What is the Periodic Safety Update Report?

Periodic safety update reports (PSUR) A Periodic Safety Update Report (PSUR) is a pharmacovigilance document intended to provide an update of the worldwide safety experience of a medicinal product to regulatory authorities at defined time points post-authorisation.

The objective of the PSUR is to present a comprehensive and critical analysis of the risk-benefit balance of the product taking into account new or emerging safety information in the context of cumulative information on risk and benefits. This evaluation should ascertain whether further investigations need to be carried out and whether changes should be made to the product information or marketing authorisation.

Examples of sources of efficacy, effectiveness and safety information that may be used in the preparation of PSURs include:

data from clinical and non-clinical studies; spontaneous reports (e.g. on the marketing authorisation holder’s safety database); product usage data and drug utilisation information; observational studies, including registries; scientific literature.

The format of the PSUR follows the structure described in the Implementing Regulation Article 35 and Module VII of the provides guidance on the preparation, submission and assessment of PSURs. This format is a legal requirement for all products, regardless of the legal basis.

• PSUR submissions are not required for all medicinal products, but the need for PSURs is determined using a risk-based approach.
• Certain products authorized under certain legal basis are exempted to submit PSURs routinely (Article10.1 generic, Article 10a well-established use, Article 14 homeopathic and Article 16 traditional herbal medicinal products).

For such products, PSURs shall be submitted only where there is a condition in the marketing authorisation or when requested by a competent authority. The PSUR submission frequency is variable. Marketing Authorisation Holders (MAHs) are required to submit PSURs according to the data lock points published in the EURD list.

• The EURD list is legally binding.
• The EURD list is a living document which will be amended whenever considered necessary by the PRAC, the CHMP or CMDh in response to the emergence of relevant new safety information, newly authorised substances and requests received from MAHs.
• Substances can be added or removed as appropriate.

The EURD list is updated on a monthly basis; MAHs should therefore maintain an awareness of the current status of the list. PSURs shall also be submitted at any time immediately upon request by the regulatory authorities.

What is PSUR and DSUR?

Manager| Pharmaceutical| Regulatory Affairs| New Product Development |Consumer products| Multivitamins| Medical devices| Food Supplements| Business Development | Managing teams| Contract manufacturing organizations – Published May 30, 2023 The DSUR (Development Safety Update Report) and PSUR (Periodic Safety Update Report) are both pharmacovigilance documents related to the safety monitoring of pharmaceutical products, but they differ in their purpose and timing of submission.

Purpose:

• DSUR: The DSUR focuses on providing safety updates and evaluations during the development stages of a medicinal product. It is typically submitted to regulatory authorities at defined intervals during clinical trials and may continue post-marketing until the product’s marketing authorization is obtained.
• PSUR: The PSUR is a comprehensive safety report that provides a periodic assessment of the safety profile of a marketed medicinal product. It covers the post-authorization phase and is submitted to regulatory authorities at defined intervals according to regulatory requirements.

Timing:

• DSUR: The DSUR is submitted during the development stages of a medicinal product, starting from early clinical trials until marketing authorization is obtained. It is typically submitted at regular intervals, often annually or more frequently, depending on the specific regulatory requirements.
• PSUR: The PSUR is submitted after the product has received marketing authorization and is available on the market. The timing of PSUR submissions is determined by regulatory guidelines and can range from every six months to annually or longer, depending on the product’s characteristics and regulatory requirements.

Scope:

• DSUR: The DSUR primarily focuses on safety data collected during the product’s development stages, including clinical trials. It provides an overview of adverse events, serious adverse events, safety concerns, and the benefit-risk assessment based on available data.
• PSUR: The PSUR covers a broader safety assessment, encompassing data collected from post-marketing sources, such as spontaneous adverse event reporting, literature, and other relevant sources. It includes a more extensive analysis of safety data and provides an updated benefit-risk assessment of the product.

Regulatory Requirements:

• DSUR: The submission of DSURs during the development stages is often required by regulatory authorities to ensure ongoing safety monitoring and evaluation of the investigational product. Specific requirements and guidelines may vary depending on the regulatory jurisdiction.
• PSUR: The submission of PSURs is a regulatory requirement for marketed products in most regions. Regulatory authorities typically provide guidelines on the content, format, and submission timelines for PSURs.

It’s important for pharmaceutical companies to adhere to the specific regulatory guidelines and requirements for both DSUR and PSUR submissions to ensure comprehensive safety monitoring, assessment, and reporting throughout the development and post-marketing phases of their medicinal products.

What are the objectives of a Periodic Safety Update Report?

The MAH should submit a PSUR within 60 days of the data lock point. An objective of a PSUR is to establish whether information recorded during the reporting period is in accord with previous knowledge on the drug’s safety, and to indicate whether changes should be made to product information.

What is the Periodic Safety Update Report as a pharmacovigilance tool?

Abstract – The periodic safety update report for marketed drugs (PSUR) was designed to be a stand-alone document that allows a periodic but comprehensive assessment of the worldwide safety data of a marketed drug or biological product. The PSUR can be an important source for the identification of new safety signals, a means of determining changes in the benefit-risk profile, an effective means of risk communication to regulatory authorities and an indicator for the need for risk management initiatives, as well as a tracking mechanism monitoring the effectiveness of such initiatives.

• For these reasons, the PSUR can be an important pharmacovigilance tool.
• Numerous steps are involved in the PSUR process including: intake of adverse drug reaction information, case processing, data retrieval, data analysis, and medical review and risk assessment.
• These processes are heavily reliant on the availability of adequate resources.

An overarching principle throughout the PSUR process is the need for a proactive approach in order to identify the critical steps in the process and to have a clear understanding of the consequences of any critical ‘mis-step’. With this information comes appropriate planning, building quality into each step of the PSUR process and monitoring performance will maximise the likelihood of generating a quality report.

Any failure of a key PSUR process will have the opposite effect – a poor quality report that will give little insight into emerging safety signals or provide misleading information that can adversely affect public health. A pragmatic approach that will avoid or minimise these pitfalls includes the following: adequate resource planning, training, development of ‘scripts’ designed to maximise the capture of key information for medically important reactions, standardised and harmonised Medical Dictionary for Regulatory Activities (MedDRA) coding procedures, pre-specified search criteria for data retrieval, ongoing medical review, and metrics to evaluate the effectiveness and efficiencies of these processes.

With these quality measures in place, the utility of the PSUR as an effective pharmacovigilance tool is enhanced.

What is the purpose of PSUR?

This page includes information on periodic safety update reports (PSURs), PSUR submission requirements, PSUR single assessment procedures (PSUSAs) and the European Union reference dates (EURD) list. PSURs are pharmacovigilance documents intended to provide an evaluation of the risk-benefit balance of a medicinal product at defined time points after its authorisation.

The objective of the PSUR is to present a comprehensive and critical analysis of the risk-benefit balance of the product, taking into account new or emerging safety information in the context of cumulative information on risk and benefits EMA and national competent authorities assess information in PSURs to determine if there are new risks identified for a medicine and/or if its risk-benefit balance has changed.

A PSUR assessment can determine if further investigations on a specific issue are needed, or if an action is necessary to protect public health (e.g. an update of the information provided to healthcare professionals and patients). Marketing authorisation holders (MAHs) are legally required to submit PSURs, in line with Regulation (EU) No 1235/2010, Directive 2010/84/EU and Commission Implementing Regulation (EU) No 520/2012, Module VII of the Guidelines on Good Pharmacovigilance Practices (GVP) provides guidance on the preparation, submission and assessment of PSURs. This format is a legal requirement for both nationally authorised products and centrally authorised products,

What is the difference between PMS report and PSUR?

What’s the Difference Between a PSUR and a PMSR? – The PMSR is intended for low-risk Class I devices. It needs to summarize the results and conclusions of your postmarket surveillance (PMS) data that you defined in your PMS plan (see MDR Article 84 and Annex III for more details about this document) along with a rationale for and description of any preventive and corrective actions taken for products on the market.

• This report becomes part of your technical documentation and is updated as needed and made available to EU Competent Authorities upon request.
• The PSUR is required for Class IIa, IIb, and III devices.
• The PSUR is essentially an extension of a PMSR containing additional information for higher-risk devices.

Like the PMSR, it summarizes the results and conclusions from your PMS data that you defined in the PMS plan and includes a rationale and description of any corrective actions taken for product on the market. The other specific required contents of this report are outlined in Article 86 of the MDR.

Conclusions of benefit-risk determination Main findings of your postmarket clinical follow-up (PMCF) Volume of devices placed on the market (this can be volume of sales, units shipped, episodes of use for reusable devices, etc.) Estimates of size or other characteristics of people using the device (plus usage frequency if known)

You’ll find extensive information about the PSUR requirements in MDCG 2022-21, so be sure to download this.

What is the difference between PMSR and PSUR?

Post Market Surveillance Report (PMSR) – The PMSR is very similar to the PSUR—it is also meant to summarize results and conclusions from your postmarket surveillance, and it also includes the rationale for, and description of, any CAPAs. However, there are some key differences:

The PMSR is required for Class I medical devices and IVDs in Class A and B. Essentially, the PSMR is for low-risk devices and the PSUR is for those with a moderate or high risk. Your PMSR must be maintained and available to EU Competent Authorities upon request, but it does not need to be submitted on a regular basis. The MDR recommends updating your PMSR at least once every three years.

When should DSUR be submitted?

A DSUR must be submitted during every 12-month reporting period until the End of Trial Notification has been submitted to the competent authority of the member state where the trial is being conducted.

Is the ASR and DSUR the same?

DSURs are internationally-harmonized safety documents (mandatory in European Union member states since September 2011) covering the safety summary of medicinal products during their development or clinical trial phase.The DSUR (defined in guideline ICH E2F) replaced the previous European Union ASR (Annual Safety Report) and the United States IND Annual Report.Sponsors are required to submit a DSUR within one year of the Development International Birth Date (DIBD – the date of first authorisation of a clinical trial in any country worldwide) and provide annual DSUR submissions until all open clinical studies have ended (the final clinical study is completed and its study report has been submitted).Trilogy is well placed to support our clients in all elements of DSUR and other safety document development.Trilogy can also arrange full clinical review and sign-off, as well as published literature summary and analysis, and provide suggestions for company comments.

How often should PSUR be updated?

Frequency of Submitting a PSUR – The frequency of submitting a PSUR depends on the regulatory classification of your medical device and the stage at which the development and marketing of the device are. For instance, for approved medical devices that have yet to be released to the market, you must submit a PSUR at least every six months after authorization until you place your medical device on the market.For devices that are already on market on the other hand, submission frequency is either at least every 2 years, or at least every 1 year, depending on the regulatory class.

The same is true for IVDR products. A report that covers the period during which the device is launched is considered to be the last of the six-month PSURs you’re required to submit before the “preliminary placement of the product on the market.” Note that the date of your initial placement should fall after the European Birth Date (EBD).

After the initial placement of your medical devices on the market, the subsequent PSURs should be submitted after six months for the first two years, annually for the subsequent two years, and every two years thereafter. For devices on a six-month submission schedule, you can submit a request to the regulator or NB to move your submissions to annually if you want them to align with your EU signal detection submissions.

You should submit your PSURs immediately if the VMD requests them on an ad hoc basis. Fortunately, you can agree with the regulator on the appropriate Data Lock Point (DLP) and submissions date, based on how urgently they need the report. A different submission schedule may be set, especially when you’re requesting marketing authorization as a condition for approval, or because of serious safety concerns discovered during marketing.

For medical devices already on the market, the MDR requires PSUR submissions according to device risk class. Class IIa devices must submit a PSUR during Notified Body Conformity Assessment reviews. Class IIb non-implantable devices must also submit a PSUR during Notified Body Conformity Assessment reviews; however this must occur at least every 1 year.

Class IIb implantable and Class III products must also submit a PSUR at least every year; however these PSURs can be submitted via EUDAMED, for Notified Body review. For IVDR products, the requirements are similar. Class C IVDRs must submit a PSUR at least every year during Notified Body Conformity Assessment reviews.

Class D IVDRs must also submit a PSUR at least every year; however they can be submitted via EUDAMED for Notified Body review.

What is PSUR for medical devices?

The Periodic Safety Update Report in the Medical Devices Regulation (MDR) – The MD world is not used to PSURs, it is a new feature of the MDR stated in Article 86 : Manufacturers of class IIa, class IIb and class III devices s hall prepare a periodic safety update report (PSUR) for each device and where relevant for each category or group of devices summarising the results and conclusions of the analyses of the post-market surveillance data gathered as a result of the post-market surveillance plan referred to in Article 84 together with a rationale and description of any preventive and corrective actions taken.

The PSUR summarizes the outcome of the post-marketing surveillance activities, setting out conclusions on the indicators followed and on the significant events found. These events may be already identified and already followed up, they may also be new : new risks, or benefits ultimately not achieved.

The surveillance objectives depend on the results of design & development, of risk management and clinical evaluation activities, the PSUR thus aims to demonstrate that the benefit/risk ratio remains favorable during market phase.

What is the full form of DSUR?

Development Safety. Update Report (DSUR)

What is meant by DSUR in pharmacovigilance?

What is a DSUR? The development safety update report (DSUR) is pre-marketing periodic report which covers safety information of drugs, biological, vaccines and combo products under development (including marketed drugs that are under further study) among the ICH regions.

1. All indications
2. All dosage forms
3. All intended populations

For combined products: A single DSUR should be prepared for clinical trials involving a fixed combination product (i.e., a product consisting of at least two active ingredients in a fixed dose that is administered in a single dosage form). If the sponsor is also conducting clinical trials with individual component(s) of the fixed combination product, separate DSUR(s) should be submitted for each component.

• examining whether the information obtained by the sponsor during the reporting period is in accord with previous knowledge of the investigational drug’s safety
• describing new safety issues that could have an impact on the protection of clinical trial subjects
• summarizing the current understanding and management of identified and potential risks
• providing an update on the status of the clinical investigation/development program and study results.

The DSUR includes safety information of active moiety from:

1. All ongoing clinical trials and other studies that the sponsor is conducting or has completed during the review period
2. Observational or epidemiological studies
3. Nonclinical studies (toxicological and in vitro studies)
4. Related DSURs, if applicable to the investigational drug
5. Manufacturing or microbiological changes
6. Studies recently published in the literature
7. Clinical trials with results indicating lack of efficacy that could have a direct impact on subject safety (e.g., worsening of the underlying condition if the indication is serious or life-threatening)
8. Any other source of relevant safety findings for products in the same therapeutic class
9. Clinical trials conducted by a co-development partner, if permitted by the contractual agreement.

When to submit DSUR: There is a single, harmonized Developmental International Birthdate (DIBD) which is the first authorization from a regulatory agency to the sponsor to do a clinical trial anywhere in the world. This will require the regulatory group in the company to convey this information to all of the involved health agencies so that the birthdate is harmonized.

1. Since there is a known fixed schedule for submission, there will be a fixed, single data lockpoint 60 days before submission for each DSUR.
2. In most countries the DSUR is submitted annually.
3. Companies that have open INDs and NDAs (or the ex-US equivalents such as CTCs/CTXs and MAs respectively) may also have their regulatory departments harmonize the birthdate for DSURs and PSURs such that there is a single submission date.

DSUR and PSUR: When clinical trials continue after receiving market approval, both DSUR and PSUR are needed separately. DSUR data lock point (DIBD) can coincide with the International Birth Date (IBD) if desired by sponsor. Recipients of DSUR

• Regulatory Authorities: DSUR; within 60 days from the DIBD
• EC/IRB, if required: Executive Summary (plus line listing of SADRs)
• Final DSUR in a Territory: will be notified with a cover letter.

DSUR Contents Title page Executive Summary Table of Contents

1. Introduction
2. Worldwide Marketing Approval Status
3. Actions Taken in the Reporting Period for Safety Reasons
4. Changes to Reference Safety Information
5. Inventory of Clinical Trials Ongoing and Completed during the Reporting Period
6. Estimated Cumulative Exposure
   • 6.1 Cumulative Subject Exposure in the Development Program
   • 6.2 Patient Exposure from Marketing Experience
7. Data in Line Listings and Summary Tabulations

• 7.1 Reference Information
• 7.2 Line Listings of Serious Adverse Reactions During the Reporting Period
• 7.3 Cumulative Summary Tabulations of Serious Adverse Events

8. Significant Findings from Clinical Trials during the Reporting Period

• 8.1 Completed Clinical Trials
• 8.2 Ongoing Clinical Trials
• 8.3 Long-term Follow-up
• 8.4 Other Therapeutic Use of Investigational Drug
• 8.5 New Safety Data Related to Combination Therapies

9. Safety Findings from Noninterventional Studies 10. Other Clinical Trial/Study Safety Information 11. Safety Findings from Marketing Experience 12. Nonclinical Data 13. Literature 14. Other DSURs 15. Lack of Efficacy 16. Region-Specific Information 17. Late-Breaking Information 18. Overall Safety Assessment

• 18.1. Evaluation of the Risks
• 18.2 Benefit-riskConsiderations

19. Summary of Important Risks 20. Conclusions Appendices to the DSUR When to stop submitting a DSUR? In Europe an annual safety report is to be submitted throughout the clinical trial (CT) to Member States in whose territory the CT is being conducted (Clinical Trial Directive 2001/20 Article 17(2)).

• Generally speaking, the submission should stop when the trial ends.
• However there seems to be 3 different interpretations: • The definition of a completed trial for DSUR purposes is given in the ICH E2F glossary: ‘Study for which a final clinical study report is available is a completed clinical trial.

For DSUR purposes a trial for which enrolment has begun and a final clinical study report is not available, is considered to be ongoing.’ This would mean a DSUR needs to be submitted to the concerned member states (MS)s until the final clinical study report is completed and its summary submitted to these European MSs.

• According to CT1 (2.5), the end of CT is to be defined clear and unambiguous in the protocol.
• In most cases it will be the date of last visit of last patient.
• CT‐3 guidance paragraph 126 reads: ‘The report should only be submitted to the national competent authority and the Ethics Committee if the treatment of subjects is ongoing in that Member State concerned.’ Meaning that DSUR is to be submitted until the end of treatment of the last subject in the MS concerned.

In order to harmonise ICH E2F, CT1 and CT3, the interpretation of the ‘treatment of subjects is ongoing’ is that this clinical trial has not ended yet. Therefore, a DSUR should be submitted until the last visit of the last patient in the MS concerned, as specified within the protocol.

And a DSUR should only be submitted to the concerned MS(s) on which’s territory the clinical trial has not ended yet, no submission in needed to the concerned MS(s) where the clinical trial ended already. In the case of multiple studies being authorised by the concerned MS within the reporting period, a DSUR must be submitted until the last open CT has come to an end (LVLP) in this concerned MS.

The DSUR is a more or less harmonized document now accepted in most of the countries of the world. It is a more complex and analytical document than the old style annual safety reports.

What is PMS and PSUR?

Please fill the form to download – Post Market Surveillance Report (PMSR) and Periodic Safety Update Report (PSUR) compose critical documentation of Post Market Surveillance (PMS) of a Medical Device and an In-Vitro Diagnostic Device (IVD). Medical Device and IVD manufacturers with an intent to market the products in the European Union (EU) shall comply with Medical Device Regulation (EU MDR) 2017/745 and In-Vitro Diagnostic Regulation (EU IVDR) 2017/746.

• Post Market Surveillance, commonly called as PMS, is one such compliance requirement applicable for manufacturers of all device classes and is covered under Articles 83-86 of MDR and Articles 78 – 81 of IVDR.
• The information, frequency, and submission requirements for PMSR and PSUR vary based on the device class.

The manufacturers of Low-risk Class I Medical Devices and Class A, B In-Vitro Diagnostics (IVDs) should maintain a Post Marketing Surveillance Report (PMSR). The PMSR need not be submitted to any authority for CE Certification of the device. This report should be compiled, updated periodically, and shall be readily available for submission to the competent authority upon request.

• The manufacturers of moderate and high-risk Class IIa, IIb, III Medical Devices and Class C, D In-Vitro Diagnostics (IVDs) should submit Periodic Safety Update Report (PSUR).
• PSUR must be submitted to Competent Authority or Notified Body as a part of technical documentation.
• The PSUR document is evaluated as part of Conformity Assessment.

The PMSR shall contain summary of results and conclusions derived from analysis of PMS data collected as per the PMS plan. It should also describe the Preventive and Corrective actions taken. The PSUR, on the other hand, shall summarize the results and conclusions derived from the analysis of Vigilance, PMS, and PMCF data collected as per the PMS Plan.

the conclusions of the benefit-risk determination the main findings of the Medical Device Post-Market Clinical Follow-up (PMCF) or IVD’s Post-Market Performance Follow-up (PMPF) the volume of sales of the device and an estimated evaluation of the size and other characteristics of the population using the device, and, where applicable, the usage frequency of the device

The Reports (PMSR and PSUR) are to be prepared and updated throughout the lifetime of the device. The PMSR shall be updated as and when any new changes are made to the Class I Medical Device or Class A, B IVDs in scope. The PSUR for Class IIa devices shall be updated as and when required and at the least once in every two years.

What is a DSUR in pharmacovigilance?

Development Safety Update Report (DSUR) A Development Safety Update Report (DSUR) gives safety information relating to drugs under clinical development. The purpose of the DSUR is to present a comprehensive, annual review and evaluation of pertinent safety information collected during the reporting period related to a drug under investigation, whether or not it is marketed.

The DSUR should be concise and provide information to assure regulators that sponsors are adequately monitoring and evaluating the evolving safety profile of the drug under investigation. Local formats are often still submitted instead of these reports (eg, Periodic Adverse Drug Experience Report in the United States).

It is written annually, starting from the development international birth date (ie, the sponsor’s first authorization to conduct a clinical trial in any country), for as long as the sponsor conducts clinical trials with the investigational product or for as long as indicated by regional or national laws or regulations.

The data lock point (DLP) marks the end of the 1-year DSUR reporting period and is the cut-off date for data in the DSUR. The DSUR is a pharmacovigilance document with a strict and non-negotiable regulatory deadline and requires content and data from several contributors. In this regard, communication and time management are extremely important to finish the document in a timely and efficient manner.

The Medical Writer’s role is crucial in planning, managing, and writing of the document. It is key to keep this document short and concise and to ensure consistency across all DSUR sections and also across different pharmacovigilance documents (DSUR, RMP, PSUR/PBRER).

Who is responsible for submitting PSUR?

1. Introduction – A Periodic Safety Update Report (PSUR) is an important document provided by the Marketing Authorisation holder (MAH) to the VMD at defined time points post-authorisation. The document is intended to provide an update of the worldwide safety experience of a product, including a summary of all adverse events received during the period covered by the document and a critical evaluation of the benefit-risk balance of the product.

This evaluation should determine whether further investigations need to be carried out and/or whether changes should be made to the product information. PSURs are required regardless of whether or not a product has been marketed; but an abridged version as detailed below, in the PSUR content section, will be accepted.

Electronic copies of PSURs, including line listings, should be submitted to the VMD using the VMD’s digital services. The VICH have produced a guideline Topic GL 29 “Pharmacovigilance of Veterinary Medicinal Products – Management of Periodic Summary Update Reports (PSURs) which describes the management of PSURs.

Does FDA require PSUR?

Understanding PSURs: A Guide to Periodic Safety Update Reports Periodic Safety Update Reports (PSURs) are critical documents for medical device and in vitro diagnostic product manufacturers. These reports are a key component of a manufacturer’s post-market surveillance and risk management program, providing ongoing assessment of the safety and performance of their products. A PSUR is a comprehensive report that provides an evaluation of the safety and performance of a medical device or in vitro diagnostic product over a defined period of time. The report summarizes the manufacturer’s post-market surveillance activities, including adverse event reporting, complaint handling, and other sources of safety information.

Executive Summary: This section provides a brief overview of the report’s content and findings. Introduction: This section provides background information on the product, including its intended use, regulatory status, and any significant changes since the previous PSUR. Pharmacovigilance Activities: This section describes the manufacturer’s post-market surveillance activities, including adverse event reporting, complaint handling, and other sources of safety information. Safety Evaluation: This section summarizes the safety data collected during the reporting period, including any adverse events, trends, and emerging safety concerns. Benefit-Risk Assessment: This section evaluates the product’s risk-benefit balance based on the safety and effectiveness data collected during the reporting period. Conclusion and Recommendations: This section provides a summary of the report’s findings and any recommendations for further action.

The regulatory requirements for PSURs vary depending on the jurisdiction and the type of product. In the European Union (EU), PSURs are required for all medical devices and in vitro diagnostic products that have received a CE mark. The frequency of PSUR submission depends on the classification of the product, with higher-risk products requiring more frequent reporting. The process for preparing and submitting PSURs involves several steps, including:

Data Collection: The manufacturer collects safety and performance data for the reporting period, including adverse events, complaint handling, and other sources of safety information. Data Analysis: The manufacturer analyses the data to identify any safety concerns or emerging trends. Report Writing: The manufacturer prepares the PSUR, including an executive summary, introduction, safety evaluation, benefit-risk assessment, and conclusions. Internal Review: The manufacturer conducts an internal review of the PSUR to ensure its accuracy and completeness. Submission: The manufacturer submits the PSUR to the regulatory authority or notified body, as required.

To ensure the accuracy and completeness of PSURs, manufacturers should follow some best practices, including:

Establishing a robust post-market surveillance program that includes the collection and analysis of safety and performance data. Conducting regular internal reviews of safety data to identify emerging safety concerns. Ensuring that all adverse events and complaints are reported in a timely manner to the regulatory authority or notified body. Designing PSURs to be comprehensive and transparent, with clear and concise Involving cross-functional teams in the preparation of PSURs, including representatives from regulatory affairs, clinical development, and quality assurance. Providing a clear and detailed description of the product and its intended use, as well as any significant changes since the previous PSUR. Ensuring that the safety evaluation and benefit-risk assessment sections are based on robust data and analysis and that any limitations or uncertainties are clearly communicated. Providing a comprehensive summary of adverse events and other safety data, including a description of the severity, frequency, and outcome of each event. Including a thorough review of the product’s labeling and instructions for use, to ensure that they are accurate and up to date. Continuously monitoring the safety and performance of the product and updating the PSUR as needed.

RegDesk is a holistic Regulatory Information Management System that provides medical device and pharma companies with regulatory intelligence for over 120 markets worldwide. It can help you prepare and publish global applications, manage standards, run change assessments, and obtain real-time alerts on regulatory changes through a centralized platform.

What is the importance of reporting in pharmacovigilance?

Introduction – The past decade has seen the impressive growth of patient involvement in healthcare, to the point that the term ‘patient centricity’ has been introduced steadily in all patient-related activities. This is particularly true in clinical research, where patients have gone from being passive recruited subjects to active participants thanks to the realization that if something is meant to benefit the patient, then the patient must be included in the process and his/her voice must be as relevant as that of the other stakeholders in order to obtain better-quality medicines that really improve lives.

• Much effort has been put into developing new methodologies for collecting the patient perspective along the clinical trial journey, as a result of which patient-relevant outcomes nowadays are an integral part of COAs (clinical outcome assessments) side-by-side with medically relevant outcomes.
• Even more interesting is the fact that regulatory agencies like the FDA and EMA are encouraging the involvement of patients in clinical research, and the FDA has gone as far as publishing a series of guidance documents ( www.fda.gov/drugs/devoration-patients-voice-medical ) on how to involve patients in research that are shaping the way the pharmaceutical industry is re-thinking its approach to patient participation in clinical trials.

In this evolving scenario, pharmacovigilance has not been a large experimental ground for patient participation; on one hand this is because it has always been perceived as an area where only healthcare professionals have the right competence to deal with adverse events and the associated risks, and on the other hand, because patients have not been encouraged to play a more active role in this issue.

1. The most important objective of pharmacovigilance has been, until recently, the detection and reporting of serious side effects, a task well accomplished by the very accurate current pharmacovigilance systems that guarantee patient safety and quick response to any alert.
2. However, with an increasing number of drugs being approved on shorter trials that involve fewer patients, getting accurate reports of adverse events and side effects after approval is becoming a necessity.

Confirmation of this trend is not difficult to find, if we consider how much importance real world evidence has gained in regulatory evaluations, which means that reports coming from patients describing their experiences with new drugs, including minor adverse events, will likely play a bigger role in the future when regulators have to decide whether to grant approval.

Hard evidence can also be found in a recently published review of the FDA, ‘Reported use of patient experience data in 2018 drug approvals’, where patient experience data (PED) is defined as the systematic collection of meaningful data relating to the experiences, perspectives, needs, and priorities of patients.

Of the 59 approved new molecular entities in 2018, 48 include a table summarizing whether PED was or was not used during the FDA drug review. Thirty-four of those 48 approvals (70.8%) reported using PED in the drug review. Patient-reported outcomes (PROs) represented the most significant source of PED, and were used in 60.4% of approved drug reviews.2 As a result, it is reasonable to assume that direct patient reporting in pharmacovigilance could in the future become a PED that will help regulators make a decision about approval.

This is even more the case if we consider that minor adverse events are becoming more relevant to patients as they impact directly on their quality of life, while doctors often do not have the time to report them and often underestimate the burden of minor side effects for patients. Expert patients, on the other hand, understand only too well that minor adverse events play an important role in a patient’s decision to stick to the treatment plan or not.

For example, a medium-intensity itch with no serious repercussions on health might seem perfectly endurable by most, doctors included, but when it occurs almost daily it might eventually lead to the patient giving up his/her treatment plan. Therefore, minor adverse events should be taken into careful consideration, and this is an issue in which patients can play a leading role.

Moreover, chronic patients are increasingly eager to play an active part in the management of their care and to take more responsibility for their health issues, including pharmacovigilance. This is confirmed by looking at the growth in patient reporting in the Netherlands after 2003, when the Pharmacovigilance Centre LAREB implemented patient reporting to their spontaneous reporting system ( Figure 1 ).

The number of reports by patients grew rapidly, highlighting the need to evaluate the value of the patient reporting scheme and to compare experiences with other countries.3 Patient reporting in the Netherlands. (Source: LAREB).4

Is PSUR required for MDD?

I only currently hold a MDD Certificate do I need to also prepare a PSUR? ‘ YES! The requirements of this Regulation relating to post-market surveillance, market surveillance, vigilance, registration of economic operators and of devices shall apply in place of the corresponding requirements in those Directives.

What is the difference between safety reporting and pharmacovigilance?

Difference between Drug Safety and Pharmacovigilance Drug Safety & Pharmacovigilance are receiving more attention than any these days. “Drug Safety and Pharmacovigilance” is not a single term. There is a slight difference between “Drug Safety” and In short, we can say one is reactive, and the other is proactive.

The two words Drug Safety and Pharmacovigilance can be used conversely – the same primary role is being performed. But Pharmacovigilance is more encompassing and more strategic. Feel free to share this article with your colleagues. This not only shows that you have the expertise needed for the job or the project, but certifications also showcases your dedication towards what you do, giving credible proof that you have full fledged knowledge on the topic.

How often is a PSUR submitted?

Frequency of Submitting a PSUR – The frequency of submitting a PSUR depends on the regulatory classification of your medical device and the stage at which the development and marketing of the device are. For instance, for approved medical devices that have yet to be released to the market, you must submit a PSUR at least every six months after authorization until you place your medical device on the market.For devices that are already on market on the other hand, submission frequency is either at least every 2 years, or at least every 1 year, depending on the regulatory class.

1. The same is true for IVDR products.
2. A report that covers the period during which the device is launched is considered to be the last of the six-month PSURs you’re required to submit before the “preliminary placement of the product on the market.” Note that the date of your initial placement should fall after the European Birth Date (EBD).

After the initial placement of your medical devices on the market, the subsequent PSURs should be submitted after six months for the first two years, annually for the subsequent two years, and every two years thereafter. For devices on a six-month submission schedule, you can submit a request to the regulator or NB to move your submissions to annually if you want them to align with your EU signal detection submissions.

1. You should submit your PSURs immediately if the VMD requests them on an ad hoc basis.
2. Fortunately, you can agree with the regulator on the appropriate Data Lock Point (DLP) and submissions date, based on how urgently they need the report.
3. A different submission schedule may be set, especially when you’re requesting marketing authorization as a condition for approval, or because of serious safety concerns discovered during marketing.

For medical devices already on the market, the MDR requires PSUR submissions according to device risk class. Class IIa devices must submit a PSUR during Notified Body Conformity Assessment reviews. Class IIb non-implantable devices must also submit a PSUR during Notified Body Conformity Assessment reviews; however this must occur at least every 1 year.

• Class IIb implantable and Class III products must also submit a PSUR at least every year; however these PSURs can be submitted via EUDAMED, for Notified Body review.
• For IVDR products, the requirements are similar.
• Class C IVDRs must submit a PSUR at least every year during Notified Body Conformity Assessment reviews.

Class D IVDRs must also submit a PSUR at least every year; however they can be submitted via EUDAMED for Notified Body review.

What is the difference between PSUR and Psusa?

Periodic safety update reports (PSURs) – Periodic safety update reports are used by regulatory authorities to evaluate the benefit-risk balance of a medicine throughout its lifecycle. PSURs help to identify new safety concerns and allow proactive risk management to minimise the potential for harm to patients.

When should a DSUR be submitted?

The start of the annual period for the DSUR is the month and date of the DIBD. The data lock point (DLP) of the DSUR should be the last day of the one-year reporting period. The DSUR should be submitted to all concerned regulatory agencies no later than 60 calendar days after the DSUR data lock point.

Jack Gloop