toxicity profiles of new drugs that mimic existing drugs determined hazardous by the above criteria.

4.   Investigational drugs should not be disposed of in regular waste containers or in the city waste water unless there is certification from the sponsor that the drug is safe for humans.

5.   Disposal of any drug and the method of disposal will be recorded on the drug accountability form.

6.      Controlled substances will be handled, according to DEA rules, see controlled substances policy.

G.    EXPORT AND TRANSFER OF INVESTIGATIONAL DRUGS

1. Drugs may be imported for use on a patient if the consignee is a qualified investigator named in the IND and the protocol has been approved by the UAMS IRB.
2. If a study drug is to be used between several different investigative sites, drug may only be transferred between sites according to instructions in the original protocol.  Any site where drug is transferred must be listed on the FDA form 1572.  Drug must be delivered to the site and may not be reshipped.  If transfer is not covered, the sponsor must furnish written authorization in the form of a 1572 to the transferring site.  This authorization will be kept with original invoices and a record of the transfer will be made on the Accountability Log.  It is the responsibility of the receiving site to maintain and accountability log on all drugs received.