What does Pharmacovigilance entail?
Last updated on: Sepetember, 2024
The notion of Pharmacovigilance, originating from the Greek and Latin roots 'Pharmakon' (referring to medicinal substance) and Vigilia (meaning to keep watch), surfaced around two centuries ago among medical professionals and experts. Initially, it primarily involved physicians documenting the safety and efficacy of different drugs administered to patients.
Presently, the World Health Organization (WHO) characterizes Pharmacovigilance as “The science and activities concerned with detecting, assessing, understanding, and preventing adverse effects or any other drug-related issues.”
WHO outlines three crucial prerequisites for the approval of any newly developed drug by Regulatory agencies: quality, effectiveness, and safety for intended purposes.
The realm of Pharmacovigilance has significantly expanded in recent years. WHO now encompasses areas such as:
- Drug interactions
- Misuse and abuse of drugs
- Counterfeit drugs
- Medication errors
- Adverse drug reactions/incidents
- Lack of drug efficacy
Pharmacovigilance extends beyond drugs to include:
- Vaccines
- Blood products
- Medical devices
- Biologicals
- Herbals
- Traditional/Complementary substances
The rise of consumer advocacy and increased focus on public health, along with heightened Regulatory scrutiny, emphasizes the importance of consistent Pharmacovigilance strategies.
High-quality Pharmacovigilance is crucial not only for successful premarket evaluation of pharmaceuticals but also for post-market surveillance.
Given the expanded scope, complexity, and responsibility, these practices are now commonly known as Good Pharmacovigilance Practices (GVP).
What is the objective of Pharmacovigilance ?
Pharmacovigilance aims to:
- Enhance patient care and safety regarding medication and medical interventions
- Enhance public health and safety regarding medication use
- Identify medication-related issues and promptly communicate findings
- Assist in evaluating the balance between benefits and risks of medications, thereby preventing harm and maximizing benefits
- Encourage safe, rational, and effective (including cost-effective) medication use
- Foster understanding, education, and training in Pharmacovigilance, and effectively communicate its importance to the public
How does a Pharmacovigilance inspection work?
To ensure compliance with drug safety monitoring requirements, Marketing Authorization Holders (MAHs) must undergo audits of their Pharmacovigilance systems (PV systems) by both internal and external auditors, as well as inspectors from national competent authorities.
The reality is that MAHs who have not yet been inspected will inevitably face this challenge, while those who have already undergone inspections should be prepared for potential re-inspections.
Inspections carried out by different competent authorities may vary in their procedures, but one thing remains consistent: if a Pharmacovigilance system is functioning effectively, there should be no cause for concern. However, if deficiencies are identified, expert inspectors will readily spot them, potentially leading to significant consequences for the MAH.
Various types of Pharmacovigilance inspections exist, with the process influenced by multiple factors. Inspections may be either announced, typically as part of a planned inspection schedule known as 'routine' inspections, or unannounced, often triggered by specific issues ('for cause' inspections). They can focus on specific aspects of the Pharmacovigilance system or encompass the entire system. Additionally, pre-authorization PV inspections (for Marketing Authorization Applicants) may be requested under specific circumstances.
A Pharmacovigilance inspection can last from a few days to a week, depending on the size and complexity of your company's system and products. Inspectors will review your Pharmacovigilance system, documents, and databases. They'll also interview key personnel, including the Qualified Person Responsible for Pharmacovigilance (QPPV). Be prepared to answer detailed questions about your system and demonstrate its effectiveness.
What are common discoveries and consequences during PV inspections?
Even if the MAH delegates its PV tasks to another Pharmacovigilance service provider, the MAH retains all responsibilities for Pharmacovigilance. Therefore, it's crucial to maintain oversight of all activities conducted.
To grasp the extent of these duties, let's examine some common inspection findings:
- Adverse Reactions (ARs): Delayed or incorrect submission of reports; underreporting or inaccuracies in reporting; inadequate evaluation of adverse reaction reports; lack of or delayed follow-up on reports.
- Quality Management Systems (QMS): Outdated, incomplete, or missing standard operating procedures; deviations not managed according to established procedures.
- Pharmacovigilance System Master File (PSMF): Documentation not reflective of the actual PV system; incomplete or outdated annexes.
- Organization and staff: Qualified Person for Pharmacovigilance (QPPV) inadequately qualified or lacking oversight; insufficiently trained staff for compliance.
- Literature searching: Non-compliance with legislative requirements; inadequate local literature reviews.
- Periodic Safety Update Reports (PSUR): Late submission or content not compliant with regulations.
- Reference Documentation: Safety variations not submitted within deadlines; lack of submission procedures.
- Cooperation agreements: Missing documents; contracts lacking information on adverse reaction data exchange; lack of reconciliation of information.
- Audits: Partner audits not conducted within the Pharmacovigilance context.
- Electronic databases: Lack of change tracking for critical processes; unvalidated systems; discrepancies between source data and database entries; deficiencies in data quality control or access control.
When non-compliance with Pharmacovigilance responsibilities is detected, the Regulatory authority will assess the situation case by case. The actions taken will depend on the potential impact on public health. Possible Regulatory actions include sharing findings with other competent authorities, re-inspection, issuing warning letters or infringement notices, listing MAHs as extremely or persistently non-compliant, suspension or revocation of marketing authorization, product recall, imposing financial penalties, or referring for criminal prosecution, possibly resulting in imprisonment.
Good Pharmacovigilance Practice (GVP)
Good Pharmacovigilance Practice (GVP) entails a set of principles and procedures designed to safeguard the safety of medical products, particularly drugs and vaccines. Its objective is to mitigate risks associated with these products by fostering their safe usage and by identifying, evaluating, and averting adverse effects or other safety concerns.
Regulatory bodies like the European Medicines Agency (EMA) and the United States Food and Drug Administration (USFDA) issue GVP guidelines, providing a framework for pharmaceutical companies, Regulatory authorities, and healthcare practitioners. These guidelines encompass various aspects, including:
- Risk management: Mandating Pharmaceutical companies to develop risk management plans that identify, evaluate, and address the risks linked with specific medical products.
- Safety monitoring: Requiring companies to establish systems for monitoring product safety, including the collection and analysis of adverse event reports.
- Signal detection: Ensuring companies set up and maintain systems to detect safety signals and investigate them thoroughly.
- Pharmacovigilance inspections: Conduct routine inspections by Regulatory authorities to verify compliance with GVP guidelines.
- Safety reporting: Compelling pharmaceutical companies to promptly report safety data to Regulatory bodies, including serious adverse events and potential safety signals.
Adhering to GVP guidelines enables pharmaceutical companies to fulfill their Regulatory responsibilities in monitoring and reporting product safety, while Regulatory authorities can ascertain the safety and efficacy of medical products for patients. Ultimately, GVP aims to enhance patient safety and mitigate risks associated with medical product usage.
Global and Regional Regulatory requirements
Global and Regional Regulatory requirements dictate that pharmaceutical companies must report safety information from clinical trials and marketed products to Regulatory authorities, a mandate that has been in place for many years. However, each national authority has distinct requirements, leading to diversity in reporting standards. Efforts have been made to harmonize reporting standards under the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), which brings together Regulatory authorities and experts from Europe, the USA, and Japan. Despite these efforts and the existence of European Directives and Regulations, there remains variation in requirements, and guidance from the CPMP Pharmacovigilance Working Party is still forthcoming.
In the UK, requirements for investigational drugs are outlined in the CTX/CTC guidance, while those for licensed products are detailed in the MCA publication Medicines Act Information Letter No 87. For marketed products, individual serious suspected reactions (expedited reports) must be submitted to the MCA within 15 calendar days of receipt by the company. Similar requirements exist in other EU countries but may differ in detail. Companies developing or marketing products in the USA must adhere to extensive FDA reporting regulations with strict deadlines.
A notable aspect of European requirements is that Marketing Authorisation holders, i.e., companies, must appoint a suitably qualified person responsible for Pharmacovigilance. Their duties include establishing and maintaining a system to collect and collate all Adverse Drug Reactions (ADRs) reported to company personnel, preparing various reports, and responding to requests for additional information from authorities. Meeting global Regulatory reporting requirements is a significant business imperative in Pharmacovigilance, necessitating substantial investments in staff, computer systems, and procedures. However, emphasis on compliance should not overshadow the importance of sound scientific judgment in identifying and analyzing critical safety issues with products.
Pharmacovigilance extends beyond reporting cases to Regulatory authorities; Post-Marketing Surveillance (PMS) and hypothesis testing yield valuable information that can be communicated to prescribers through updates to Summary of Product Characteristics (SPC)/data sheets and Patient Information Leaflets as safety signals are confirmed. While many updates are initiated by companies, some are mandated by authorities. The CIOMS III Working Group has compiled valuable commentary and guidance on essential safety information that should be available for a product.
Knowledge, attitude, and practice of Pharmacovigilance in developing countries
In developing countries, Pharmacovigilance faces various challenges but is gaining recognition as a crucial component of public health. Awareness about Pharmacovigilance is often limited among healthcare professionals, regulators, and the general population due to inadequate training and resources. Many healthcare systems lack robust Pharmacovigilance infrastructure, including proper reporting mechanisms and databases. There is increasing acknowledgment of the significance of Pharmacovigilance, yet the willingness to report Adverse Drug Reactions (ADRs) can be affected by factors like fear of legal repercussions, limited understanding of the reporting procedures, and doubts about the effectiveness of reporting. Despite challenges, efforts are being made to improve Pharmacovigilance practices in developing countries. This includes strengthening Regulatory frameworks, enhancing healthcare professionals' education and training on Pharmacovigilance, promoting ADR reporting culture, and fostering collaboration with international Pharmacovigilance networks. However, there's still a need for sustained investment and commitment to overcome barriers to effective Pharmacovigilance implementation.
Regulatory Process in the United States of America, Europe, China, and Japan
Pharmacovigilance Regulatory processes vary across different regions such as the United States, Europe, China, and Japan. Each jurisdiction has its own set of regulations and agencies responsible for overseeing drug safety. Below is a short explanation of the PV Regulatory processes in each of these regions:
- United States of America (U.S.A.):
- Regulatory agency: The Food and Drug Administration (USFDA) is responsible for regulating drugs in the United States.
- Pharmacovigilance regulation: In the U.S., Pharmacovigilance is governed by the FDA's Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER).
- Reporting: In the U.S., Pharmaceutical companies, healthcare professionals, and consumers can report adverse events through the FDA's Adverse Event Reporting System (FAERS). These reports are used to monitor drug safety and inform Regulatory decisions.
- Regulatory actions: The USFDA has the authority to issue warnings, recalls, label changes, and even withdraw drugs from the market if safety concerns arise.
- Europe:
- Regulatory agency: The European Medicines Agency (EMA) oversees drug regulation in the European Union (EU).
- Pharmacovigilance regulation: Pharmacovigilance activities in Europe are regulated under the European Union Pharmacovigilance System, which includes the EMA and national competent authorities (NCAs) of EU member states.
- Reporting: Adverse Drug Reactions (ADRs) are reported to national authorities in EU member states, which then forward the reports to EudraVigilance, the centralized European database for Pharmacovigilance.
- Regulatory actions: The EMA can recommend changes to product labeling, restrictions on use, or even suspension or withdrawal of a drug if safety concerns are identified.
- China:
- Regulatory agency: The China National Medical Products Administration (NMPA) regulates drugs in China.
- Pharmacovigilance regulation: Pharmacovigilance in China is overseen by the NMPA's Center for Adverse Drug Reaction Monitoring.
- Reporting: ADRs are reported to the National Adverse Drug Reaction Monitoring Center (ADRMC) and regional monitoring centers.
- Regulatory actions: The NMPA can take Regulatory actions such as issuing warnings, restrictions, or even withdrawing drugs from the market based on safety concerns.
- Japan:
- Regulatory agency: The Pharmaceuticals and Medical Devices Agency (PMDA) is responsible for drug regulation in Japan.
- Pharmacovigilance regulation: Pharmacovigilance activities in Japan are governed by the PMDA and the Ministry of Health, Labour and Welfare (MHLW).
- Reporting: ADRs are reported to the PMDA through the Japanese Adverse Drug Event Report (JADER) database.
- Regulatory actions: The PMDA can take Regulatory actions similar to those in the U.S. and Europe, including label changes, restrictions, or withdrawal of drugs if safety issues arise.
Overall, while the basic principles of Pharmacovigilance are similar across regions, the specific Regulatory processes and agencies involved may vary, reflecting differences in legal frameworks, reporting systems, and cultural considerations.
Issue and crisis management
The processes of signal generation and hypothesis testing in Pharmacovigilance are typically long-term and continuous throughout a product's lifecycle, gradually accumulating knowledge of its safety properties. However, in certain circumstances, these processes must be accelerated due to crisis. This may arise when a safety signal suggests a new and significant risk, or due to actions by Regulatory authorities and/or mass media activities.
The hallmark of a crisis is a lack of time. Urgent actions are necessitated by potential serious hazards to patients, impending Regulatory actions, or pressures from the mass media. Simultaneously, comprehensive analysis of available data, consultations with various experts, internal discussions within the company, information dissemination to stakeholders, and other activities are required. Task forces, often comprising Pharmacovigilance experts, are typically assembled to address such crises. These task forces analyze all available data, consult with experts, manage internal and external communications, and ultimately make informed benefit-risk assessments and propose necessary actions. This work represents the true test of expertise in Pharmacovigilance-operating under extreme internal and external pressures within tight timelines.
Post-Marketing Pharmacovigilance
With a focus on ensuring the safety and efficacy of your marketed products, we offer a range of solutions tailored to meet Regulatory standards and support your ongoing pharmacovigilance needs.
For drugs and vaccines with marketing authorization, our dedicated team is committed to monitoring the risk-benefit profile of these products. We provide timely and efficient case processing, expedited reporting, and preparation of periodic safety reports such as PBRERs/PSURs and PADERs. Our global literature screening ensures that you stay informed about the latest safety data and emerging signals, while our risk management activities help mitigate potential risks to patients.
Our post-marketing Pharmacovigilance services include:
- Pharmacovigilance physician services: Expert physicians oversee the monitoring and evaluation of adverse events associated with your products.
- Preparation and submission of Regulatory reports: We assist in the preparation and submission of PBRERs/PSURs and PADERs to Regulatory authorities worldwide.
- Global literature search and review: Our team conducts comprehensive literature searches to identify relevant safety information for your products.
- EU Qualified Person for Pharmacovigilance (QPPV) and Deputy: We provide QPPV services and support to ensure compliance with European pharmacovigilance regulations.
- Pharmacovigilance awareness training and Safety Data Exchange Agreements (SDEAs): We offer training programs and assist in the negotiation and reconciliation of SDEAs with partners.
- Pharmacovigilance System Master File (PSMF) Preparation and Maintenance: We help prepare and maintain PSMFs to ensure compliance with Regulatory requirements.
- Regulatory intelligence: Our team monitors Regulatory updates and provides insights into general Pharmacovigilance requirements and product-specific information.
Pharmacovigilance Staffing
At Freyr, we understand the paramount importance of patient safety in the pharmaceutical industry. In an ever-evolving landscape of Pharmacovigilance (PV) regulations and technologies, staying ahead is crucial. That's why we are committed to providing proactive and innovative solutions that prioritize quality and innovation.
Our Approach
We believe in taking a proactive approach to Pharmacovigilance, ensuring that patient safety remains at the forefront of drug development. With our comprehensive solutions, we help you navigate the complexities of PV regulations and technologies, allowing you to focus on what matters most delivering safe and effective treatments to patients.
Global Pharmacovigilance Solutions
Whether you require a full global Pharmacovigilance solution or discrete PV functions to complement your existing infrastructure, Freyr offers end-to-end capabilities tailored to your needs. Our Functional Service Partnership (FSP) Pharmacovigilance solutions are designed to generate evidence that demonstrates the effectiveness, safety, and value of your products.
Why Choose Freyr?
![about-us]()
Expertise
Our team of experienced professionals brings a wealth of knowledge and expertise to every project, ensuring that you receive top-quality service and support.![about-us]()
Innovation
We are committed to staying at the forefront of PV regulations and technologies, providing innovative solutions to help you adapt and thrive in a rapidly changing environment.![about-us]()
Flexibility
Whether you require a comprehensive Pharmacovigilance solution or individual PV functions, we offer flexible options to meet your unique needs and requirements.![about-us]()
Quality
Quality is our top priority. We adhere to strict standards and regulations to ensure the safety and effectiveness of your products, giving you peace of mind that patient safety is always protected.
Regulatory Compliance, Drug Safety, and Pharmacovigilance
In today's rapidly evolving pharmaceutical landscape, maintaining high standards of compliance is crucial. Our team of industry experts is here to guide you through the complexities and challenges, ensuring that your business remains protected and efficient.
Our Approach:
At Freyr, we understand the importance of staying ahead in Regulatory compliance and drug safety. Our comprehensive suite of services is designed to address the unique needs of pharmaceutical companies of all sizes, from startups to established corporations. Whether you need assistance with post-approval submissions, Regulatory advice, or strategic compliance consulting, we have the expertise and resources to support you.
Services We Offer
- Post-approval submissions and lifecycle maintenance: We provide support for labeling updates and variations, allowing your internal teams to focus on strategic activities while ensuring compliance.
- Regulatory advice: Our tailored Regulatory strategies help you optimize the utilization of your approved marketing application, enabling you to penetrate multiple markets and enhance ROI.
- Strategic compliance consulting: From crisis management to proactive compliance strategies, we help you navigate every aspect of risk mitigation and compliance management.
- Auditing: Identify and resolve compliance challenges with our detail-oriented auditing services, ensuring Regulatory compliance and mitigating risks.
- Good practice advisory: Our team offers guidance on Good Distribution Practice (GDP), Good Manufacturing Practice (GMP), Good Clinical Practice (GCP), Quality Management Systems (QMS), and effective management control.
- Data integrity: Ensure data integrity and build confidence in the quality of your data through comprehensive audits and expert analysis.
- Inspection support: Minimize compliance-related rejections and ensure a smooth Regulatory inspection process with our range of services.
- Technical writing: We deliver accurate and comprehensive documentation, aligned with industry standards and Regulatory requirements.
- Consent decrees and warning letters: Navigate Regulatory challenges effectively with our strategic and operational compliance support.
- Pharmacovigilance and safety: Develop compliant strategies for risk evaluation and mitigation, prepare safety update reports, and design end-to-end safety services to support global Pharmacovigilance systems and programs.
Why Freyr
Partner with Freyr to elevate your compliance and safety standards. Our team of experts is committed to helping you navigate the complexities of Regulatory compliance and Pharmacovigilance, ensuring that your business remains compliant, efficient, and successful. Contact us today to learn more about our services and how we can support your business needs.
Competencies as a global expert in PV services?
Freyr: Global expert in PV services
Introducing Freyr, a premier provider of comprehensive end-to-end Pharmacovigilance services. With a steadfast commitment to drug safety, Freyr offers unparalleled expertise and support to pharmaceutical companies worldwide. Our dedicated team of Pharmacovigilance specialists ensures Regulatory compliance and mitigates risks throughout the product lifecycle.
At Freyr, we provide a suite of services tailored to meet the evolving needs of our clients. From adverse event reporting, literature monitoring, and signal detection to risk management and periodic safety update reports, we deliver robust solutions designed to safeguard patient welfare and uphold Regulatory standards. Our advanced technology platform streamlines data management and facilitates real-time monitoring, empowering clients with actionable insights and prompt decision-making.
What sets Freyr apart is our unwavering dedication to excellence and innovation. We continuously invest in talent development and cutting-edge technologies to stay ahead of emerging trends and Regulatory requirements. Our collaborative approach fosters strong partnerships with clients, ensuring transparency, trust, and superior outcomes.
Choose Freyr for end-to-end Pharmacovigilance solutions that prioritize safety, compliance, and peace of mind. Experience the difference with our proactive and reliable approach to drug safety management. Your patients deserve the best, and Freyr delivers.
USPs in right first-time compliance
Freyr is a pioneering Pharmacovigilance company dedicated to ensuring right first-time Compliance. With a laser-focused commitment to precision and excellence, Freyr specializes in delivering comprehensive Pharmacovigilance solutions that prioritize Regulatory adherence from the outset.
At Freyr, we understand the critical importance of getting it right the first time. Our team of seasoned experts navigate the intricate landscape of drug safety regulations, offering tailored strategies and proactive measures to ensure seamless compliance at every stage of the product lifecycle.
What sets Freyr apart is our relentless pursuit of perfection and our steadfast dedication to exceeding client expectations. By integrating cutting-edge technology, rigorous quality control processes, and continuous training initiatives, we empower our clients to achieve unparalleled levels of compliance efficiency and Regulatory confidence.
Choose Freyr for Pharmacovigilance solutions that guarantee right first-time Compliance, setting the standard for excellence in drug safety management. With Freyr by your side, rest assured that your Regulatory obligations are not just met, but exceeded with precision and proficiency.
PV Regulatory Intelligence expertise
The Life Sciences industry is governed by regulations, which are continuously evolving to help the industry players deliver the best. However, keeping up with the changes in the Regulatory intelligence in the Pharmacovigilance landscape can be challenging. To help pharmaceutical organizations in the same, Freyr provides Pharmacovigilance consulting services.
Comprehensive approach to Regulatory intelligence in Pharmacovigilance
Freyr’s approach to Pharmacovigilance consulting services is as follows:
- Primary research that covers data across country updates, Regulatory updates, congress coverage, trade association coverage, authority & ministry coverage, key opinion leaders, and influencers.
- Secondary research containing data about country/product, Regulatory landscape, clinical updates, PV intelligence, news, and newsletters.
Freyr offers comprehensive Pharmacovigilance consulting services that can help every life sciences organization create internal Regulatory intelligence Pharmacovigilance processes, thereby complying with the HA policies and laws.
Freyr provides Pharmacovigilance consulting services and offers a cloud-based Regulatory intelligence software for a complete spectrum of information that spans various industries, products, and regulation categories.
Proven expertise:
- Cloud-based Pharmacovigilance Regulatory intelligence software that provides comprehensive, global intelligence
- Pharmacovigilance consulting services on regulations for individual countries
- Region-wise product-specific (drugs, device, or biologics) guidance and Pharmacovigilance consultancy
- Country-specific regional ICSR and aggregate reporting timelines and requirements
- Local representation (QPPV, NPPV, etc.) and post-marketing authorization information
