Drug Accountability. Kevin E. Anger PharmD, BCPS Manager Investigational Drug Services Brigham and Women s Hospital

Transcription

1 Drug Accountability Kevin E. Anger PharmD, BCPS Manager Investigational Drug Services Brigham and Women s Hospital

2 Session Objectives Define drug accountability and drugs in need of these accountability processes Discuss best practices, regulatory requirements surrounding drug accountability Describe key drug accountability processes

3 Disclosures The author of this presentation has no disclosures concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation

4 Session Outline Define investigational drugs and drugs in need of drug accountability records Best practice and regulatory requirements International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice CMS/ The Joint Commission AAHRPP FDA requirements/expectations Investigator, sponsors FDA approach Drug accountability processes Investigational Drug Service or Research Pharmacy Logs and Records

5 Drug Accountability Defined Drug accountability is the process of documenting all aspects of drug receipt, storage, use, and disposition so that a full accounting of each unit can be made.

6 Poll the Audience: Which of the following types of drugs is subject to research drug accountability? Investigational drugs Investigational new drugs Investigational Products Commercially available drugs

7 Investigational Drug Nomenclature Study Drug: Any drug used in a research study Trade or commercial drug: is FDA approved for use in the United States Investigational New Drug: A drug or biological product that is used in a clinical trial but has not been approved by the Food and Drug Administration (FDA) (the drug is either not available for a doctor to prescribe or is available but has not been approved by FDA for the use being studied). Investigational drug: a trade and/or investigational new drug being used in a research protocol. Investigational Product: A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use. ICH E6 GCP; 1.33

8 Poll the Audience: Which group drives the regulations of drug research and accountability? FDA Partners IRB Massachusetts DPH Research sponsors

9 What rules do I have to play by Federal with Investigational Drugs? FDA DEA State DPH/board of pharmacy Heath System/Hospital IRB Institutional Policies and Procedures CMS/Joint Commission Sponsor Drug accountability = Rules/regs + resources = Call IDS pharmacy

10 Key AAHRPP Accreditation Organization (Standard I-7): Standards The Organization has and follows written policies and procedures to ensure that the use of any investigational or unlicensed test article complies with all applicable legal and regulatory requirements. IRB (Standard II-3): The IRB or EC approves each research protocol or plan according to criteria based on applicable laws, regulations, codes, and guidance. Researcher Standard III-2: Researchers and Research Staff meet requirements for conducting research with participants and comply with all applicable laws, regulations, codes, and guidance; the Organization s policies and procedures for protecting research participants; and the IRB s or EC s determinations. AAHRPP = Association for the Accreditation of Human Research Protection Programs

11 Investigational Drugs in the eyes of The Joint Commission The JC considers all investigational drugs to be high risk medications = pharmacy controls MM The hospital safely manages investigational medications Hospital s written process specifies that the pharmacy controls the storage, dispensing, labeling, and distribution of investigational medications.

12 Best Practice on human research trials International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good clinical practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. ICH E6 GCP;

13 ICH/FDA GCP: Investigator Responsibilities Responsibility for investigational product(s) accountability at the trial site(s) rests with the investigator/institution Where allowed/required, the investigator/institution may/should assign some or all of the investigator's/institution s duties for investigational product(s) accountability at the trial site(s) to an appropriate pharmacist or another appropriate individual who is under the supervision of the investigator/institution. ICH E6 GCP; 4.6

14 ICH/FDA GCP: Investigator Responsibilities The investigator/institution and/or a pharmacist who is designated by the investigator/institution, should maintain records of product delivery, inventory onsite, use by subject and return or disposition of unused products. Records should include dates, quantities, batch/serial numbers, expiration dates, and the unique code numbers assigned to the investigational product(s) and trial subjects. Investigators should maintain records reconcile all investigational product(s) received from the sponsor. ICH E6 GCP; 4.6

15 ICH/FDA GCP: Investigator Responsibilities Instructions for drug accountability Shipping records for at least an initial receipt of IP(s) and subsequent shipments. Ongoing accountability records and final records after study closure ICH E6 GCP; 8

16 FDA inspector expectations/targets Physical drug storage and labeling Documentation Accountability logs Patient cards or dispensing records Drug integrity testing (COA, temperature) Disposition records (destruction, transfer) Conduct a reconciliation process based upon available records

17 What we never want to see Dear Dr : During the period to, Investigators from the Food and Drug Adminstration (FDA), inspected your conduct of clinical studies under IND At the end of the inspection, a Form FDA 483 was issued to you. We determined that you violated regulations governing the proper conduct of clinical studies involving investigational new drugs; as published in Title 21; Code of Federal Regulations (CFR). The applicable provisions of the CFR are cited for each violation.

18 You failed to. Form 483 Provide adequeate source documents Maintain product accountability records for the quantity of the test article and the date of receipt. Provide or maintain complete/accurate accountability records on dispensing or distribution Account for missing study drug Document the destruction of the contaminated vials

19 IDS Pharmacy and Drug Accountability The PI delegates the entirely or components of drug accountability to the IDS Pharmacist IDS Pharmacy is involved in: Inventory management and security Dispensing (labeling) Temperature monitoring Chain of custody Disposition or destruction

20 What is the pharmacist doing to maintain drug accountability Record availability (Paper and electronic) Investigational Brochure Most recent approved protocol Policies and Procedures Drug Package Slip (record of receipt: date received, who received drug, amount) Pharmacy inventory tracking system (database, log) Copy of Investigational Drug Label Patient card/subject card or dispense reports Electronic documentation: EPIC and IDS-IS (BWH)

21 Inventory Management: Drug Receipt Documentation Documentation by the authorized IDS pharamcist: Quantity of study product received Reference numbers Acceptability of condition of shipment Date IP received Signature of IDS staff member Combination of paper based and electronic methods

22 Drug Dispensation Documentation by the authorized IDS pharamcist using paper and electronic resources Authorized prescriber Patient information Dose, dilution Lot/batch/kit# Expiration dates Preparation documentation Ex. Thaw times for frozen products 21 CFR (a) and (a)].

23 Chain of Custody Documentation Drug administation documentation (when applicable) Physcian, Nurse, PA, pharmacist Administration route, time Drug Dispostion Pharmacist returns product to the IND holder/ sponsor Destroys if instructed by the IND holder/sponsor

24 What Resources are used for Drug Accountability? Internal and external drug accountability logs Types of log used Electronic logs and reports (internal and external programs) Paper logs (PDF, excel, word) Sponsors often want their study specific form used for accountability Double documentation is common to meet sponsor and institutional accountability standards

25 Pearls of the Accountability Log Real time logging Patient or subject card may be helpful adjunct Flagging blinded studies Use of (+) or (-) for inventory changes Crossing out of unused lines depending upon paper based log structure Crossouts, adjustments, red ink, and white out of drug quantities are auditor red flags!

26 NIH toolkit example IP Accountability log Investigational Product Accountability Log: Stock Record Name of Institution: Investigator Name: Protocol No.: Protocol Title: Product Name: Manufacturer: Dose Form and Strength: Dispensing Area: Line No. 1. Date Dispensed To / Received From Dose Quantity Dispensed and/or Received Ex. 15Feb2012 Manufacturer 10 mg tabs Balance Forward / Balance Lot No. Recorder s Initials JAD

27 National Cancer Institute Drug Accountability Log

28 Example Sponsor Provided Drug Accountability Log

29 Example Electronic log Report from BWH IDS-IS

30 How can the investigator help IDS with drug accountability? Communication, communication, communication Drug shipments notifications Working with sponsors Ensuring the IDS has the resources needed to support accountability needs Reaching out to our service upstream of the grant and IRB process

31 Key Takeaways on Drug Accountability With good drug accountability, at any stage, the investigator, pharmacist, and the sponsor should know where the investigational products are located Drug accountablity is a key target of the many agencies involved in overseeing investigaitional drug research studies Working with your research pharmacist is key to ensuring drug accountability documentation is in audit proof

32 References and Recommended Readings Guidance for industry. E6 good clinical practice, consolidated guidance. Rockville, MD : U.S. Dept. of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Control : Center for Biologics Evaluation and Research. pdf ASHP guidelines on clinical drug research. American Society of Health-System Pharmacists. Am J Health Syst Pharm Feb 15;55(4): FDA investigations operations manual (IOM) Medication Management Overview (Hospital). Standard MM The Joint Commission E-edition. Jan 1, 2012 AAHRPP Accreditation Standards. NIH toolkit for clinical researchers