ICH Guidelines for Periodic Safety Update Reports (PSUR): Key Compliance Insights!

Periodic Safety Update Reports (PSURs) are important documents from a pharmacovigilance perspective, as these are meant to monitor the risk- benefit ratio of products at predetermined time intervals after authorization. These reports provide detailed comprehensive safety updates where all new or emergent risks are promptly addressed. The International Council for Harmonisation (ICH) developed the guidelines to outline the format, content, and submission timing of PSURs so that global safety reporting would be more uniform and efficient. Marketing authorization holders (MAH) must know and follow these guidelines to fulfill their legal responsibilities in areas of public health and safety of their products.

Objectives of PSURs:

The Main objective of PSUR is to present new or evolving safety information and scrutiny evaluation information of effectiveness, restriction of usage, and other alternatives pertinent to risk- benefit evaluation of the product being discussed. PSURs serve as a structured framework to compile data and aid regulators and MAHs to further:

• Determine if new safety data is available and how this new data aligns with the existing data.
• Reveal new safety concerns that could hinder the safety of clinical trial participants/ patients.
• Encapsulate in what ways risks are identified and currently managed and with what potential risks.
• Ascertain whether or not modifications need to be made to Reference Safety Information in order to enhance the ongoing safe use of the product.

ICH E2C(R2) Guidelines

1. Purpose: ICH E2C R2 provides a standard format on preparing the Ongoing Safety Evaluation-MS Periodic Reports known as PBRERs which integrates the safety and effectiveness of marketed drugs.
2. Focus Shift: It changes from case safety reports to an overall assessment of benefit risk, placing importance on the integration of data over time.
3. Content Structure: Guidelines identify and outline essential inclusions in PBRERs such as Marketing Authorization Worldwide, safety action taken, and other relevant clinical trials findings.
4. Harmonization: It seeks to style reporting across the ICH regions (EU, USA, Japan) which contributes toward uniformity in safety examined within different countries.
5. Implementation Support: This provision is covered by templates and Q&A documents accompanying the guidelines to help stakeholders determine their recommendations for compliance to the regulations.

PSUR in Pharmacovigilance

PSURs strengthen pharmacovigilance integration using a structured approach to protection against safety infringement after the product is marketed, thus helping to preemptively detect possible ongoing safety signals and applying appropriate risk alleviating measures. Here are the main highlights of a particular PSUR:

• DLP – Data Lock Point: This refers to a specific date that marks the point beyond which data cannot be altered, serving as the effective cut-off date for the data that will be presented in the report.
• Reporting Interval: This duration within the PSUR is specified in a range of 6 months to 3 years depending on the report and the drug’s risk profile.
• Reference Safety Information (RSI): The information that has been approved which new safety data is evaluated against.
• Summary of Safety Data: An overall of adverse events, clinical trial results, and post-marketing issues.
• Benefit-Risk Assessment: Evaluation of new safety information with regards to the overall benefits and risks of the drug.

PSUR Submission Timelines

Regulatory authorities have set many timelines for the submission of PSUR which MAHs must follow strictly. The European Medicines Agency (EMA) requires the following timelines:

• PSUR submissions for periods of up to 12 months is 70 days for points of data lock.
• For PSUR submissions exceeding 12 months, the EMA deadline is 90 days post data lock point.
• Ad hoc PSUR must be submitted within 90 days of the data lock point unless otherwise specified.

The MAHs are bound by law to the EURD list requirements which take precedence over standard submission cycles. Please note that the EURD list correspondents provide data points for freezing, submission dates, and rates for certain substances at the EU level.

Compliance and Submission Requirements

Compliance with guidelines and rules of ICH is very important for MAHs. For this reason, the following documents should be observed: 

• ICH E2C(R2) guideline along with other guidance documents.
• Submission timelines set by FDA and EMA must also be followed. 
• PSURS should be directly sent to the EMA by using the directed submission tool.
• In their submission, PSURs should be complete, profound, and make correct restorations on newly learned safety matters.
• Keep watching the EURD list in case something new is added or changes are made in the submission requirements.

Development Safety Update Reports (DSURs):

DSURs serve the same purpose as PSURs. DSURs are also prepared for new investigational drugs. DSURs encompass an annual assessment and analysis of safety data relevant to the drug, especially information that was collected within that reporting period. Although DSURs concern investigational drugs, there may be some overlap with PSUR scope, especially in terms of safety results from various clinical studies and trials.

Periodic Safety Update Reports FDA:

In the United States, the FDA utilizes the ICH guidance on PSURS in the regulatory approach. As per FDA regulations, the applicants are required to file postmarketing periodic safety reports in the formats of PADER/PAER or PSUR. For the first 3 years after grant of approval, these reports have to be submitted quarterly and yearly, subsequently. The FDA gives instructions with regards to how these reports should be formulated, paying attention to appreciation of ICH components and the corresponding US regulations.

Periodic Safety Update Reports in Pharmacovigilance:

PSURs are key in the maintenance of the marketing authorization in pharmacovigilance since they allow for a comprehensive review of the safety of the drug after it has been authorized. They facilitate the exchange of information between MAHs and regulatory authorities regarding specific new risks or additional benefit evaluation. Active monitoring is done to provide assurance that needed action is taken in time to protect public health.

Periodic Safety Update Reports Single Assessment:

The single assessment model offers a different approach for reviewing PSUR submissions. The model attempts to facilitate efficiency in reviewing the submissions by allowing several regulatory bodies to assess one submission instead of requiring each jurisdiction to be given a separate submission for individual assessment. This helps save time and effort for the MAHs while still ensuring strong safety monitoring.

Periodic Safety Update Reports for Marketed Drugs

Periodic Safety Update Reports are a vital component of pharmacovigilance that monitor safety for marketed drugs at set time intervals. These reports include a detailed review of a global database of safety information encompassing clinical trials, marketing, and post marketing adverse event reporting surveillance. The MAHs of a drug are obliged to provide the PSUR reports to the relevant authorities like European Medicines Agency or FDA as part of their mandatory post marketing safety activities. They assist with the discovery of previously undiscovered risks, changes in the existing benefit-risk profile delineation, and taking necessary action to protect the public’s health.

Periodic Safety Update Reports Medical Device

Though PSURs are most commonly related to pharmaceuticals, they cover medical devices as well under certain conditions. In Europe, it is now a requirement that manufacturers include PSURs in their post market surveillance obligations of the medical device. They are compilations of data outlining the performance of the device and its attendant adverse events over the period of device use to show continued adherence to safety compliance.

Periodic Safety Update Reports Guidance

Regulatory authorities issue documents guiding best practice for writing PSURs. These documents focus on simplicity, completeness, and compliance with deadlines. In addition, they stipulate content format requirements to include benefit-risk evaluation and summary of adverse events.

Conclusion:

Periodic Safety Update Reports (PSURs) are vital documents in the field of pharmacovigilance that contribute to drug safety in all stages of a product’s lifecycle. In complying with the guidelines by ICH and knowing the regulatory expectations set by the FDA and other bodies, MAHs can maximize their reporting duties and also protect the safety of the patients. With the continuous changes and development in technology and regulation, it is unquestionable that the PSUR life cycle best practices will always be relevant to the industry participants’ knowledge base.