Operational Rules

Investigational drug studies conducted in CMMC must be managed by the

investigational drug service pharmacy. The principal investigators are not allowed to manage the drugs by themselves, unless it is necessary and justified by the trial protocols and approved by the hospital. When following ICH-GCP (E6) the management of the investigational drug should comply with the following requirements:

5.1 Manufacturing, handling, and storage of investigational drug is in accordance with applicable good manufacturing practice. When receiving the

investigational drug, check the valid period of its IND permit and the distributor authorization documents in order to verify the drug is manufactured, handled, and stored in accordance with good manufacturing practice.

5.2 Investigators should maintain records that document adequately that the participants are provided the doses specified by the protocol and reconcile all investigational products received from the sponsor.

6. Definitions

6.1 Investigational Drugs:

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.

6.2 Institutional Review Board (IRB):

The committees possess a breadth of knowledge include in scientific and nonscientific allowing them to review a large range of research projects. This group review serves an important role in the protection of the rights and welfare of human research subjects.

6.3 Blinding:

A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single blinding usually refers to the subject(s) being unaware, and double blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s).

6.4 Investigator:

Investigator means an individual who actually conducts a clinical investigation (i.e. , under whose immediate direction the drug is administered or dispensed to a subject). In the event an investigation is conducted by a team of individuals, the investigator is the responsible leader of the team.

6.5 Sponsor:

Sponsor means a person who takes responsibility for and initiates a clinical investigation.

6.6 Contract Research Organization:

Contract research organization means a person that assumes, as an independent contractor with the sponsor, one or more of the obligations of a sponsor, e.g., design of a protocol, selection or monitoring of investigations, evaluation of reports, and preparation of materials to be submitted to the Food and Drug Administration.

7. Process

8. Content

8.1 Receipt and inventorying of study drug

8.1.1 Persons responsible: investigational drugs service pharmacist

8.1.2 Procedure: Upon receipt of the study drug, sponsor should provide intact information for investigational drugs according to 『Chi Mei Medical Center

investigational drugs application from』, inventory the shipment, ensuring that the information on the packing slips matches exactly with what has been sent to the site, including amount, Lot numbers, quantity per carrier/container.

8.1.2.1 Verifying that protocol number, protocol name, lot number, drug strength, dosage form, amount, Batch/serial numbers, validity period, appearance was intact, if there have any discrepancies, promptly bring to the attention of the sponsor.

8.1.2.2 Confirming the receipt, shipment, expiration dates, or other disposition information of the investigational drugs is correct, sign the receipt and return to the sponsor.

8. 2 Storage of study drug

8.2.1 Persons responsible: investigational drugs service pharmacist

8.2.2 Procedure:

8.2.2.1 All study drug inventory is labeled with IRB identification and stored separately from other commercial drug products under appropriate stability conditions and securely locked.

8.2.2.2 Study drug will be stored according to the storage requirements detailed in the protocol or supplied by the sponsor in a supplementary document.

8.2.2.3 Ensure that study drug is stored at the appropriate temperature/humidity, maintaining a storage area temperature/humidity log, promptly bring any discrepancies to the attention of the research nurse and Sponsor/supplier of the drug.

8.3 Registration of drug’s use in hospital for electronic prescribing systems 8.3.1 Persons responsible: investigational drugs service pharmacist

8.3.2 Procedure:

8.3.2.1 Set up the investigation drug code in the hospital according to the pharmacological classification.

8.3.2.2 Completing the Investigational Drugs Data Sheet with information on the dispensing procedure on computer setting system.

8.3.2.3 Set up the investigational drugs package information

8.3.2.4 Set up the principle investigator and co-investigator as the authorized prescribers.

8.3.2.5 Deliver the copy of Investigational Drugs Data Sheet on computer setting system to the principle investigator for prescribing the study drug.

8.4 Dispensing and returning of investigational drugs

8.4.1 Persons responsible: principal investigator, investigational drugs service pharmacist, study coordinators (research nurse)

8.4.2 Procedure:

8.4.2.1 Investigational drugs should be dispensed to subjects only by Interactive Voice Response System ( IVRS)/Interactive Web Response System (IWRS), utilizing the telephone or tone dialers or internet. Research nurse login to the system to get the drug encoding order and printed.

8.4.2.2 Research nurse take IVRS/IWRS drug encoding order and special

prescription for clinical trial prescribe by principle investigator to obtain the same encoding investigational drug from investigational drug service pharmacist.

8.4.2.3 Order verification by a pharmacist before dispensing: protocol number, patient initials/Identifier, drug code, drug name, drug strength, dosage from, Batch/serial numbers, Lot number, expiration dates.

8.4.2.4 Filling the drug accountability records, when an inventory count is done, the current balance in stock equals the balance recorded in the drug

accountability records.

8. 4.2.5If there any unused investigational drugs that because the participant withdraw from the study or miss the dose, study site should return any unused drugs to the investigational drug service pharmacy. Used product(s) will be stored in a location separate from unused supplies, inventory count and record amount of unused, Lot number, expiration date.

8.4.2.6 Any return of unused investigational drugs cannot be dispensed again.

8.5 Return of study drugs

8.5.1 Persons responsible: investigational drugs service pharmacist, coordinators (research nurse)

8.5.2 Procedure:

8.5.2.1 At the conclusion of the study, ensure that all documentation regarding receipt, storage, dispensing, and return of used containers is complete, accurate, and ready for review at the monitor’s termination visit. Ensure that the study drug is available for the monitor to inventory and prepare for return shipment to the sponsor/CRO.

8.6 Maintain investigational drug documentation

8.6.1 Persons responsible: investigational drugs service pharmacist 8.6.2 Procedure:

8.6.2.1 All study drugs records shall be retained for 2 years after a marketing application is approved for the drug. However, these documents should be retained even longer if required by applicable regulatory requirements or else agreed with the sponsor.

9. ANNEX

9.1 ANNEX 1: Department of pharmacy, Chi Mei Medical Center. Investigational Drug Service application Form (F-5500-001)

9.2 ANNEX 2: Department of Pharmacy, Chi Mei Medical Center. Investigational drug room temperature/humidity-daily manual recorded temps (F-5500-002) 9.3ANNEX 3: Department of Pharmacy, Chi Mei Medical Center. Investigational drug

refrigerators -daily manual recorded temps (F-5500-003)

9.4 ANNEX 4: Department of Pharmacy, Chi Mei Medical Center. Investigational drug Accountability Record (F-5500-004)

9.5 ANNEX 5: Department of Pharmacy, Chi Mei Medical Center. Investigational Drug Dispensing Sheet(F-5500-005)

Department of Pharmacy, Chi Mei Medical Center