Overview of ICH GCP

Question 1

Formed in the early 90s’ by representatives of the European Union, Japan and the United States.

Answer 1

The International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use, commonly referred to as the International Conference on Harmonisation

Question 2

In what year did the International Conference on Harmonisation become the International Council for Harmonisation

Answer 2

2015

Question 3

What is the goal of the ICH?

Answer 3

to standardize technical guidelines and requirements for drug marketing registrations, so that applications for marketing to various regulatory agencies around the world can occur without redundant testing.

Question 4

ICH E6 has become…

Answer 4

the international standard for the design, conduct, monitoring, and reporting of clinical research of investigational drugs.

Question 5

In what year was the ICH revised the E6 guideline to reflect the current research landscape, reflecting increases in globalization, study complexity, and technological capabilities? What were they entitled?

Answer 5

2016.

Integrated Addendum To ICH E6(R1): Guideline For Good Clinical Practice E6(R2)

Question 6

Legally Authorized Representative (LAR)

Answer 6

is an individual, or judicial or other body, authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research.

Question 7

Protocol Deviation (or Violation)

Answer 7

is generally an unplanned excursion from the requirements of the protocol that is not implemented or intended as a systematic change.

Question 8

Current ICH membership includes the following five (5) regulators.

Answer 8

1) Health Canada (Canada)
2) European Commission (European Union)
3) Ministry of Health Labor and Welfare/Pharmaceuticals and Medical Devices (PDMA from Japan)
4) Swissmedic (Switzerland)
5) Food and Drug Administration (USA)

Question 9

Current ICH membership also includes the following three (3) industry members:

Answer 9

1) European Federation of Pharmaceutical Industries and Associations (EFPIA from EU)
2) Pharmaceutical Research and Manufacturers of America (PhRMA from U.S.)
3) Japan Pharmaceutical Manufacturers Association (JPMA from Japan).

Question 10

The current ICH E6 expert working group includes:

Answer 10

1) Fourteen representatives from the six ICH founding members (four from U.S., four from EMA/EU, and six from Japan)
2) Two experts – one each from the two new ICH members Canada and Switzerland (Health Canada and Swissmedic joined the ICH Steering Committee in June 2014)
3) Four observers – one each from ANVISA (Brazil Sanitary Vigilance National Agency from Brazil), Department of Health (DoH of Chinese Taipei), Ministry of Drug and Food Safety (MFDS from South Korea), and World Self Medication-Industry (WSMI is a non-governmental organization [NGO] representing the self-medication industry)

Question 11

True or False: In the U.S. compliance with ICH E6 is voluntary, but as with any published FDA guidance, compliance is considered part of GCP.

Answer 11

True

Question 12

For sponsors, what is the advantage of complying with the ICH guideline?

Answer 12

the FDA and equivalent government agencies in other countries will consider studies conducted in accordance with ICH E6 to meet the regulatory requirements of the drug approval processes for all of these countries.

Question 13

ICH guidelines cover four (4) main categories and a letter of reference codes each category.

Answer 13

Q-Quality
S-Safety
E-Efficacy
M-Multidisciplinary

Question 14

Quality (Q) Topics

Answer 14

Those relating to chemical and pharmaceutical quality assurance

Question 15

Safety (S) Topics

Answer 15

Those relating to in vitro and in vivo preclinical research

Question 16

Efficacy (E) Topics

Answer 16

Those relating to research in human subjects

Question 17

Multidisciplinary (M) Topics

Answer 17

Topics that do not fit uniquely into one of the categories above

Question 18

The ICH E6 topic falls under the “Efficacy” category in the ICH guidelines and pertains specifically to…

Answer 18

the conduct of clinical research to support marketing applications for drugs. It provides a unified standard for designing, conducting, recording, and reporting research involving human subjects.

Question 19

The two important goals of ICH E6 are to assure that:

Answer 19

1) The rights, well-being, and confidentiality of trial subjects are protected
2) Trial data are credible

Question 20

The principles of ICH GCP as presented in ICH (2016) E6 are: (13)

Answer 20

1) Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).
2) Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.
3) The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.
4) The available nonclinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.
5) Clinical trials should be scientifically sound, and described in a clear, detailed protocol.
6) A trial should be conducted in compliance with the protocol that has received prior Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approval/favourable opinion.
7) The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.
8) Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).
9) Freely given informed consent should be obtained from every subject prior to clinical trial participation.
10) All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification. This principle applies to all records (paper or electronic) referenced in this guideline.
11) The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
12) Investigational products should be manufactured, handled, and stored in accordance with applicable Good Manufacturing Practice (GMP). They should be used in accordance with the approved protocol.
13) Systems with procedures that assure the quality of every aspect of the trial should be implemented.

Question 21

Investigators participating in clinical research take on specific obligations: (9)

Answer 21

1) qualifications
2) resources
3) medical care of research subjects
4) interactions with IRBs/IECs
5) compliance with protocols
6) management of investigational products
7) informed consent of subjects
8) record keeping
9) reporting

Question 22

If the investigator/institution retains the services of any party to perform study tasks they should…

Answer 22

ensure this party is qualified to perform those study tasks and should implement procedures to ensure the integrity of the study tasks performed and any data generated.

Question 23

The investigator is responsible for supervising…

Answer 23

any individual or party to whom the investigator delegates study tasks conducted at the trial site.

Question 24

Who must implement a quality management system throughout the design, conduct, recording, evaluation, reporting, and archiving of clinical trials

Answer 24

The Sponsor

Question 25

The ICH E6 guideline recommends the quality management system use?

Answer 25

A risk-based approach

Question 26

Although a sponsor may transfer any or all of their responsibilities and functions to a Contract Research Organization (CRO), the sponsor should...

Answer 26

ensure oversight of the CRO and specify in writing what responsibilities are transferred.

Question 27

Sponsor responsibilities include: (11)

Answer 27

1) quality management 2) quality assurance and control 3) trial design 4) trial management 5) investigator selection 6) compensation to subjects and investigators 7) confirmation of review by IRB/IEC 8) supplying and handling the investigational product 9) adverse drug reaction reporting 10) monitoring 11) auditing

Question 28

Content standards for clinical trial protocols: (11)

Answer 28

1) selection and withdrawal of subjects 2) treatment of subjects 3) safety and efficacy assessment 4) statistics 5) direct access to source data/documents 6) quality control and assurance 7) ethics 8) data handling and recordkeeping 9) financing and insurance 10) publication policy 11) supplements.

Question 29

True or False: ICH E6 is codified in U.S. federal regulation and carries the same legally binding weight of the code of federal regulations.

Answer 29

False.

Question 30

what is the 21 CFR 50?

Answer 30

Protection of Human Subjects FDA regulation

Question 31

what is the 21 CFR 56?

Answer 31

Institutional Review Boards FDA regulation

Question 32

True or False: ICH E6 allows broader access to research records and to otherwise confidential medical records than is required by FDA regulations.

Answer 32

True Note: If investigators are required to comply with ICH, they must clearly disclose this information to subjects during the informed consent process.

Question 33

True or False: The ICH E6 guideline generally requires more from the sponsor than the FDA does.

Answer 33

True Examples: ICH E6 Section 5.11 requires the sponsor to obtain from investigators/institutions a statement from their IRB/IEC that the IRB/IEC is organized and operates according to GCP and the applicable laws and regulations. ICH E6 Section 5.15.2 requires the sponsor to verify that each subject has consented, in writing, to direct access to his/her original medical records for trial-related monitoring, audit, IRB/IEC review, and regulatory inspection. The FDA does not have comparable requirements.

Question 34

ICH (2016) E6 Section 1.26 defines an impartial witness as

Answer 34

a person who is independent of the trial, who cannot be unfairly influenced by people involved in the trial, who attends the informed consent process if the subject or the subject's legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject.

Question 35

True or False: According to ICH E6, an impartial witness can be used when a subject (or subject's LAR) can read.

Answer 35

False

Question 36

True or False: If the subject can read in their native language, but not in English, the consent form must be provided in a language that the subject can read and understand.

Answer 36

True

Question 37

The agreement of someone who cannot consent for his or herself is called

Answer 37

Assent

Question 38

True or False: Both the FDA & ICH E6 Section 4.8.12 requires assent of those adults capable of providing assent, along with the permission from their LARs.

Answer 38

False, FDA does not.

Question 39

True or False: With a few exceptions, ICH E6 Section 4.8.13 also requires that only subjects who are able to consent for themselves be allowed to enroll in non-therapeutic research studies (a trial in which there is no anticipated direct clinical benefit to the subject)

Answer 39

True Exceptions include studies with all of the following: The study objectives cannot be met without including these subjects. The foreseeable risks to the subjects are low as is the negative impact. The study is not illegal. The IRB has specifically agreed to include these subjects.

Question 40

According to ICH E6, the IRB/IEC is required to review specific documents: (9)

Answer 40

1) Written informed consent form(s) and consent form updates that the investigator proposes for use in the trial 2) Trial protocol(s)/amendment(s) 3) Subject recruitment procedures (advertisements) 4) Written information to be provided to subjects 5) Investigator's Brochure (IB) 6) Available safety information 7) Information about payments and compensation available to subjects 8) The investigator's current curriculum vitae and/or other documentation evidencing qualifications 9) Any other documents that the IRB/IEC may require to fulfill its responsibilities

Question 41

Set the standard for the design, conduct, monitoring, and reporting of clinical research.

Answer 41

GCP

Question 42

The ICH GCP guidelines do not address certain ethical requirements that are found in the Declaration of Helsinki (DOH), such as: (5)

Answer 42

1) The use of placebo versus standard therapy 2) Post-study access to treatment and other benefits for subjects 3) Public disclosure of study design 4) Publication of study results 5) Disclosure of conflicts of interests