Presentation on theme: "Introduction to Research Pharmacy Investigational Drug Control and Patient Safety CUMC RP Robert B. MacArthur, Pharm.D."— Presentation transcript:
1Introduction to Research Pharmacy Investigational Drug Control and Patient Safety CUMC RP Robert B. MacArthur, Pharm.D.
2“ Why does it take so long and cost so much for me to get my study pills ? “
3TopicsWhat, Why, and How about CUMCRP Labeling Some FDA and ISMP Standards and Requirements CPOE Revenue and Expenses
4What Do We Do ?InvestigationalDrug Management andDispensingCompoundingClinical Trial KitsPharmacokinetic Study Design and SupportInteractive Voice Response System (IVRS)Multicenter clinical trial drug distribution
5CUMC Research Pharmacy – Locations CUMC/NYPH CampusIrving Pavilion IP-749Black Building, Basement B-30,New Jersey17 Smith Street, Englewood NJWebsite:
6CUMC Research Pharmacy – Production Active Studies - ≈New projects/month ≈Dispensed products/month ≈ 300Destroyed products/month ≈ 125Kits/month ≈ 360Shipments/month ≈ 160
7Why?Adds value to the clinical research capabilities offered by the medical centerGives Investigators the ability to adhere to GCPs in a simple, cost-effective mannerAdds an additional level of quality control to drug storage and dispensing
8Research – Early Days“…I combed the Eastman Chemical Company Catalog and other price lists for suitable phenyl compounds…They wrote back to me that they had on hand 19 different compounds analogous to Phenobarbital, and that I was welcome to them…” 1937 Putnam “…142 patients received dilantin therapy for two to 11 months… was effective in controlling convulsive seizures in a great majority of a select group of patients who were not helped by other methods or therapy…without a doubt considerably more toxic than bromides and barbituric compounds…” 1938 Merritt and Putnam
10Regulatory Issues21 CFRA sponsor shall maintain adequate records showing receipt, shipment, or other disposition of investigational drug…21 CFR…sponsor shall assure the return of all unused drug supplies from each investigator… and maintain written records…21 CFRAn investigator is required to maintain adequate records of the disposition of the drug, including dates, quantity, and use by subjects…investigator shall return the unused drug supplies to the sponsor
11Routine FDA Inspection Findings 1977 - 1990, 2308 inspections Most Common Deficienciesconsent form problems 54%protocol non-adherence 26%drug accountability problems 25%J Clin Pharmacol 1990;30:
12FDA Inspection Findings Drug Accountability On-going accountability does not match CRFMedication started before IRB approvalPoorly maintained on-going drug accountabilityMaintained only in CRF, not independentlyTest drug not dispensed in sequential orderDiversion of drug to animal studies without PI or sponsor approval
13Microsoft Visual Basic for Applications (VBA) is used to create screens. Microsoft Access database management system is used to store data.Client / Server based system with database backend residing on departmental server. Application front-end installed on each PC workstation. No Web-based access to the system.Record of system logins are maintained. Record of user creating each kit is recorded.
181906 Legislation Food and Drug Act Prohibited interstate commerce of adulterated or misbranded food and drugs, unlawful to add ingredients that would represent a health hazard, Food and drug labeling cannot be misleading1937 Tragedy S.E. Massengill Company DIETHYLENE GLYCOLmarkets an oral liquid sulfanilamide preparation using diethylene glycol as a solvent. Several deaths result1938 Legislation Federal Food, Drug and Cosmetic Act includes FDA authority to inspect sponsors, CROs, Investigators, IRBs 1941 Legislation Agency batch approval of insulin and antibiotics. Brought medical devices and cosmetics under FDA perview. Prohibited false therapeutic claims on labeling, drugs had to be labeled with adequate instructions, FDA inspections of factories were authorized, drug manufacturing and controls, drugs had to be shown to be safe before they could be marketed, birth of the NDA [505(b)(1)]1955 Tragedy Cutter Laboratories polio vaccine causes 260 cases of polio, including 192 cases of paralytic polio 1965 Legislation Drug Abuse and Control Amendments1960 Tragedy Thalidomide British Medical Journal publishes about neurotoxicity Withdrawan in Germany for causing congenital abnormalities. Complete US drug recall, doses unaccounted for, 17 cases of thalidomide-induced phocomelia identified1962 Legislation Kefauver, Kelsey Amendments Signed Manufacturers had to prove that drugs were effective, as well as safe, going back to Experimental subjects to be given informed consent, FDA regulation of clinical investigations, GMP requirements, new drugs could only be marketed with FDA assent, with no limitation on approval time. FDA inspectors have access to establishment records
19FDA-IND Labeling Regulations Sec. 312 FDA-IND Labeling Regulations Sec Labeling of an investigational new drug(a) On the immediate package… "Caution: New Drug--Limited by Federal (or United States) law to investigational use.“(b) The label or labeling of an investigational new drug shall not bear any statement that is false or misleading in any particular and shall not represent that the investigational new drug is safe or effective for the purposes for which it is being investigated.(c) The appropriate FDA Center Director, according to the procedures set forth in or of this chapter, may grant an exception or alternative to the provision in paragraph…. (a) of this section, to the extent that this provision is not explicitly required by statute, for specified lots, batches, or other units of a human drug product that is or will be included in the Strategic National Stockpile.
20FDA-NDA Labeling Regulations The United States Pharmacopeial Convention has established requirements for containers which are described in many of the drug product monographs in The United States Pharmacopeia/National Formulary (USP/NF)…..These requirements are defined in the "General Noticesand Requirements" (Preservation, Packaging, Storage, and Labeling) section of the USP.
21Labeling Investigational Drugs No patient instructionsNo expiration date, retest date onlyWhat does one do with a retest date?
22Labeling Investigational Drugs Detailed instructionsabout how to pushtablets throughblister pack…in 11languagesFont too small to readNot Childproof
23Minimal product labeling Beautiful syringe labeling in French
24Storing Investigational Drugs One Study of 2 Active Drugs5 Dosage FormsDrug A, Drug A PlaceboDrug B, Drug B PlaceboDrug A or B (blinded active)4 Dosing Phases each with aSeparate Drug SupplyTitrationMaintenanceConversionAdjustment2 shelves per study
25What pharmacists need to focus on Over 30,000 Dispensing Errors Have Been Voluntarily Reported In The Last 3 Years From Outpatient Pharmacies in Hospitals To U.S. PharmacopeiaWhat pharmacists need to focus onSenator J D. Klein
26About 1 in 184 Dispensing Errors Reported by Outpatient Pharmacies in Hospitals Caused Harm to Patients1 in 184 errors are harmfulE= temporary harm to the patient and required interventionF= temporary harm to the patient and required prolonged hospitalizationG= permanent patient harmH= required intervention necessary to sustain lifeI= contributed to or resulted in a patient's death
27ISMP errors with investigational drugs “…syringes are labeled with an identification number [only].“Once the syringes are removed from the box, the carton label containing important information is lost….”“…license plate-type code name changes name to generic name. The code name remains on the product label, but the research team refers to and orders the drug by its new generic name. ..”
28Pharmaceutical Industry estimates of in hospital investigational drug dispensing error rates are typically 4 – 6 % Pharmacist training programs are improving, via pharmacy manuals, on-line training, pictogram drug preparation instructions
29ISMP error potential investigational drugs “…Many investigational drugs are labeled using a very small font size;… drug packages for active and placebo look remarkably similar…”“…drugs are not supplied inunit-dose packages. Additionally,vial sizes of parenteral drugsare sometimes inappropriate…”5 ml dose, 50 ml vial
30Standard LabelingAgent dispensed to study subjects should be clearly labeled as an investigation drug.Caution: Drug Limited by Federal Law to Investigational Use OnlyWarning LabelsSubject Name / Hospital MRNSubject Study NumberHospital or Clinic NameAdministration instructionsAccepted name of drug and doseNumber of units or total volumeDate agent prepared and expiration dateIRB numberOrdering physician name and pharmacist nameName, address and phone number of dispensing pharmacy
32CPOE and EPRESCRIBINGThe first national e-prescribing conference followingthe release of new rules and regulations borne from theMedicare Improvements for Patients andProviders Act of 2008 (MIPPA)The World Health Care Congress Leadership Summit on – ePrescribing & Medication Management Nov. 17, 2008 Westin Tyson's Corner – Falls Church, VA
33Computerized Physician Order Entry RPH Assigned, 1st DraftDraft completedRPh, ReviewedSent to nursing for reviewReturned to RPh for editsSent to Eclypsis ITReceived back from Eclypsis ITScreen Shot in Review by RPhScreen Shot sent to nursingScreen Shot sent to Eclypsis ITOrder set not finalized by PIOrder set approved by PIAll signatures
39NYPH Policy CUMC Policy CUMC and NYPH Investigational Drug Policies JCAHO Requirement Distribution of investigational drugs administered to patients cared for within a health care organization be under the central control of the hospital pharmacy departmentNYPH PolicyCUMC PolicyAny use of an investigational drug must be approved by the Columbia University Institutional Review BoardAll research protocols using investigational drugs must contain the investigational drug information required to be provided in a Columbia University IRB submission.Any use of an investigational drug must be approved by the Columbia University Institutional Review BoardAll research protocols using investigational drugs must contain the investigational drug information required to be provided in a Columbia University IRB submission.
40Orders in Hospital medication profiling system CUMC and NYPH Investigational Drug Policies JCAHO Requirement Distribution of investigational drugs administered to patients cared for within a health care organization be under the central control of the hospital pharmacy department.NYPH PolicyCUMC PolicyOrders in Hospital medication profiling systemOrders must be written and made available in the patient’s medical record and pharmacy medication profiling system.
41CUMC and NYPH Investigational Drug Policies JCAHO Requirement Distribution of investigational drugs administered to patients cared for within a health care organization be under the central control of the hospital pharmacy department.NYPH PolicyCUMC PolicyPharmacy Dept will order, store, inventory, dispense, destroy/return all investigational drug.The RP will order, store, inventory, dispense and destroy/ return all investigational drug.
42Pharmacy Department will only dispense with a valid order. CUMC and NYPH Investigational Drug Policies JCAHO Requirement Distribution of investigational drugs administered to patients cared for within a health care organization be under the central control of the hospital pharmacy department.NYPH PolicyCUMC PolicyPharmacy Department will only dispense with a valid order.The RP will only dispense an investigational drug subsequent to a valid order by an authorized investigator.
43Net Revenue per Project over 9 Years Per project revenue by research groupOnly group 1 has all values above $0.00Groups 3 and 4 are all served without revenueGroup 0 and 1 are used to supplement losses in all other groups
44Revenue:Expense Ratios over 9 years Close to 1.0
45“That Research Pharmacy sure does a great job ! “
46Thanks for listening, and for supporting safe dispensing practices!