The Right Prescription for Working with Investigational

Drug Service at BMC

Andrew SchochAndrew Schoch

Pharmacy Intern Pharmacy Intern

Northeastern University Northeastern University

Class of 2010Class of 2010

Hyeseon Hong, Pharm.D. Hyeseon Hong, Pharm.D.

IDS Pharmacy ManagerIDS Pharmacy Manager

What is Investigational Drug Services?

IDS is a division of pharmacy, with an IDS is a division of pharmacy, with an appointed investigational pharmacist, appointed investigational pharmacist, specializing in the handling, storage, specializing in the handling, storage, labeling, and distribution of investigational labeling, and distribution of investigational agents in accordance with the most current agents in accordance with the most current regulatory requirements maintained by the regulatory requirements maintained by the FDA, Joint Commission, ICH, and GCP FDA, Joint Commission, ICH, and GCP Guidelines.Guidelines.

Do ALL study drugs need to be stored and dispensed by BMC

Pharmacy?

YESYESAll medications used in Investigational Protocols at BMC must be stored, labeled, and dispensed by BMC IDS Pharmacy. (JCAHO Medication Management Standard 7.40)

Investigational drugs must be in a securely locked, substantially constructed enclosure, with limited access to prevent theft or diversion of the substance. (CFR 312.69)

What does BMC IDS need from the Research team to get started?

A current copy of the study Protocol, all A current copy of the study Protocol, all Protocol amendments, drug brochures, IRB Protocol amendments, drug brochures, IRB Approval letter, and 1572 (if an IND study)Approval letter, and 1572 (if an IND study)

Study drugsStudy drugs IDS Charge FormIDS Charge Form Protocol activation meetingProtocol activation meeting Lead time in advance of proposed study Lead time in advance of proposed study

startup to prepare for study and get startup to prepare for study and get procedures written and in placeprocedures written and in place

Does a protocol with study drug need to be reviewed by BMC

Pharmacy?

Yes. All studies involving drugs to be used as part of a research Yes. All studies involving drugs to be used as part of a research study must be reviewed for feasibility by the BMC IDS study must be reviewed for feasibility by the BMC IDS

Manager or Director of Pharmacy and signed Manager or Director of Pharmacy and signed priorprior to IRB to IRB review. review.

-IRB approval alone is not sufficient to activate dispensing of investigational medication from the IDS.

How do I obtain study drugs from BMC IDS Pharmacy?

For any For any outpatientoutpatient study medication, a study medication, a Study Drug Study Drug Request FormRequest Form must be faxed to IDS Pharmacy must be faxed to IDS Pharmacy

A A Study Drug Request FormStudy Drug Request Form must be signed by either a must be signed by either a primary investigator or a sub-investigator (CFR 312.61)primary investigator or a sub-investigator (CFR 312.61)

Last page of informed consent form if first dispensingLast page of informed consent form if first dispensing Call BMC IDS Pharmacy if a subject is waiting at clinicCall BMC IDS Pharmacy if a subject is waiting at clinic Written expiration/retest date on the study material Written expiration/retest date on the study material

(GCP 5.14.5)(GCP 5.14.5)--Written sponsor/manufacturer memo on expiration/retest dateWritten sponsor/manufacturer memo on expiration/retest date-Certificate of analysis per GMP-Certificate of analysis per GMP-Regulatory affairs agency (FDA) memo to a sponsor-Regulatory affairs agency (FDA) memo to a sponsor

How are the drugs handled for Inpatient protocols?

For For inpatient inpatient study medication, an order must be put in via study medication, an order must be put in via SCM. Once the order has been verified, study drug will be SCM. Once the order has been verified, study drug will be placed inside the placed inside the PyxisPyxis under “Investigational Study Drug” under “Investigational Study Drug”

Parenteral study medications are prepared according to the Parenteral study medications are prepared according to the specific protocol. All parenteral study drugs are given a 24 specific protocol. All parenteral study drugs are given a 24 hour expiration unless otherwise designated by the hour expiration unless otherwise designated by the manufacturer.manufacturer.

What if someone enrolled in an outpatient study is admitted to BMC?

Once admitted, IDS Pharmacy is contacted by research Once admitted, IDS Pharmacy is contacted by research team.team.

If PI wants to continue the study drug during If PI wants to continue the study drug during hospitalization, an order is placed into SCM and the drug hospitalization, an order is placed into SCM and the drug is loaded into the Pyxis machine on that floor.is loaded into the Pyxis machine on that floor.

PI’s consent of continuation must be documented in PI’s consent of continuation must be documented in ‘Additional Information’ in SCM‘Additional Information’ in SCM

Mr. Smith was admitted to BMC E6N. He is taking an experimental study drug from a BMC protocol in

a stroke prevention trial. What should the covering physician do?What should the covering physician do?

Research team should be contacted by physician to see if it is ok Research team should be contacted by physician to see if it is ok to continue study drug and to ensure safety and rule out any to continue study drug and to ensure safety and rule out any contraindications based on the patient’s current conditioncontraindications based on the patient’s current condition

Upon requestUpon request, IDS pharmacy will provide information about the , IDS pharmacy will provide information about the study medication as well as contact information of the Principal study medication as well as contact information of the Principal Investigator and research team.Investigator and research team.

The physician should see if patient can bring in their own study The physician should see if patient can bring in their own study medicationmedication

***If research team is on a pager, please respond to your pager. BMC ***If research team is on a pager, please respond to your pager. BMC IDS Pharmacy cannot verify the scm order without research team IDS Pharmacy cannot verify the scm order without research team doctor’s approval***doctor’s approval***

Who should be contacted if a patient is admitted who is currently enrolled

in a non-BMC study? Shall be handled in accordance with the “Patient’s Own Shall be handled in accordance with the “Patient’s Own

Medication” policyMedication” policy Ordering physician must consult with the outside Ordering physician must consult with the outside

investigator and get their permission to continue therapy investigator and get their permission to continue therapy while subject is inpatient at BMCwhile subject is inpatient at BMC

Order is entered into SCM as a nonformulary medicationOrder is entered into SCM as a nonformulary medication Note in the additional instructions field the primary Note in the additional instructions field the primary

investigator contact and their approvalinvestigator contact and their approval Ordering physician shall provide documentation on Ordering physician shall provide documentation on

identity of the study medication and appropriateness of identity of the study medication and appropriateness of useuse

How does a physician put an order into SCM for an investigational study drug?

Select Select “Investigational Study Drug”“Investigational Study Drug” This selection will require the physician to enter the This selection will require the physician to enter the study study

drug namedrug name, , dosage strengthdosage strength, , dosagedosage, , BMC Protocol #BMC Protocol #, , Protocol TitleProtocol Title, , name of PIname of PI, and , and note of approvalnote of approval by PI or by PI or sub-investigatorsub-investigator

Additional InstructionsAdditional Instructions Details of the study to communicate to BMC nursing Details of the study to communicate to BMC nursing

staffstaff

Investigational Drug Storage & Handling

Stored according to Controlled Substances Act (CFR Stored according to Controlled Substances Act (CFR 312.69)312.69)

Acceptable storage conditions, temperature, storage times, Acceptable storage conditions, temperature, storage times, reconstitution requirements (if applicable) should be reconstitution requirements (if applicable) should be determined by the sponsor for all investigational products determined by the sponsor for all investigational products (GCP 5.13.2)(GCP 5.13.2)

Packaging of study drugs to prevent contamination and Packaging of study drugs to prevent contamination and deterioration during transport and storage (GCP 5.13.3)deterioration during transport and storage (GCP 5.13.3)

Address adequate and safe receipt, handling, storage, Address adequate and safe receipt, handling, storage, dispensing, retrieval of unused product from subject, dispensing, retrieval of unused product from subject, return of unused drugs (GCP 5.14.3)return of unused drugs (GCP 5.14.3)

Investigational Drug Storage & Handling

Storage of study drugs under appropriate Storage of study drugs under appropriate conditions of temperature, humidity, and light so conditions of temperature, humidity, and light so that the identity, strength, quality, and purity of that the identity, strength, quality, and purity of the study drugs are not affected (FDA 211.142)the study drugs are not affected (FDA 211.142)

The study drugs should be stored according to The study drugs should be stored according to regulatory requirements (GCP 4.6.4)regulatory requirements (GCP 4.6.4)

The study drugs should be used only according to The study drugs should be used only according to the protocol (GCP 4.6.5)the protocol (GCP 4.6.5)

Drug Accountability

Records of the study drug’s delivery, inventory, Records of the study drug’s delivery, inventory, use by each subject, and return/disposition of use by each subject, and return/disposition of unused drugs must be kept (GCP 4.6.3)unused drugs must be kept (GCP 4.6.3) Drug accountability records:Drug accountability records:

Shipping/Receipt logsShipping/Receipt logsPerpetual inventoryPerpetual inventoryLot numbers/Kit numbers/Expiration datesLot numbers/Kit numbers/Expiration datesPatient-specific dispensing logsPatient-specific dispensing logsRecord of final drug disposition (e.g. Record of final drug disposition (e.g.

destruction or return to sponsor)destruction or return to sponsor)

Investigational Drug Disposal(BMC Policy #8.41)

Before returning medication to IDS Pharmacy, SC shall Before returning medication to IDS Pharmacy, SC shall count and document on the bottle and any other required count and document on the bottle and any other required documents per sponsor.documents per sponsor.

Once drugs are returned to the pharmacy by the study Once drugs are returned to the pharmacy by the study coordinator, they are double checked and logged in the coordinator, they are double checked and logged in the accountability record. If there is any discrepancy, SC will accountability record. If there is any discrepancy, SC will be contacted.be contacted.

Investigational drugs are then stored under the PI’s name Investigational drugs are then stored under the PI’s name until the study monitor visits to return them to the sponsoruntil the study monitor visits to return them to the sponsor

If determined in the protocol that the drug can be disposed If determined in the protocol that the drug can be disposed of by IDS staff, it is done so per BMC policy.of by IDS staff, it is done so per BMC policy.

-Placed in marked biohazard bins to be incinerated-Placed in marked biohazard bins to be incinerated-All patient information removed on boxes-All patient information removed on boxes

Returned Drug Process

An investigator is required to maintain adequate records of An investigator is required to maintain adequate records of the disposition of the drug, including dates, quantity, and the disposition of the drug, including dates, quantity, and use by subjects. If investigation is over, the investigator use by subjects. If investigation is over, the investigator shall return the unused supplies of drug to the sponsor or shall return the unused supplies of drug to the sponsor or otherwise provide for disposition of the unused supplies of otherwise provide for disposition of the unused supplies of the drug under CFR 312.59. (CFR 312.62a)the drug under CFR 312.59. (CFR 312.62a)

Drug study records must be kept for a duration of 2 years Drug study records must be kept for a duration of 2 years following the date a marketing application is approved for following the date a marketing application is approved for the drug for the indication being investigated or 2 years the drug for the indication being investigated or 2 years after the investigation is discontinued. (CFR 312.62c)after the investigation is discontinued. (CFR 312.62c)

Site Monitor Visit Notification

Adequate notification shall be given when Adequate notification shall be given when study monitors/auditors/inspectors visit so study monitors/auditors/inspectors visit so appointments can be scheduled and appointments can be scheduled and appropriate study documents made readyappropriate study documents made ready

Utilizing IDS Services

When using BMC IDS for an upcoming study, be When using BMC IDS for an upcoming study, be sure to contact us sure to contact us beforebefore the study budget is the study budget is approved. Failing to do this may result in approved. Failing to do this may result in unexpected study costs that could have been unexpected study costs that could have been included in the study budget if considered early in included in the study budget if considered early in the negotiations with the sponsorthe negotiations with the sponsor

As the management of some studies are more As the management of some studies are more complicated than others, contact IDS for a fee complicated than others, contact IDS for a fee scheduleschedule

What is an IND and when is it needed?

The Investigational New Drug application is a request for Food and The Investigational New Drug application is a request for Food and Drug Administration (FDA) authorization to administer an Drug Administration (FDA) authorization to administer an investigational drug to humans.investigational drug to humans. IND also referred to as Form 1571IND also referred to as Form 1571

IND is required when the investigational drug is a completely new IND is required when the investigational drug is a completely new chemical chemical oror if it is intended to support a: if it is intended to support a: New indicationNew indication Change in the approved route of administration or dosage levelChange in the approved route of administration or dosage level Change in the approved patient populationChange in the approved patient population Significant change in the promotion of an approved drugSignificant change in the promotion of an approved drug

Vitamins, herbal products, and other supplements from the health Vitamins, herbal products, and other supplements from the health store?store?

The 3 Types of IND Applications Investigator INDInvestigator IND

Submitted by a physician to propose studying an unapproved drug, or an Submitted by a physician to propose studying an unapproved drug, or an approved product for a new indication/patient populationapproved product for a new indication/patient population

Emergency Use INDEmergency Use IND Allows the FDA to authorize use of an experimental drug in an Allows the FDA to authorize use of an experimental drug in an

emergency situation that does not allow time for submission of an IND emergency situation that does not allow time for submission of an IND (in (in accordance with 21CFR, Sec.312.23 or Sec.312.34). accordance with 21CFR, Sec.312.23 or Sec.312.34). Also used for patients who Also used for patients who do not meet criteria of an existing study protocol or if an approved study do not meet criteria of an existing study protocol or if an approved study protocol does not exist.protocol does not exist.

Treatment INDTreatment IND Submitted for experimental drugs showing promise in clinical testing for Submitted for experimental drugs showing promise in clinical testing for

serious or immediately life-threatening conditions while the final clinical serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes placework is conducted and the FDA review takes place

Are not intended for single patient useAre not intended for single patient use

What are the 3 broad areas the IND application must have?

Animal Pharmacology and Toxicology StudiesAnimal Pharmacology and Toxicology Studies Preclinical data to permit an assessment as to whether Preclinical data to permit an assessment as to whether

the product is reasonably safe for initial testing in the product is reasonably safe for initial testing in humans. Also included are any previous experience humans. Also included are any previous experience with the drug in humans (often foreign use).with the drug in humans (often foreign use).

Manufacturing InformationManufacturing Information Information about the composition, manufacturer, Information about the composition, manufacturer,

stability, and controls used for manufacturing the drug stability, and controls used for manufacturing the drug substance and product to ensure the company can substance and product to ensure the company can product and supply consistent batches of the drugproduct and supply consistent batches of the drug

Clinical Protocols and Investigator InformationClinical Protocols and Investigator Information Detailed protocols for proposed clinical studies to Detailed protocols for proposed clinical studies to

assess whether trials will expose subjects to assess whether trials will expose subjects to unnecessary risks. Also included is information on the unnecessary risks. Also included is information on the qualifications of the clinical investigatorsqualifications of the clinical investigators

How soon can the trial be started after the IND is submitted?

Once the IND is submitted, the sponsor Once the IND is submitted, the sponsor must wait must wait 3030 calendar days before initiating calendar days before initiating any clinical trials. During this time, FDA any clinical trials. During this time, FDA has an opportunity to review the IND for has an opportunity to review the IND for safety to assure that research subjects will safety to assure that research subjects will not be subjected to not be subjected to unreasonable riskunreasonable risk

What are the contents of the IND application (FDA 1571)?

See handoutSee handout Items 1-20Items 1-20

FDA Form 1571 Section 12FDA Form 1571 Section 12 Form FDA 1571Form FDA 1571 Table of ContentsTable of Contents Introductory StatementIntroductory Statement General Investigational planGeneral Investigational plan Investigator’s brochureInvestigator’s brochure Protocol(s)*Protocol(s)* Chemistry, manufacturing, and control dataChemistry, manufacturing, and control data Pharmacology and toxicology dataPharmacology and toxicology data Previous human experiencePrevious human experience Any additional informationAny additional information

What is a 1572 form?

The 1572 is the statement of the investigator that The 1572 is the statement of the investigator that he/she will abide by the federal guidelines set he/she will abide by the federal guidelines set forth in the Code of Federal Regulations for the forth in the Code of Federal Regulations for the use of drugs in an investigational setting.use of drugs in an investigational setting. Any study operating under an IND requires a Any study operating under an IND requires a

15721572

All BMC IDS policies and procedures can be All BMC IDS policies and procedures can be found at found at http://www.internal.bmc.orghttp://www.internal.bmc.org under the under the Pharmacy department.Pharmacy department. Policy 8.40 – Investigational Drug ServicePolicy 8.40 – Investigational Drug Service Policy 8.41 – Investigational Drug DisposalPolicy 8.41 – Investigational Drug Disposal Policy 3.31 - Investigational Drug StoragePolicy 3.31 - Investigational Drug Storage

IDS Charge Sheet Information

See handoutSee handout The following fields shall be filled out:The following fields shall be filled out:

Financial Manager Name and Phone NumberFinancial Manager Name and Phone Number Name of funding agencyName of funding agency BUMC or BMC Account NumberBUMC or BMC Account Number Signature of PISignature of PI

Contact Information

Investigational Drug Services Dept.Investigational Drug Services Dept. Hyeseon Hong, Pharm.D Hyeseon Hong, Pharm.D

• Investigational Drug Services ManagerInvestigational Drug Services Manager88 East Newton Street88 East Newton StreetBoston, MA 02118Boston, MA 02118Tel: (617) 638 – 6779Tel: (617) 638 – 6779Fax: (617) 414 – 4220Fax: (617) 414 – 4220E-mail: E-mail: hyeseon.hong@bmc.orghyeseon.hong@bmc.org

Nikolina Cingel, Pharm.DNikolina Cingel, Pharm.D Rebecca Lee, Pharm.DRebecca Lee, Pharm.D Andrew Schoch, Pharmacy InternAndrew Schoch, Pharmacy Intern