There was two days of congress rich in topics: 11 discussion sessions, more than 150 participants and more than 30 pharmacovigilance expert speakers from competent authorities and pharmaceutical companies.

The main topics of this third edition were:

  • Updates from the main Organizations
  • Overview of inspection trends
  • Pharmacovigilance systems
  • Risk management and risk minimization
  • Patient Support Programs (PSP) and Medical Information (MI)
  • Special population and rare disease.

Let’s see them in detail.

1. Update from the international pharmacovigilance organization
The ICH is an arrangement bringing together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration. Since its inception in 1990, it has constantly evolved to respond to the increasingly global face of drug development. Its mission is to achieve greater harmonization worldwide to ensure o ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner. Harmonisation is achieved through the development of ICH Guidelines via a process of scientific consensus with regulatory and industry experts working side-by-side. Key to the success of this process is the commitment of the ICH regulators to implement the final Guidelines.

2. Pharmacovigilance inspections: current and future landscape The ultimate purpose of the inspection is to ensure that the MAH has a pharmacovigilance system that complies with the regulations, has a qualified person (QPPV) and that the various departments work effectively. On the basis of the size of the pharmaceutical companies, the difficulties change: for small companies the biggest difficulty is to incorporate specific skills for each pharmacovigilance obligation, while for large companies the problems are related to internal communication. However, the inspector focuses on specific areas depending on the type of reality and the asset of the outsourced activities.

3. Updates on EudraVigilance and EVDAS
Starting from 22 November 2017, the new EudraVigilance system (EV) and the EVDAS data analysis system were put online. Exactly 3 months later a pilot phase was launched for MAHs of products containing active substances under additional monitoring, which must use EVDAS for signal search. This pilot phase, which was to end a year later, has been extended. However, the introduction of these new work tools has led to a different difficulty:

  • increase in work
  • creation of duplicates set up by multiple submission of cases to the competent authorities
  • lack of confidence in the exclusive ICH E2B (R3) download process due to the complexity, to the point that several MAHs still operate an ICH E2B (R2) security database
  • lack of harmonization between the European Economic Area and non-EU countries, which leads to a duplication of relations outside the EEC, with the real risk of generating false safety signals
  • difficulty in managing the day 0 since no official definition has been provided. The non-EEC regulators are not familiar with the ICSR download specifications and therefore they don’t’ give instructions to the MAHs in CEE for the day 0 in the respective territories or for the obligation, or not, to report the ICSR downloads from EV
  • difficulty in identifying false safety signals resulting from duplicate ICSRs submitted to EV. These duplicates must be communicated to the EMA via the service desk by the marketing authorization holders, contributing to the improvement of the contents of the EV database.
    Furthermore, due to the relocation of its headquarters in Amsterdam, the EMA has delayed some of the initially established deadlines.

4. Signal management
In order to comply with the requirements of signal detection and management, the MAHs must:

  • monitor the safety of their medicines
  • monitor the data reported in EudraVigilance
  • a carry out signal detection through multiple sources
  • collaborate with the PRAC providing the additional information requested
  • keep their product information up-to-date.

To improve and make all these processes more efficient it is good to use an automated database implemented by signal detection and signal management applications. It is possible to carry out the signal detection even without automations, but in this case the MAH will have to apply not a few precautions such as:

  • implement quantitative metrics such as “Reporting Rate” that can help identify changes in frequency of reporting of a drug-event combination (DEC), which can generate a signal
  • use the eRMR downloaded from the EVDAS in a more extensive way, looking for and analyzing also the DEC not marked as DSP
  • establish rules to define when a quantitative measure of a DEC should represent a signal
  • improve the qualitative review of ICSRs and set rules to define when a DEC observed with qualitative methods should represent a signal and trigger actions to validate or deny it
  • implement “designated medical events” and “product-specific targeted medical events” lists.
  • implement a robust tracking system for signal management that allows adequate audit trails and satisfies the pharmacovigilance inspectors.

5. Involvement of patient experts: central role in pharmacovigilance for better and safer use of medicinal products
The work that the PRAC is carrying out in order to make the patient more aware of the importance of reporting adverse events is increasing. In fact, it was found that in 2018 reports from European patients and consumers increased by 91%, a success factor considering the great importance that these reports have: patients, in fact, being the interested parties can provide relevant details that the doctors instead tend to exclude giving it little importance.
The information could come from organized systems, such as surveys by the PRAC, or from digital sources, such as websites or social media. In this case some verifiable problems are the identifiability of the user (fake profiles), the impossibility of carrying out follow-up activities, untrustworthiness of the information.

6. Pharmacovigilance in the special population: geriatrics, pediatrics, pregnancy and breastfeeding
In Special Populations, drug reactions can be very different compared to the average population. Whether it’s the elderly, children or pregnant women, the data from clinical studies are very limited. These in fact tend to be excluded from the tests thus leading to a gap in important information. Instead, it would be good to include them from the earliest stages of studies or intensify the post-marketing pharmacovigilance in order to better understand the risks and benefits of a specific drug.

7. Pharmacovigilance in the framework of advanced therapies and rare diseases
For advanced therapies and rare diseases the available data are very limited, in fact the population sample very often does not reach the hundred, or slightly exceeds it.
To take advantage of the few data available, it is good to use all possible sources, from preclinical and clinical data to epidemiological data, from those from relevant class drugs to those from patient support groups.
In the future, “big data” monitoring tools will facilitate the availability of information and the risk/benefit ratio will be easier to optimize.

8. Risk management and risk minimization
The ultimate aim of the risk management plan is to optimize the benefit/risk profile of a medicine through a risk management system, which identifies, characterizes and minimizes risks.
Risk minimization activities are divided into:

  • Routine Risk Management, which uses prescribing information to doctors, such as a summary of product characteristics and to patients, as an information leaflet for patients, to inform and guide the best way to avoid or reduce known risks.
    Effectiveness is usually measured through regular signal detection methods and reviews in periodic safety reports.
  • Additional Risk Management, which includes activities beyond those mentioned above and deemed necessary in the EU, usually involve specific professional education for health personnel and patient education, which also includes letters from Dear Healthcare Professional approved by regulatory agencies.

The GVP XVI module divides the measurement of effectiveness into two categories: process indicators and exit indicators. The process indicators include the measurement of the effectiveness of the distribution of materials and the proof of the understanding of the materials by the recipients. The distribution of materials can be documented by careful maintenance of material receipt records. Understanding materials is often demonstrated using market research methodologies such as surveys on prescribers and patients. Data on result indicators that require a demonstration of risk reduction may be more difficult to obtain.

9. Patient Support Programs and Medical Information
The pharmacovigilance team is responsible for acquiring and analyzing information on drug safety and sharing it with healthcare professionals, patients and all stakeholders. A valid help could come from the Medical Information team or better from its collaboration with the pharmacovigilance team: since the MI team is in contact with patients, it should be trained to extrapolate as much information as possible during an episode of adverse reaction and report then to the pharmacovigilance team. The latter, instead, could learn in practice the use of a product.
The medical information team is also “eyes”, “ears” and “voice” of the company, as it is often involved in meetings of the brand team, approval of promotional items, advisory committees, preparation of specific websites for companies and diseases and other business activities of which PV cannot be part.

10. Pharmacovigilance systems: organization and quality
The speakers of this session addressed several issues.
The importance of data integrity and the relative difficulties. The variety of sources and the increase in data to be evaluated does not make it easy to collect and maintain information integrity. More and more companies, in order to maintain a high level of effectiveness, decide to go to third parties or to invest in a more effective management system for the management of pharmacovigilance.
The relief of the figure of the EU QPPV. This role has become increasingly important in recent years, thanks also to its role as a bridge between Europe and foreign countries. He is the person who, thanks to his skills, can coordinate and monitor all the pharmacovigilance activities necessary even in non-EU territories. In fact, its requirements require knowledge of the pharmacovigilance regulations of other countries, ability to negotiate agreements, prepare and maintain adequate documentation, and supervise the pharmacovigilance system. Currently, his figure can help the Brexit management.
Quality in relations with suppliers. In order to guarantee the quality, during the relationship with the suppliers the procurement process, the determination of the service execution methods and the governance structure to supervise the work must be carefully coordinated and stipulated. Furthermore, the delimitation of operational responsibilities between sponsor/producer and vendor/service provider must be documented and be clear to all parties, so that quality supervision can be adequately demonstrated.

11. Pharmacovigilance in clinical trials
In this session too there are several topics addressed.
Early Access Program (EAP). These programs allow pre-approval access to medicines for patients who have exhausted all alternative treatment options and do not meet the criteria for access to clinical trials. They require detailed plans and implementation times that involve a dedicated multi-functional team and the collection and reporting of adverse events are mandatory: the attending physician must report to the regulatory authorities any serious and unexpected AE / ADRs and must report to the company, or the producer of the drug, any SAE that occurred during treatment.
Furthermore, it is good to have a clear communication strategy relating to the position of the EAP company, eg. Website,, publication of the company policy.
Pragmatic approaches for PV in clinical trials. The new regulation 536/2014 “The Clinical Trials Regulation” will come into force, which will make changes such as: simplified application procedure through a single access point, single authorization procedure for all clinical studies, authorization by Member State, involvement of ethics committees in the evaluation procedure, simplifies the communication on safety by SUSAR sponsors who are sent directly to the EudraVigilance clinical trial module (EVCTM).
Challenges of RSI Management: a non-commercial sponsor perspective. The RSI is a key document for conducting pharmacovigilance in clinical trials, as is the related question and answer document which adds clarity to certain aspects such as content, timing for updating, approval and implementation. However, this document was drawn up mainly for commercial sponsors, while for non-commercials it remains unclear. Documentation and alignment of sponsor processes with European legislation is necessary in order to achieve a study result in accordance with the regulations.