investigational product accountability - UKM Medical Centre

Definition of InvestigationalProduct (IP)3 A pharmaceutical form of an active ingredient[including plant/animal-derived medicinal products]or placebo being tested or used as a reference ina clinical trial, including a product with amarketing authorization when used or assembled(formulated or packaged) in a way different fromthe approved form, or when used for anunapproved indication [(off-label use)], or whenused to gain further information about anapproved use.(ICH-GCP 1.33); [Malaysian GCP 1.38]GCP, UKMMC, 11-Jun-2012

Sponsor’s Responsibility6 5.13 Manufacturing, Packaging, Labelling and CodingIP(s) Ensure IP (including active comparators and placebo) ischaracterised as appropriate to the stage ofdevelopment of the products Ensure IP is manufactured in accordance with anyapplicable GMP Ensure IP is coded and labeled in a manner that protectsthe blinding (labeling should comply to regulatoryrequirements)GCP, UKMMC, 11-Jun-2012

Sponsor’s Responsibility7 5.13 Manufacturing, Packaging, Labelling and CodingIP(s) (continued) Determine acceptable storage temperatures, conditionsand times Determine reconstitution fluids and procedures Determine devices for product infusion Inform all parties of these determinantsGCP, UKMMC, 11-Jun-2012

Sponsor’s Responsibility8 5.13 Manufacturing, Packaging, Labelling and CodingIP(s) (continued) Ensure IP is packaged to prevent contamination andunacceptable deterioration during transport and storage Ensure a mechanism that permits rapid identification of theproduct(s) in case of medical emergency (“blind breaking”),but not permit undetectable breaks of the blinding For an IP with formulation changes, information on whetherformulation changes will affect the pharmacokinetic profile ofthe IP should be available prior to the IP being used.GCP, UKMMC, 11-Jun-2012

Sponsor’s Responsibility9 5.14 Supplying and Handling IP(s) Supply investigators/institution with IP after all requireddocumentation is obtained Ensure imported clinical trial drugs go through customs at alltimes Ensure written procedures include instructions that theinvestigator/institution should follow for handling andstorage of IP Ensure timely delivery of IP to the investigatorGCP, UKMMC, 11-Jun-2012

Sponsor’s Responsibility10 5.14 Supplying and Handling IP(s) (continued) Maintain records that document shipment, receipt, disposition,return and destruction of IP Maintain a system for retrieving IP and documenting thisretrieval Maintain a system for the disposition of unused IP and for thedocumentation of this disposition Ensure IP is stable over the period of use Maintain sufficient quantities of the IP used in the trials toreconfirm specifications, if necessary, and maintain records ofbatch sample analyses and characteristics.GCP, UKMMC, 11-Jun-2012

IP/Drug Accountability – Responsibility11 Who is responsible for IP accountability at the trialsite? Investigator? Institution? Monitor? Sponsor?GCP, UKMMC, 11-Jun-2012

IP/Drug Accountability – Responsibility12 Must the investigator personally perform IPaccountability? Yes? No?GCP, UKMMC, 11-Jun-2012

IP/Drug Accountability – Responsibility13 Who can perform IP accountability at the trial site? Study co-ordinator? Pharmacist? Ward nurse?Note: Under the supervision of the investigator orinstitutionGCP, UKMMC, 11-Jun-2012

IP Accountability Records14 What IP accountability records need to bemaintained at the trial site? Delivery/receipt of IP from the sponsor Use of IP by each study subject Return of unused IP to the sponsor Disposition/destruction of unused IPGCP, UKMMC, 11-Jun-2012

IP Accountability Records15 How do we calculate the use of IP by each studysubject?# Dispensed - # Returned/Unused = # Used What if the subject loses some of the IP?# Dispensed - # Returned/Unused - # Lost= # UsedGCP, UKMMC, 11-Jun-2012

IP Accountability Records16 How do we calculate dosing compliancepercentage?Actual # Used------------------------------ x 100%Daily # x No. of Days What is the acceptable dosing compliance rate? Refer to the study protocolGCP, UKMMC, 11-Jun-2012

IP Accountability Records17 What other details do we record for goodaccountability? Dates (e.g. receipt, reconstitution, dispensing, returnby subject, destruction and return to sponsor) Batch/serial numbers Expiry dates Unique numbers assigned to the IP Subject numbers whom the IP is assigned toGCP, UKMMC, 11-Jun-2012

IP Accountability Records18 Investigators should maintain records that documentadequately: That the subjects were provided the doses specifiedby the protocol, and That all IP(s) received from the sponsor arereconciled. Generally: Subject-level accountability log Site-level inventory log See exampleGCP, UKMMC, 11-Jun-2012

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Question 120 In a blinded placebo-controlled study, all IP must beaccounted for separately. True FalseGCP, UKMMC, 11-Jun-2012

Question 221 In an open-label study, all IP must be accounted forseparately. True FalseGCP, UKMMC, 11-Jun-2012

Question 322 The recording of IP is done when the subject completesthe study or discontinues from the study before themonitor reviews it. True FalseGCP, UKMMC, 11-Jun-2012

Question 423 For outpatient studies, the study subjects takes home theIPs. The subject must return unused IPs to theinvestigator/study co-ordinator/pharmacist. True FalseGCP, UKMMC, 11-Jun-2012

Question 524 If a subject has lost a bottle of IP, another bottle cannotbe dispensed unless allowed by the protocol. True FalseGCP, UKMMC, 11-Jun-2012

Question 625 Unused IP returned by the study subject can bedestroyed locally after recording at the IPaccountability log. True FalseGCP, UKMMC, 11-Jun-2012

Question 726 Expired IP must not be used and must be discardedimmediately to prevent accidental use. True FalseGCP, UKMMC, 11-Jun-2012

Question 827 Consult with the monitor/sponsor if there are anyissues/errors noted regarding IPs (e.g. situations notstated in the protocol). True FalseGCP, UKMMC, 11-Jun-2012

IP Storage28 Temperature control Temperature recording – every working day? Accepted temperature range noted? Temperature excursion – contact monitor/sponsor Thermometer – calibrated? Responsible person Access control Secure location Responsible personGCP, UKMMC, 11-Jun-2012

IP Use29 According to the protocol Reconstitution for IV or oral use? Storage condition and shelf life after reconstitution? Dispensing instructions to the subject• Correct use• Check, at appropriate intervals, that each subject follows theinstructions properly Administration instructions to study/support staff Disposal/retention of used bottles, vials, bags, blistercards, etc. Precautions (e.g. cytotoxic agents)GCP, UKMMC, 11-Jun-2012

Conclusion30 IP accountability To the sponsor• GCP• ProtocolGCP, UKMMC, 11-Jun-2012

Conclusion31 IP accountability To the Malaysian Drug Control Authority• Clinical Trial Import Licence (CTIL) Guidelineshttp://portal.bpfk.gov.my/index.cfm?menuid=71&parentid=69GCP, UKMMC, 11-Jun-2012

Questions and Discussion32GCP, UKMMC, 11-Jun-2012

GCP, UKMMC, 11-Jun-2012 33Thank you!Terima kasih…