Good Clinical Practice: A Question and Answer Guide2024/2025 Edition - 167

Clinical Trial Protocols/Protocol Changes/Protocol Violations
authorities- Guidance for Use in Emergencies. These essential guidance documents provide a clear framework for
requesting and implementing EUAs for medical products during public health emergencies. It is essential to refer
to the full guidance document and consult with the FDA for specific details and updates related to EUAs. Eligibility
for EUA must be met for a medical product to be considered for EUA including the existence of a serious or lifethreatening
condition and the absence of approved alternatives. Data must be submitted to the agency in advance
of use such as preclinical and clinical data, manufacturing information and labeling. Emergency use authorization
determination is a rigorous process and may be expedited. Informed consent requirements are outlined as well
as labeling requirements, the sponsors obligation to monitor adverse events and submission of safety data. Please
note that regulations and guidance related to EUAs may evolve, and new guidance documents may be issued by
the FDA in response to specific emergencies. It is essential to refer to the FDA's official website or consult with
the FDA directly for the most up-to-date information and guidance on Emergency Use Authorizations and related
regulations. Additionally, the COVID-19 pandemic has led to the issuance of specific guidance related to EUAs
for COVID-19 products.
Currently, several FDA documents (other than the FDA regulations mentioned above) apply to emergency
research:
Information Sheet titled " Exception from Informed Consent for Studies Conducted in Emergency Settings:
Regulatory Language Excerpts from Preamble. " (Updated January 15, 2016) [https://www.fda.gov/
RegulatoryInformation/Guidances/ucm126482.htm]
November 2014 CDER Manual of Policies and Procedures (MAPP) 6030.8 Rev.1
6.18 Q. Are there any specific requirements related to studies involving geriatric subjects?
A. There are no specific regulations or requirements related to the conduct of a study of geriatric subjects in clinical
trials. The FDA NDA regulations do require that the label for a product contain sufficient number of subjects aged
65 and over to determine whether elderly subjects respond differently than younger subjects (201.57(8)(v)). This
means that any drug that will likely be used in elderly subjects be studied in geriatric subjects. The exact number
of subjects needed for an adequate sample is not specified and is individualized for each drug and therapeutic area.
The FDA also recommends the use of the ICH E7 guidance on geriatric studies be consulted. Finally, the EMA has
issued a working paper on " Medical Research for and with Older People in Europe " in 2013 that addresses clinical
trial considerations in the elderly.
6.19 Q. How does the ICH E6 (R3) Draft requirement for quality management and risk assessment affect
protocol development and future amendments?
A. ICH E6 (R3) Draft, the International Council for Harmonization's guideline for Good Clinical Practice (GCP),
places a strong emphasis on quality management and risk assessment throughout the conduct of clinical trials.
These principles have implications for protocol development and future protocol amendments. ICH E6 (R3) Draft
promotes four main elements throughout the protocol development and future protocol amendments. The ICH E6
(R3) Draft promotes Proactive planning of protocols with a focus on identifying and mitigating potential risks
from the outset. Ongoing risk assessment throughout the trial which may lead to protocol amendments to address
unforeseen issues. The point that decisions should be data driven and that protocol amendments are developed based
on systematic data collection and analysis. And lastly the fact that both the initial protocol design and amendments
should prioritize patient safety and data integrity, ensuring that any changes are justified and beneficial.
ICH E6 (R3) Draft examines protocol development and future protocol amendments. For protocol development
R3 encourages a risk-based approach, meaning that sponsors and investigators should identify and assess potential
risks associated with the trial and incorporate risk mitigation strategies into the protocol. These risk mitigation
strategies should consider factors that may impact the quality and integrity of the trial, including risks related to
subject safety, data quality and regulatory compliance. The protocol should incorporate measures to mitigate these
risks. The guideline emphasizes the importance of avoiding unnecessary protocol complexity and that the protocol
should be clear, concise, and focused on the essential elements needed to achieve the trial objectives. Lastly
protocols should be scientifically sound and designed to generate reliable and meaningful data. Risk assessment
during the protocol development should address factors that could impact the scientific validity of the clinical trial.
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Good Clinical Practice: A Question and Answer Guide2024/2025 Edition

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