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WAKE FOREST BAPTIST MEDICAL CENTER
POLICY AND PROCEDURE BULLETIN
DEPARTMENT OF PHARMACY
PREPARED BY: Kathryn Bender, Pharm.D.
REVISED BY: Kathryn Bender, Pharm.D.
SUBJECT: Pharmacy Clinical Trials Service
I.
II.
POLICY:
The WFBMC Pharmacy Department will operate a Pharmacy Clinical Trials Service (PCTS) to
coordinate Pharmacy Department participation in clinical research of medications.
PURPOSE:
To provide administrative and distributive services which ensure safe research medication use
practices, accurately complies with specific protocol requirements as well as all local, state and
federal regulations.
III.
PROCEDURES:
A.
Control of clinical trial medication dispensing
1. All inpatient clinical trial medications are required to be dispensed by Pharmacy except
studies conducted in special procedures units (e.g. Cath Lab) where it is unfeasible
(due to the urgent need of these doses) to store and dispense clinical trial medications
and the plan for storage and preparation of medications are approved by the PCTS.
2. All outpatient clinical trials being conducted in the provider-based clinics for which
investigational medications will be dispensed to patients will have Pharmacy Clinical
Trials Service oversight regarding the storage, dispensing, labeling and distribution of
investigational medications.
B.
Clinical trial protocol review and study file
1. All clinical trial protocols which require Pharmacy services are forwarded to the PCTS
for review by the PCTS Coordinator.
a.
Each protocol is reviewed for determination of specific Pharmacy services
required.
b.
Each protocol is reviewed for feasibility, safety, accuracy and other
protocol-specific information. Any outstanding issues identified will be
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c.
discussed with the study principal investigator, study coordinator and or
study sponsor.
All subsequent amendments to the protocol will be forwarded to the PCTS
for review (as above) by the PCTS Coordinator.
2. Essential regulatory documents are obtained from the principal investigator, study
coordinator and/or sponsor for each clinical trial, and maintained in the PCTS studyspecific file.
a.
The following documents are obtained (or are available electronically) for
industry, individual investigator filing an IND, and government sponsored
studies:
(1).
IRB approval letter
(2).
FDA 1572 form
(3).
IRB-approved consent form
(4).
Investigator’s Drug Brochure (IDB)
(5).
Study protocol and all amendments
b.
The following documents are obtained for investigator-initiated non-IND
studies:
(1).
IRB approval letter
(2).
IRB-approved consent form
3. A study file containing study-specific documents for each clinical trial will be created
upon receipt of the protocol.
a.
b.
c.
d.
e.
C.
All essential documents will be maintained in the study-specific file (or
are stored electronically).
All correspondence regarding the clinical trial will be maintained in the
study-specific file.
All files are retained in the PCTS current or archive files indefinitely or
until written authorization from the sponsor to destroy the records is
acquired.
The binder contents will be incorporated into the study file when the file is
processed for archiving.
A database will be maintained of all current and archived files to enable
efficient retrieval of a file based on the name of the drug, sponsor,
principal investigator name and/or IRB approval number.
Pharmacy Procedure / Study Binder Development
1. Preliminary pharmacy procedures will be drafted by the PCTS Coordinator based on
available resources from the study sponsor and/or principal investigator.
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2. Procedures will be finalized after meeting with the study sponsor (initiation visit)
and/or principal investigator, receipt of sponsor pharmacy manual (if available) and/or
other pharmacy-related materials (e.g. IVRS users manual, etc.), and meeting with the
Pharmacy area liaison.
3. Pharmacy procedures will contain the following standard information (if applicable):
a.
b.
c.
d.
e.
f.
g.
h.
i.
j.
k.
Header: Protocol name, sponsor name, IRB number, principal investigator
name and contact numbers, study coordinator name and contact numbers,
study phase, Pharmacy area responsible, storage area for clinical trial
medication(s)
Study overview:
•Clinical trial phase
•Study design
•Treatment groups being studied
•Clinical trial medications- dose, route, frequency, duration of treatment
•How medications provided (from sponsor vs. from Pharmacy)
Physician order / Rx process
Randomization (if any) process
Clinical trial medication preparation process
Drug accountability process
Documentation on any other study-specific forms (if any)
Computer order entry process
Expiration date applicable to clinical trial medication(s)
Labeling process
Process for saving used clinical trial medication containers
4. A pre-printed physician order form will be developed by the PCTS Coordinator
(unless not applicable to the study) in collaboration with the study team.
a.
The order will contain the following standard information needed to order
the clinical trial medication:
•Study name / IRB number
•Patient name / MR number
•Patient-specific information necessary for randomizing patient / preparing
dose (e.g. randomization number, weight)
•Statement that patient is enrolled in the clinical trial
•Statement that patient signed an informed consent and a space to
document the date this was obtained
•Date / time dose due
•Stop date (if applicable)
•Pharmacy area / fax #
•Statement that order must be signed by an authorized prescriber only.
•Other study-specific information
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5. For non FDA-approved investigational drugs, a drug data sheet will be developed (if
not provided by the sponsor) which will summarize key information regarding the
drug:
a.
b.
c.
d.
e.
f.
g.
Pharmacology / Mechanism of action
Known adverse events
Dosing and administration
Precautions / special handling requirements
Monitoring guidelines (if any)
Compatibility with other medications (IV drugs)
Other information pertinent to the drug
6. Study-specific binders will be created by the PCTS for each study to be used by the
Pharmacy dispensing area designated to dispense the clinical trial medication(s). The
binders will contain the following study-specific documents/supplies:
a.
b.
c.
d.
e.
f.
g.
D.
Pharmacy procedures / example of pre-printed order
Randomization scheme (if applicable)
Drug accountability forms
Other documentation forms (if applicable)
Protocol
Drug data sheet(s)
Inservice log
Clinical Trial Medication Acquisition
1. Sponsor-provided clinical trial medications
a.
b.
c.
d.
e.
Shipment notification will be requested of the sponsor prior to the initial
and all subsequent shipments shipment of clinical trial medications/
supplies.
Upon arrival, the amount and integrity of the clinical trial medications /
supplies will be verified against the shipment invoice / packing slip
enclosed with the shipment.
Clinical trial medications will be immediately stored in a secure,
temperature-appropriate area of the PCTS or other designated area of the
Pharmacy.
Sponsor-specific documentation will be completed regarding the shipment
and instructions followed regarding notifying sponsor of the shipment
arrival. This documentation will be filed in the study-specific file or
binder.
Clinical trial medications / supplies will be documented as received on
appropriate sponsor-provided or PCTS drug accountability forms.
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f.
Clinical trial medications / supplies will be transferred to the designated
clinical trial storage area of the designated Pharmacy dispensing area prior
to study initiation.
2. Clinical trial medications purchased by the Pharmacy
a.
b.
c.
d.
e.
f.
E.
PCTS Coordinator or Technician will request the purchase of specific
items needed for a clinical trial from the Pharmacy Purchasing Agent.
Upon arrival, the amount and integrity of the clinical trial medications /
supplies will be verified against the shipment invoice / packing slip
enclosed with the shipment.
Clinical trial medications will be immediately stored in a secure,
temperature-appropriate area of the PCTS or other designated area of the
Pharmacy.
Invoices received from the wholesaler / manufacturer will be filed in the
study-specific file or binder.
Clinical trial medications / supplies will be documented as received on
PCTS drug accountability forms.
Bulk medication supplies will be repackaged (if necessary) according to
protocol-specific requirements for dispensing, and according to Pharmacy
Department policy regarding repackaging of medications, and transferred
to the designated clinical trial storage area of the designated Pharmacy
dispensing area prior to study initiation.
Pharmacist Inservices
1. An e-mail notification of inservice dates / times / location will be sent to all
pharmacists associated with the designated Pharmacy area.
2. All pharmacists associated with the designated Pharmacy area / shift(s) are required to
attend one inservice session for each study assigned to that area.
a.
b.
c.
Certain shifts may not be required to attend an inservice if determined to
be unnecessary due to the nature of a particular study.
Pharmacists who provide coverage in the designated Pharmacy area on an
occasional basis are not required to attend clinical trial inservices for that
area, however, they will not be permitted to dispense clinical trial
medications for these studies except in emergency situations. (see F.1.b.1
below)
Newly hired pharmacists who will have their primary practice in a
Pharmacy area designated for clinical trials will receive inservice training
on these studies during their orientation period.
3. An inservice log will be signed by each pharmacist attending a clinical trial inservice.
This log will be maintained in the study binder.
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F.
Clinical Trial Medication Dispensing
1. Inpatient Clinical Trials
a.
A pre-printed paper standard physician order form will be utilized by
authorized prescribers of a study to order clinical trial medication for
enrolled patients. The order must be signed by an authorized prescriber as
listed on the FDA 1572 form or designated by the principal investigator.
b.
Only the PCTS Coordinator and those pharmacists who have been in
serviced (“authorized”) on the procedures of a clinical trial may dispense
clinical trial medication(s) for this clinical trial.
(1).
In the event of an emergency, a pharmacist who has not been in
serviced (“unauthorized”) may dispense the clinical trial
medication in phone consultation with the PCTS Coordinator or
area liaison.
(2).
Authorized pharmacists for a particular study are those who have
signed the inservice log (located in the study binder) for that study.
c.
A study-specific computer code will be developed by the Pharmacy
Computer Support team to enable pharmacist order entry of a study
medication into the patient’s medication administration record.
(1).
A label will be demand or automatically printed for investigational
medication doses which are due. These will be affixed as specified
in the study-specific pharmacy procedures
(2).
Green auxiliary labels “For Drug Study Use Only” may also be
used if desirable / appropriate.
(3).
If sponsor-provided labels must be used, Pharmacy procedures will
specify how both labels are to be applied to each dose.
d.
All used clinical trial medication containers must be placed in a ziplock
bag labeled with subject initials/number and date/time of dose, and saved
according to the Pharmacy procedures.
2. Outpatient Clinical Trials (Dispensed Directly by PCTS)
a.
A pre-printed standard physician order form, study-specific order form,
and/or prescription will be utilized for authorized prescribers of a study to
order clinical trial medication for enrolled patients.
(1).
If a pre-printed standard physician order form is not used, evidence
of patient informed consent must be obtained before clinical trial
medication may be dispensed (i.e. copy of the signature page of the
consent).
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(2).
(3).
Order will be initialed and dated by dispensing pharmacist and will
be maintained in the study binder.
For outpatient clinical trials for which the only pharmacy services
provided are re-packaged medication(s) into ready-to-dispense
labeled containers for the study team to dispense, it is not
necessary to obtain individual patient order / prescription / consent
form as the Pharmacy is not functioning as a dispenser in these
cases.
b.
Only pharmacists who have been in serviced (“authorized”) on the
procedures of a clinical trial may dispense clinical trial medication(s) for
this clinical trial.
(1).
In the event of an emergency, a pharmacist who has not been in
serviced (“unauthorized”) may dispense the clinical trial
medication in phone consultation with the PCTS Coordinator or
area liaison.
(2).
Authorized pharmacists for a particular study include the PCTS
Coordinator and those who have signed the inservice log (located
in the study binder) for that study.
c.
A study-specific label will be utilized to label doses being dispensed.
(1).
For outpatient doses being administered in the clinic setting, a
study-specific computer code may be created (if appropriate- i.e.
usually for infusions being administered in the hospital CRU or
Day Hospital) for which a label will be demand printed, or a studyspecific label will be designed and laser-printed with the following
information:
•WFBMC PCTS header
•Name of study / IRB#/ Principal Investigator name
•Blank for patient name, date, subject number
•Unblinded studies: name of drug, dose
•Blinded studies: all possible drug names & doses / placebo
•Administration instructions (if any)
•Date / time dose due
•Expiration date / time (unless drug not repackaged)
•Blank for dispensing pharmacist initials
•Statement: For investigational use only
(2).
For outpatient doses being dispensed directly to the patient to be
administered in the home setting, the label will contain the
following information:
•WFBMC PCTS header (with address, phone number)
•Name of study / IRB#/ Principal Investigator name
•Blank for patient name, date, subject number
•Unblinded studies: name of drug, dose
•Blinded studies: all possible drug names & doses / placebo
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d.
•Directions for taking the medication
•Number of dosage units
•Expiration date (unless drug not repackaged)
•Blank for dispensing pharmacist initials
•Statement: non-FDA-approved drugs:“Limited by federal law to
investigational use only”- FDA-approved drugs: “For drug study
use only”
(3).
Green auxiliary labels “For Drug Study Use Only” may also be
used if desirable / appropriate.
(4).
If sponsor-provided labels must be used, Pharmacy procedures will
specify how both labels are to be applied to each dose.
All used clinical trial medication containers must be placed in a ziplock
bag labeled with subject initials/number and date/time of dose, and saved
according to the Pharmacy procedures.
4. For all studies dispensed by the Pharmacy Department, a hang sheet will be utilized to
document the date and time of preparation and transition of the study drug dose(s)
from the Pharmacy to the nursing unit.
G.
Preparation of Blinded Capsules
1. Empty gelatin capsules will be used to prepare blinded capsules for use in clinical
trials.
a.
b.
c.
The contents of the capsules will be dependent on the needs of the clinical
trial.
Solid tablets that will be over-encapsulated for blinding purposes will be
placed in an appropriate-sized empty gelatin capsule and back-filled with
Lactose Monohydrate or Methylcellulose Powder.
Placebo only capsules will be prepared with Lactose Monohydrate or
Methylcellulose Powder only, unless another inert substance is requested.
2. A capsule making machine will be utilized to prepare large quantities of blinded
capsules (i.e. > 50 capsules).
a.
b.
c.
H.
Smaller quantities can be manually separated and filled using a filler tray.
Gloves will be worn during the preparation process.
Prepared blinded capsules will expire one year from the preparation date,
or the date of the filler material, whichever comes first.
Central Drug Distribution
1. Clinical trial medications to be utilized in a multisite clinical trial may be prepared,
stored, and shipped to participating sites.
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a.
b.
c.
d.
Blinded capsules may be prepared by PCTS and shipped to study sites
upon request.
Clinical trial medications manufactured by another facility and shipped to
our site for storage and distribution to multiple sites will be housed in a
temperature-appropriate secure location.
Clinical trial sites will fax a drug reorder form to PCTS indicating the
quantity of study drug requested, and the date it will be needed.
Clinical trial sites will complete and sign the packing slip indicating the
quantity received and condition of shipment upon arrival. This will be
faxed to the PTCS.
2. The shipment carrier will be negotiated with the sponsor during the prestudy phase.
3. The PCTS will ensure that adequate supplies are maintained in storage to meet the
needs of the study.
I.
Disposition of CTMs for Return or Destruction
1. Industry-sponsored studies: The Pharmacy Clinical Trials Service (PCTS) Coordinator
will determine the sponsor's requested method for the final disposition of their CTMs
(both FDA-approved and investigational).
a.
Used primary containers of sponsor-provided CTMs (i.e. vials, premixed
bags, blisterpacks, etc.) will be saved for drug accountability unless directed
otherwise by specific written instructions by the sponsor.
(1)
Containers used for each dose prepared will be placed in a ziplock
bag and identified with pt. initials, date/time of preparation.
(2)
Containers not to be saved: broken glass ampules or other
containers which could pose a health hazard to the PCTS personnel.
Written approval not to save these containers must be obtained by
the sponsor prior to the commencement of the study.
b.
Once drug accountability has occurred and the sponsor has authorized
destruction of the containers:
(1)
Empty containers may be destroyed by placing them in an
appropriate waste receptacle (see c.2-c.3 below)
(2)
If the sponsor has not authorized destruction of the containers, they
will be maintained in a secure area of the PCTS until study close-out.
c.
At study close-out unused, expired or other CTMs for return / destruction
will be returned to the sponsor in accordance with protocol specifications
and/or sponsor instructions/ documentation. If it is undesirable or
inappropriate to return the CTMs to the sponsor, procedures for destroying
the medications on-site will be followed by the PCTS staff.
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(1).
Documentation that the sponsor authorizes on-site destruction of
the specific clinical trial medications must be obtained in writing
prior to the destruction.
(2).
Empty containers of non-hazardous CTMs (e.g. non- chemotherapy,
non-biological) will be disposed of via regular
waste.
(3).
Empty containers of hazardous CTMs will be disposed of in
accordance with the NCBH Pharmacy policy regarding handling /
disposal of hazardous agents (see intranet PPB-NCBH-PHARM-005
Chemotherapy (Cytotoxic Drugs): Sterile Compounding and Safe
Handling)
2. Non-industry-sponsored studies with FDA-approved medications: The disposition of
CTMs will be returned for credit, sent to another area of Pharmacy for use, or disposed
of on-site, unless otherwise directed in the protocol. The disposition will be determined
by the following:
a.
If the medication is purchased from the NCBH Pharmacy, and the
medication remains intact (i.e. not prepackaged into blinded capsules, not
cut in half, etc.) and in date, the medication will be transferred to the
Pharmacy Purchasing area for wholesaler return or use in another area of the
Dept.
b.
If the medication is purchased from the NCBH Pharmacy, and the
medication does not remain intact (i.e. contaminated, expired), then the
medication will be disposed of on site.
(1).
Non-hazardous clinical trial medications (e.g. non-chemotherapy,
non-biological) will be disposed of via off-site vendor contracted to
destroy medications for NCBH.
(2).
Hazardous agents: Chemotherapy, biological, and other agents
considered to be hazardous:
(a).
Handle and dispose of agents in accordance with the NCBH
Pharmacy policy regarding handling / disposal of hazardous
agents
(see
intranet
PPB-NCBH-PHARM-005
Chemotherapy (Cytotoxic Drugs): Sterile Compounding and
Safe Handling)
(b).
Document the disposal of these agents as outlined below.
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3. Document the return or disposal of each CTM dosage unit as follows:
a.
Industry-Sponsored studies:
(1)
(2)
b.
Non-Industry sponsored studies:
(1)
(2)
J.
Maintain study and sponsor-specific return / disposal completed
form in the study file.
If appropriate, document the return / destruction, and remaining
balance of “0” for each CTM on the study-specific drug
accountability form(s).
Document each medication to be destroyed on the study-specific
drug accountability form to be maintained in the study file.
If appropriate, document the return / destruction, and remaining
balance of “0” for each CTM on the study-specific drug
accountability form(s).
Sponsor Monitoring Visits
1. Sponsor site inspection, monitoring, and close-out visits will be scheduled with the
PCTS Coordinator in advance.
2. The PCTS Coordinator and/or Technician will accompany the sponsor monitor during
the entire visit with the PCTS. All outstanding issues identified by the monitor will
be resolved as soon as possible.
Effective Date: May 2002
Revision Dates: 06/04; 08/05; 11/08; 9/11
Last Reviewed: 03/04; 06/04; 08/05; 11/08; 9/11
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