Pharmacy Investigational Drug Services for Clinical Research

Pharmacy Investigational Drug Services for Clinical Research Jennifer Colon, PharmD, MS, MBA Pharmacy Clinical Specialist-Investigational Drug Services Temple University Hospital Adjunct Clinical Professor-Temple University School of Pharmacy

Objectives Learn about services provided by Investigational Drug Services (IDS) Pharmacy Understand how using the IDS Pharmacy can assist and enhance research Gain further understanding of operations within the IDS pharmacy

Pharmacy Locations Inpatient Pharmacy/Pharmacy Administration/Research Pharmacy; Rock Pavilion Zone B, Basement Inpatient Pharmacy Satellite; Boyer 3 rd Floor Outpatient Cancer Center Pharmacy; 4 th Floor ACC Building Outpatient Pharmacy; 1 st Floor Parkinson s Pavilion

IDS Operations Pharmacy Clinical Specialist (Jen Colon) Back Up Pharmacist Regular Operations (Outpatient Studies) Monday through Friday 7:30am 4pm Inpatient Studies 24 hour service through Inpatient Pharmacy (2-8280) On call and special arrangements (Jen)

Investigational Drug Definition Agent being considered for commercial marketing, not yet approved by the FDA Approved medication being studied for an unlabeled use or population Investigational drugs can be: new drugs or old drugs with: new indications; new combinations; or new components; or investigational use of commercially available drugs

Purpose of the IDS Pharmacy To ensure research involving investigational medicine is conducted appropriately, maximizing patient safety Provide additional support to study teams related to research (randomization, drug accountability and disposition, blinding/unblinding)

Regulatory Compliance The IDS pharmacy assures compliance with all federal (FDA, NIH, NCI), state, JCAHO, and IRB regulations concerning investigational medication. The IDS pharmacy also assures compliance with TUHS administrative/nursing/pharmacy policies The IDS Pharmacy assures compliance with USP 797 & 795 guidelines

Regulations & Drug Research State of Pennsylvania Dispensing (any legend drugs, including investigational drugs) is limited to a licensed pharmacist, physician, or dentist Pharmacy practice act governs requirements for labeling, documentation of medication dispensing Investigational drugs for inpatient administration must be stored and dispensed from the hospital pharmacy

FDA Requirements-Investigational Drug Storage Secure location with limited access Storage conditions according to instructions on drug label or in accordance with the protocol (temperature, humidity, light, min/max temps) Investigator Responsibilities 21 CFR 312.61 Administer drug only to subjects under personal supervision of primary investigator or sub-i. Access to the drug is limited and not supplied to those not authorized to receive it.

Joint Commission Requirements MM.7.40-Investigational medications are safely controlled and administered Pharmacy is responsible for the storage, dispensing, labeling, and distribution of investigational medications. Investigational Drug Data Sheet (IDDS) describing therapeutic indications, AEs, drugdrug interactions, and contraindications must be part of the permanent medical record

Investigational Drug Service Basic Activities: Registration of drug s use in hospital Procurement (ordering, returns, inventory management) Storage Preparing/packaging Dispensing Provision of drug information Maintenance of records

Compounding and Packaging

Packaging-Euclid

Packaging-Euclid

Packaging-Blister Packs

Investigational Drug Service Administrative Responsibilities Reordering investigational drugs* Disposal of used or unused drug in accordance with sponsor s protocol and hospital policy (TUH-ADMIN-930(1).801)* Preparing and maintaining pharmacy binders for each protocol Preparing budget proposals for pharmacy charges for each protocol Billing for IDS services *at the discretion of the primary investigator and study team

Investigational Drug Service Administrative Responsibilities IRB Membership at Temple University and Fox Chase Cancer Center Protocol management Staff development and in-servicing education Providing guidance related to compounding and handling of hazardous medications (biologics, chemotherapy, human tissue) Providing tours for site qualification and accommodating all site visits

A Quick Tour.. Temple University Hospital Inpatient Pharmacy holds some of the most advanced pharmacy technology in the region. Using these systems helps ensure patient safety and drug delivery efficacy and accuracy. Investigational drugs are stored according to CFR 312.69 which mandates all investigational drugs must be stored in a securely locked, substantially constructed enclosure, with limited access to prevent theft or diversion

Advanced Technology-Talyst

Advanced Technology-Intelifil

Room Temperature Storage

Room Temperature Storage

Refrigerated Storage

Narcotic Vault

Narcotic Vault

-20 Degree Freezer

Sterile Compounding Room-Positive Pressure Hood

Sterile Compounding Room-Positive Pressure Hood

Cancer Center Pharmacy-Negative Pressure Hood

Cancer Center Pharmacy-Negative Pressure Hood

Cancer Center Pharmacy-Positive Pressure Hood

Cancer Center Pharmacy- Refrigerated Storage

Investigational Drug Service Research and Development Activities: Protocol development-especially drug delivery and monitoring Act as unblinded personnel in single and double blind studies (Pharmacy will break the blind if needed) Randomization (if requested) Pharmaceutical research (formulation & development) Preparation of dosage forms Drug analysis & quality control

IDS Pharmacy Services Initial protocol review Access pharmacy s ability to accommodate the protocol (biologic, human tissue, virus) Participate in site qualification, pre-study, monitor visits, and audits Study budgeting for drugs and pharmacy services Pharmacy procedure and IDDS (Investigational drug data sheet) development

IDS Pharmacy Services Store, dispense, & account for study medications from initial sponsor shipment through final drug return or destruction Support of investigator initiated projects (study design, randomization, blinding, accountability log development, preparation of double-blind drug and placebos, and patient monitoring) Maintenance of discontinued study documents

When is the IDS Pharmacy Required to be Involved? Pharmacy must dispense any inpatient administered investigational medication. Any medication requiring preparation or manipulation of any kind (USP 797 & 795 guidelines) for both outpatient and inpatient studies Any medication requiring repackaging or relabeling (USP 795 guidelines) Any premixed intravenous infusion administered inpatient or outpatient. Compounding of placebo match

Exceptions at TUHS Prepackaged oral medications (pills, inhalers) or topical agents for outpatient protocols can be stored in primary investigators department. Medication must be stored in a temperature controlled, locked area of the department with limited access.

What Does Pharmacy Need from the Study Team? IRB and contract approval before study can be opened for dispensing All study materials must be supplied to the pharmacy prior to initiating a study A time period of 6 weeks notice is requested to ensure staff is trained, as appropriate Ensure an IDDS sheet is provided to pharmacy and placed in each inpatient s chart

Initiating IDS Services Review of draft protocol or grant IDS cost proposal (usually requested by Arleen Wallen for sponsored projects as part of protocol budget) Access legal requirements and any special needs Evaluate ability to conduct study Ensure that pharmacy fees are included in research contract or grant

Requirements Prior to First Dispensing Drug must be onsite Final protocol and investigator s brochure (electronic copies are acceptable) Pharmacy binder or all documents needed to make one (accountability logs, destruction logs, specific temp logs) Notice of IRB approval-irb number (all studies must be approved by the IRB) Grant/study specific account numbers (FOAPAL)

I m Ready to Enroll a Patient.How Do I Order an Investigational Drug?

Required Medication Order Contents-Inpatient Order Must be entered into MIS/TDS by a physician on the study team as a non formulary type in to prevent insurance from being charged Study name and IRB number must be included in the order Active agent vs. placebo (if blinded) Drug name, dose, route, frequency of administration, quantity, or duration Order states that This drug is for investigational use only Pharmacy will provide you with a summary of how to enter an order for each study

Required Medication Order Contents-Outpatient Order A written order or BUMPO (Back up medication physician order) must be submitted to the IDS pharmacist prior to dispensing. Drug study name and IRB number Allergies Patient medical record number Drug name, dose, route, and frequency of administration Quantity or duration Primary investigator signature Date and time the medication is needed

This Sounds too Good to be Free How Much Do You Charge for IDS Services?

Pharmacy Charges Prior to initiation of any protocol an IDS budget estimate will be provided to the study team and the Clinical Trials Office Each protocol will be invoiced quarterly as appropriate for pharmacy services

Pharmacy Charges Development of Dispensing Protocol and Procedures $1,500 Patient Randomization Maintain Drug Inventories Unit-dose Oral or Topical Unit-dose Injection Intravenous Infusion Parenteral Nutrition Antineoplastic Agent Compounded or Packaged Doses Outpatient Dispensing Fee $10/patient $20/month $5/dose $10/dose $15/dose $30/dose $50/dose $40/hour $10/drug Termination of Investigational Study $500

How Much Notice is Needed for Site Visits? Monitoring visits/site qualification visits/closure visits-please allow 2 weeks advanced notice to ensure pharmacy can accommodate the visit.

Frequently Asked Questions.

How Do We Deal With Research that Involves Commercial Product? Sometimes commercially available drug will be supplied by the sponsor. If it is not it is ordered by pharmacy and stored separately from regular stock. We do not use regular pharmacy stock for investigational purposes All investigational drugs are stored separately from regular stock Once the study closes, the drug is destroyed.

Do We Mark Up the Price of Medication Acquired for Research? All medication purchased by pharmacy for investigator initiated and federally funded research (NIH, NCI) is provided to the investigator at cost. All medication purchased by pharmacy for a sponsored study is marked up by 30%

Why Can t We Reuse Medication Returned to the Pharmacy? Per FDA guidelines and state regulations we can not reuse medications once they are dispensed for patient safety. Storage conditions outside of the pharmacy may allow for loss of integrity. We would no longer have assurance of strength, quality, purity, or identity of the drug. The pharmacist or doctor dispensing a drug is legally responsible for all hazards or contaminations that may arise if they return dispensed drug back into regular stock

How Are Temperatures Monitored At TUH? Room temperature-daily manual recorded temps Investigational refrigerators-daily manual recorded temps -20 Freezer-daily electronic recording via a temperature recording disk All devices are alarmed and the manager on call and maintenance are notified if a deviation occurs

What is Used to Make Matching Placebo Oral? Our most common compounding procedure is to fill an empty gelatin capsule with an inert substance (lactose monohydrate or starch) We utilize an opaque capsule to maintain the blind. Our capsules come from Medisca, Inc. Placebo tablets can be manufactured by our GMP lab at the School of Pharmacy (separate entity from TUH Pharmacy)

How Do Blind Active Medication if it has a Matching Placebo? We ensure both active and placebo medication look (and weigh in the case of capsules) identical prior to packaging or dispensing. For an injectable agent an opaque sleeve may be placed over a bag or syringe if coloring of each agent varies The compound (active/placebo) is documented and a lot number is assigned to differentiate when packaging

How Do We Dispose of Investigational Medication? If the investigational drug is a proprietary agent the sponsor usually takes accountability for it upon expiration or study closure Chemotherapy is deidentified and disposed of in yellow chemo waste containers contracted to Stericycle for destruction Investigational medication is deidentified and disposed of in Red Biohazard trash also contracted to Stericycle for destruction

How Long are Binders and Study Records Stored? After one year of on site storage binders are compiled and sent to GRM for storage. GRM stores the binders for 25 years then they are destroyed. All study documents can be recalled from GRM within 24 to 48 hours of an investigator s request.

Is IRB Approval Sufficient to Activate Dispensing of Investigational Drugs? No. The study must be reviewed by pharmacy to ensure we have the capabilities to store and manipulate the investigational product This is especially relevant as we are seeing more and more biologics, stem cells, and human tissue There are complex storage & compounding capabilities not yet available: -70 freezer & Liquid Nitrogen both being installed tentatively in summer 2014 Viruses can not be manipulated in any pharmacy hoods Studies related to human tissue must be manipulated in the Cytology lab in a purified biological safety cabinet

Where Can I Find an IDDS Template to Fill Out? A blank copy of the IDDS template is on file with the research pharmacist. This can be provided to you via email upon request. Completed copies are stored electronically and in each pharmacy binder to be placed into the patient s chart prior to the first dose of study drug being administered.

What are Common Errors Seen on the IDDS? Members of the study team and primary contact information incorrect or out of date. IRB number missing from the form Information regarding the excipient in placebo excluded (important if patient has a lactose allergy) Drug-drug & drug-food interactions incomplete The research pharmacist can assist you in completing this form and performs the final review

Things to Remember. Contact the IDS pharmacist as early as possible when anticipating a new protocol Remember to budget for IDS services Notify the IDS pharmacist about the status of each study (termination, extension, changes in protocol, etc.) Provide plenty of notice for upcoming monitor visits Provide notice regarding patient schedules and visits

Things to Remember Provide accurate and up to date grant/foapal numbers and IRB number Inpatient-physician on the study team must enter complete electronic orders in a timely manner Outpatient-Provide complete and signed orders in a timely manner Outsourcing of pharmacy services must be done with the knowledge and approval of the IDS

Future IDS Support Digital temperature monitoring devices -70 freezer being installed summer 2014 Liquid nitrogen storage being installed Summer 2014 EPIC inpatient installation Looking into Vestigo electronic IDS management (McCreadie Group) Separate research pharmacy

Additional Questions?

Contact Information Jennifer Colon, PharmD, MS, MBA Office (215) 707-9346 Cell (267) 639-0014 Pharmacy Administration-Rock Pavilion, Zone B, Basement (across from the cafeteria entrance) Jennifer.Colon@tuhs.temple.edu