Sandra Maddock & Brandy Smith BioEnterprise Presentation 9.6.12

transcript

We have studied clinical research and

regulatory compliance issues since 1999.

The Difference is in the Details

Drugs vs. DevicesPresented by:

Brandy SmithSandra Maddock

AgendaAn Overview of Drugs and Devices

Determining the Need for a Clinical Trial

Regulatory Overview

Clinical Trial Similarities

Clinical Trial Differences

FAIR Shake™- The Regulations

Regulatory Overview

Articles recognized in the official US Pharmacopoeia, official Homoeopathic Pharmacopoeia of the US, or official National Formulary

• intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease

• intended to affect the structure of any function of the body

(FDC Act, Section 201)

Overview of Drugs and DevicesDrugs

An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article… which is –

• intended for use in the diagnosis of disease… in cure, mitigation, treatment, or prevention of disease

• intended to affect the structure of any function of the body… not achieved through chemical action… or being metabolized

(FDC Act, Section 201)

Overview of Drugs and DevicesDevices

Class Description

Class I Least risky, general controls adequate; no clinical trial needed

Class II Intermediate risk, special controls needed (510k)

Class III Substantial risk devices, pre-market approval needed (IDE)

Overview of Drugs and DevicesDevice classifications

Chemical/ metabolic action

Distributed systemically

May impact metabolism of other drugs

Larger number of study subjects needed to identify side effects

Clinical Trial Always Required

Devices

Not metabolized

Acts locally

Effects structure

Smaller number of study subjects needed

Clinical trial needs are based on risk classification of device

Regulatory Overview

• In situations of a drug, a clinical trial will always be required

• However, not all devices will need to undergo a clinical trial

• The determination of whether or not a device clinical trial is required is based on a risk stratification

21 CFR 312“IND”

All Drugs require Clinical Trials

Devices

Intermediate Risk

Clinical trial MAY be required

Substantial Risk

Clinical Trial Required

Assess Risk Classification

Devices

Intermediate Risk

Substantial Risk

Class Description

}Minima

l RiskIntermediat

e RiskSubstantial

No Clinical

Trial Required

MAY Require Clinical

REQUIRES Clinical

Risk Classification

Determining the Need for a Clinical TrialRisk Stratification

Class Description

}Minima

l RiskIntermediat

e RiskSubstantial

No Clinical

Trial Required

MAY Require Clinical

REQUIRES Clinical

Risk Classification

21 CFR 312“IND”

Devices

Intermediate Risk

Substantial Risk

21 CFR 312“IND”

*Clinical Trials Always Required for New Drugs*

Clinical TrialsDrugs

Phase PurposePhase I Normal healthy volunteers

Determine metabolism and pharmacologic actionsAim= safety and tolerance

Phase II Patients with the disease or conditionSmall SampleAim= safety and effectiveness

Phase III Patients with the disease or conditionLARGER populationAim= safety and effectiveness

Phase IV Post approval studiesObtain additional information regarding risks, benefits, and optimal use

Clinical TrialsDevices

Study PurposeAlthough there are “phases” in device research, they are not as delineated as drugsPilot May conduct pilot study (strategic decision or FDA request)

Single-center or small number of multi-center sitesSmall number of subjectsSafety and tolerance

Pivotal Larger number of subjectsLarger number of sitesSafety and effectiveness

Continued Access

During PMA review of pivotal data, the FDA may grant continued use of the device and allow more subjects to be enrolled

Post Market Strategic decision or FDA’s requestMethod to collect long-term data

Feature Drug DeviceRate of technology change Low HighInfluence of physician technique Low HighPopulation size Large SmallAble to visualize performance Low HighAbility to blind treatments Easy DifficultUse of randomization High LowPhases Clear Less Clear

(pilot/pivotal)

Clinical TrialsDrugs and Devices

Regulatory Overview

21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 21CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; SPONSOR AND SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11;IRB SOPs; It’s Complicated!

Sponsor

Sponsor Requirements

Good Clinical Practice

FDA Regulations

ICH Guidelines

Protocol RequirementsInvestigator

Agreements

ISO14155

NIH Guidelines

IRB Requirements

Internal Policies

CRO/Monitor

Research Site

Regulatory OverviewWhat you need to know

Sponsor

FDA Regulations

Research Site

• Investigator(s)• Research Coordinator(s)• Other Research Administration• Institutional Review Board (IRBs)

CRO/Monitor

Regulatory OverviewOur Focus

• Requirements for conducting clinical studies

• Outlines responsibilities of the sponsors, investigators, and IRBs for conducting trials involving human subjects

Regulatory OverviewCode of Federal Regulations

Titles

Chapters

Subparts

Paragraphs

Sections

Title: CRF Title 21

Chapter: Food and Drugs

Part: 50 Protection of Human Subjects

Subpart: B Informed Consent of Human Subjects

Section: (a) – Basic Elements of Informed Consent

Section Paragraph: (1) Statement that the study involves research…

Title: CRF Title 21

Part: 312 Drugs

Part: 812 Devices

Part: 56 Institutional Review Boards (IRBs)

Part: 54 Financial DisclosuresPart: 11 Electronic Records/Electronic Signatures

Minute to Win It!

Fill in the blanks….Regarding record maintenance, an investigator must maintain accurate, complete and current records, including:

21 CFR 812.140 (1)All _____________ with another ____________, an _______, the sponsor, a monitor, or ______, including required ________________.

Title: CRF Title 21

Part: 312 Drugs

Part: 812 Devices

Title: CRF Title 21

Part: 312 Drugs

Part: 812 Devices

• ISO 14155 has been designed for medical devices

• ICH GCP has origins in the pharmaceutical industry

• ISO 14115 and ICH GCP complement one another as they are based on the same principles:– Patient protection– Documentations– Risk-benefit assessments– Ensuring data validity

Regulatory OverviewGlobal Perspective

Regulatory Overview

• Regulations that drugs and devices have in common:– 21 CFR 11 (electronic records)– 21 CFR 50 (protection of human subjects)– 21 CFR 54 (financial disclosure)– 21 CFR 56 (institutional review board)

Clinical Trial SimilaritiesRegulations

• Within 21 CFR 312 and 21 CFR 812 are many similarities:– Submit to FDA before beginning an investigation– Update annually– Amendments required when changes are made– Promotion and charging for the product– Labeling– Waivers– Product accountability

Clinical Trial SimilaritiesRegulations

Clinical Trial SimilaritiesSponsor Responsibilities

DRUGS DEVICES

•Select qualified investigators•Provide info to investigators•Ensure proper monitoring•Ensure trial is conducted in accordance with the general investigational plan and protocols

•Maintain an effective IND with respect to the investigations

•Ensure the FDA and investigators are promptly informed of significant new adverse effects or risks with respect to the drug

•Selecting qualified investigators•Provide info to investigators•Ensure proper monitoring •Ensure trial is conducted in accordance with the general investigational plan, protocol, agreement, IRB

•Ensure IRB review and approval•Ensure IRB and FDA are promptly informed of significant new information

DRUGS DEVICES

312.56: ….(paraphrased) Ensuring that the investigation(s) is conducted in compliance with the investigational plan, the signed agreement, and the applicable regulations….

812.46: (paraphrased) Ensuring compliance with signed agreement, investigational plan, applicable FDA regulations, and IRB requirements....

Clinical Trial SimilaritiesSponsor Responsibilities

DRUGS DEVICES

312.60: ….Ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations....

812.110: An investigator shall conduct an investigation in accordance with the signed agreement with the sponsor, the investigational plan, this part and other applicable FDA regulations, and any conditions of approval imposed by an IRB or FDA.

Clinical Trial SimilaritiesInvestigator Responsibilities

Lots of Similarities!

Investigator responsibilitie

s similar

Sponsor responsibiliti

es similar

Trials organized differently

(defined phases v. pilot/pivotal), but many of the

same requirements

Regulatory Overview

Agreements

Training

Payments

Adverse Events

Clinical Trial DifferencesDifferences are in the Details

In both drug studies and device studies, the FDA requires that the investigator comply with the agreements (21 CFR 312.56 and 21 CFR 812.46), however the agreements are not identical.

Clinical Trial DifferencesAgreements

• The FDA Form 1572 is the agreement mandated by the FDA to be completed by all investigators involved in a drug trial.

• The agreement describes an investigator’s qualifications and specifies his or her commitment to adhering to applicable FDA regulations.

Clinical Trial DifferencesAgreements - Drugs

Read the SMALL PRINT of the 1572, The Essential GCP Document; http://www.wlap.org/filearchive/cacr/CACR_CRE_ 2.ppt#256,1,Read the SMALL PRINT of the 1572

Read the SMALL PRINT of the 1572

SuperviseMaintain RecordsAdhere to protocolLearn investigator

brochureLet FDA inspect

rePort adverse eventsRetain recordsInform subjectsNotify IRBTrain staff

Read the SMALL PRINT of the 1572, The Essential GCP Document; http://www.wlap.org/filearchive/cacr/CACR_CRE_ 2.ppt#256,1,Read the SMALL PRINT of the 1572

Read the SMALL PRINT of the 1572

SuperviseMaintain RecordsAdhere to protocolLearn investigator

brochureLet FDA inspect

rePort adverse eventsRetain recordsInform subjectsNotify IRBTrain staff

• No standard format or specific form required• Direction provided as to what should be included in

the agreements (21 CFR 812.43)– Investigator qualifications– Commitment to conduct the study in accordance with

regulations– Commitment to supervise device use– Statement regarding involvement in research that was

terminated (if applicable)

Clinical Trial DifferencesAgreements - Devices

Training should be approached differently when beginning a drug study versus beginning a device study.

Clinical Trial DifferencesTraining

Drugs• Training on dispensing of product not likely to be needed• Burden of responsibility to comply with drug regimen lies with

patient/patient’s caregiver • A sponsor shall select only investigators qualified by training and

experience as appropriate experts to investigate the drug. 21 CFR 312.53

Devices• Training could be significant and might require the assistance of

engineers, product development, nurses, other physicians, etc.• Influence of physician technique can be very high depending on

the complexity of device study• A sponsor shall select investigators qualified by training and

experience to investigate the device. 21 CFR 812.43

Clinical Trial DifferencesTraining

Product reimbursement varies quite a bit from drugs to devices.

Clinical Trial DifferencesPayments

• Drugs are often provided free of charge to clinical sites and patients in clinical trials

• Devices expensive to produce

• Having to provide it free could cause a significant barrier to development

• For some studies, investigator could be charged for the device (then reimbursed by Medicare or private insurance) – “Category B Investigational Devices”

Clinical Trial DifferencesPayments

Due to the systemic nature of drugs, all adverse events will need to be captured and analyzed as potentially related to the drug. Devices have a local affect, and the likelihood of an adverse event being related to the device is easier to determine. For this reason, not all negative occurrences in a device study are reportable.

Clinical Trial DifferencesAdverse Events

ADEsUADEs

FDA UADEs

Source: Michaels, MB, Applied Clinical Trials, August 2011, pages 36.

• AE: Adverse Effect

• SAE: Serious Adverse Effect

• ADE: Adverse Device Effect

• SADE: Serious Adverse Device Effect

• UADE: Unanticipated Adverse Device Effect

• FDA UADE: Unanticipated Adverse Device Effect that is also SERIOUS

Clinical Trial DifferencesAdverse events

• UADEs- report to Sponsor and IRB no later than 10 days after learning of the event

• Immediately conduct investigation• If UADE presents unreasonable risks to

subjects, sponsor shall terminate all investigations within 5 working days of making that decision

Key Points

• Devices have local affect, drugs systemic

• Follow different regulatory pathways• Clinical trials very similar in

requirements• Differences lie in the details:

Agreements

Training

Payments

Adverse Events

Regulatory Overview

Let’s Shake Things Up

“You can fool all of the people some of the time, and some of the people all of the time, but you cannot fool all of the people all of the time.”

- Abraham Lincoln

You Need To Bring It!

21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; 21 CFR 50; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 21CFR 56; ICH; IRB SOPs; SPONSOR SOPs; SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11; SPONSOR AND SITE SOPs; AGREEMENTS; PROTOCOL; 21 CFR 812; 21 CFR 11;IRB SOPs; It’s Complicated!

Sponsor

Sponsor Requirement

Clinical Practice

FDA Regulations

ICH Guidelines

Protocol RequirementsInvestigator

Agreements

ISO14155

NIH Guidelines

IRB Requirements

Internal Policies

What You Need to Know

CRO/Monitor

Research Site

Adding To The Mix…

A decision about regulatory compliance made at one site for one study may not be the right decision at another site for the

same study or at the same site for another study….

Variable

Fixedversus

21 CFR 812 - IDEs

• 812.110: An investigator shall conduct an investigation in accordance with the signed agreement with the sponsor, the investigational plan, this part and other applicable FDA regulations, and any conditions of approval imposed by an IRB or FDA.

Investigator

• 812.46: (paraphrased) Ensuring compliance with signed agreement, investigational plan, applicable FDA regulations, and IRB requirements....

Sponsor

Working through the chaos

Federal RegulationsAgreementsInvestigational PlanRequirements of IRB

• Requirements for conducting clinical studies

• Outlines responsibilities of the sponsors, investigators, and IRBs for conducting trials involving human subjects

Federal Regulations

IDEs (Investigational Device Exemptions)

Protection of Human Subjects

IRBs (Institutional Review Boards)

Financial Disclosures

Electronic Records/Signatures11

FDA Regulations to Know

Federal Regulations

• Describes the procedures for the conduct of clinical investigations of devices

• Sponsor responsibilities

• Investigator responsibilities

Federal Regulations21 CFR 812 - IDEs

• 812.110: An investigator shall conduct an investigation in accordance with the signed agreement with the sponsor, the investigational plan, this part and other applicable FDA regulations, and any conditions of approval imposed by an IRB or FDA.

Investigator

• 812.46: (paraphrased) Ensuring compliance with signed agreement, investigational plan, applicable FDA regulations, and IRB requirements....

Sponsor

Federal Regulations21 CFR 812 - IDEs

• Overall conduct of a study:– Labeling – Promotion– Selection of Investigators– Monitoring (securing compliance)– Record keeping – IRB approval…..

DOCUMENT IT!

• The rights, safety, and well-being of the trial subjects should prevail over interests of science and society.

• Freely given Informed Consent should be obtained from every subject prior to clinical trial participation.

• The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality

Federal Regulations21 CFR 50 – Human Subject Protection

• Specifies:– Consenting procedures– Elements to include in an informed consent– Documentation of informed consent– Exceptions of informed consent– Safeguards for children/wards

• Sponsor obligations:– Ensure informed consent process at site level is

compliant with regulatory requirements

DOCUMENT IT!

• IRBs – Institutional Review Boards (Ethics Committees) Review and approve research studies involving human subjects

• 21 CFR part 56 contains general standards for the composition, operation, and responsibility of an IRB that reviews clinical investigations regulated by the FDA

Federal Regulations21 CFR 56 - IRBs

An IRB has the authority to: • Approve research• Require modifications in research• Disapprove research• Require additional elements of informed consent

are provided• Waive the requirement for a signed informed

consent

• Sponsor’s obligations:– Ensure IRB is operating in compliance with 21 CFR 56– Ensure site is following IRB procedures

DOCUMENT IT!

• Protect the integrity and reliability of clinical data

• FDA considers whether adequate steps are taken in the design, conduct, reporting and analysis of studies to minimize bias

• The FDA works with the applicant/sponsor to minimize potential bias

Federal Regulations21 CFR 54 – Financial Disclosure

If financial interests raise questions about data integrity the FDA may:

• Initiate audits of the data from that investigator

• Request further analyses of data

• Request applicant to conduct additional studies

• Refuse the data

Investigator to Sponsor Sponsor to FDA

• Sponsor’s obligations:• Collect accurate investigator financial information before study

participation (21 CFR 812.43)• Report COI to FDA at time of application• Obtain updates throughout the study and for one year after all

study data is submitted

DOCUMENT IT!

• Describes How:– Electronic records, electronic signatures,

and handwritten signatures executed to electronic records are considered trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper.

Federal Regulations21 CFR 11 – Electronic Records

• To ensure the authenticity, integrity and confidentiality of electronic records, controls include:

– Tracking of data entry with an audit trail (paper or electronic)

– Documented verification of data entry accuracy

– Unique electronic signatures

• Sponsor’s obligation:– Know the requirements of 21 CFR 11– Ensure site and internal (sponsor) compliance

DOCUMENT IT!

• Statement of investigator’s commitment to:– Conduct the investigation in compliance with FAIR– Supervise device use– Obtain informed consent– Other items as agreed upon with sponsor…

Agreements

DOCUMENT IT!

• Inclusion / Exclusion

• Required Testing

• Procedural Requirements

• Randomization Processes

• Follow-up Requirements

Investigational Plan

DOCUMENT IT!

Requirements of IRB

• Informed consent procedures

• Adverse event reporting requirements

• Renewal timelines

• Etc.

Case Study #1

You are monitoring a site when you notice that an investigator routinely signs the consent forms days after the patients sign them. You’re not sure what to do. The manager of the brand new research coordinator tells you that this is no big deal and there is nothing to address.

She said “It’s not in the regs…..” Is she right?

Federal RegulationsAgreementsInvestigational PlanRequirements of IRB Could be specified by the IRB

Case Study #2A monitor notes that all of the IRB approvals were on file at a site, but some of the correspondence back and forth regarding the approvals was missing. The RC refused to locate the missing documentation.

The monitor insists “It’s in the Regs….” Is the monitor correct?

Federal Regulations

AgreementsInvestigational PlanRequirements of IRB

FDA requires that all correspondence with an IRB be maintained (21 CFR 812.140)

Case Study #3You have a site that routinely takes case report forms (CRFs) into the exam room while seeing patients. While much of the information you need for the study is included in the patient’s regular assessment, they write the other data directly onto the CRF. You think they need a separate source, but you’re not sure.

You dig into the regulations and find what???

Could be in an agreement

Could be in an investigational plan

Sandra MaddockCEO and President

John LehmanDirector of Business Development

Meet Our Team

Brandy SmithDirector of Clinical Monitoring Services

Mary LewisClinical Auditor

More Information for You

Download our Whitepapers

Drugs vs. Devices

• FDA’s official website:• www.fda.gov

• GCP Guidances and Information Sheets• http://www.fda.gov/oc/gcp/guidance.html

• Informed Consent• A Guide To Informed Consent:

• http://www.fda.gov/oc/ohrt/irbs/informedconsent.html• Protection of Subjects:

• http://www.fda.gov/cdrh/devadvice/ide/informed_consent.shtml• Running clinical trials

• http://1.usa.gov/ILt1tc

References

Sandra Maddock & Brandy Smith BioEnterprise Presentation 9.6.12

Health & Medicine