The coming into effect on 1st November 2 of the new European pharmaceutical legislation has profoundly changed the approach to pharmacovigilance (PHV).
If the single market in pharmaceuticals and the maintaining of a high level of protection of public health remain the two main objectives, the new legislation benefits especially patients by giving them faster access to new medicinal products.
To prevent this from happening to the detriment of safe use for the patient, these new provisions have been accompanied by increased market surveillance and strengthening of procedures for monitoring and pharmacovigilance.
Today, pharmacovigilance is assimilated to risk management and can be described as the sum of techniques for the evaluation of the risk of occurrence of adverse effects with medicines after being marketed.
The objectives of pharmacovigilance are:
- Early detection of unknown or insufficiently documented adverse effects and interactions.
- Detection of an increase of the frequency of a known adverse effect.
- Identification of risk factors and mechanisms that are at the basis of the occurrence of adverse effects.
- Continuous reevaluation of the risk-benefit balance of medicines.
Distribution of information about adverse effects and interactions so that they occur less frequently and in order to have less therapeutic errors.
At the Federal Agency for Medicines and Health Products (FAMHP), this desire to move from passive pharmacovigilance to active pharmacovigilance, has resulted in the implementation of various projects and in programming of PHV inspections.
Planning pharmacovigilance inspections
PHV inspections began in Belgium during the second quarter of 2008 according to a schedule developed within the Vigilance and Production-Distribution departments.
This schedule includes
- Inspections to be carried out by Belgium under the inspection program designed by the European EMEA for medicinal products (human and veterinary) authorized via the centralized procedure;
- National routine inspections with a priority given to inspections of MA holders of medicinal products for human use;
- and targeted national inspections [initiated following the notification of incidents reported by the evaluators and / or by case managers of the Belgian Centre for Pharmacovigilance for Medicinal Products for Human Use (CBPH), requested by other departments following complaints or by the competent authorities of other Member States, ...]. Unlike routine inspections, targeted inspections may not be advertised to MA holder.
The choice of firms subject to routine inspections is based on risk factors identified by the Vigilance Department and areas of excellence of FAMHP.
The choice of firms subject to targeted inspections is based on a signal brought to the attention of inspectors.
Objective of pharmacovigilance inspections
The goal of PHV inspections is to ensure that MA holders have a qualified person in PHV and a pharmacovigilance system in accordance with the current legislation, and to appreciate the effectiveness of department(s) and / or system(s) involved in the tasks of pharmacovigilance.
Ranking of deficiencies in PHV
Deficiencies in pharmacovigilance are classified into three categories.
- Critical Deficiencies
Gaps in the PHV system, practices and processes that
- Cause significant effects that run counter to the rights, safety or welfare of patients, or
- Cause a serious risk to public health, or
- Indicate a serious violation of the law.
- Major Deficiencies
Gaps in the PHV system, practices and processes that
- Could cause significant effects that run counter to the rights, safety or welfare of patients, or
- Could cause significant risk to public health or
- Indicate a major divergence from the law.
- Minor deficiencies
Gaps in the PHV system, practices and processes that should not cause non-compliance of rights or harmful effect on the safety or the well-being of patients.
Given the individual nature of each inspection, critical, major or minor deficiencies will be evaluated on a case by case basis depending on the negative impact they generate (or are likely to generate) on human or animal public health.
Gaps, not considered as major in isolation, can become a major deficiency when combined.
Possible actions of FAMHP for non-compliance of the PHV system
In case of non-compliance with legal obligations concerning PHV, FAMHP currently considers various actions:
- education and recommendations to the MA holder to improve its system of pharmacovigilance, its practices or processes and introduction of an action plan;
- formal warning reminding the legal obligations of PHV;
- administrative fines;
- urgent actions (suspension or cancellation of registration of the QPPV on the list, amendments to the SPC, withdrawal, suspension of the MA, recall ....).
These actions will be taken in the order listed above, FAMHP wishing to keep the radical measures for "serious" non-compliance or for non-compliance with previous commitments.
Pharmacovigilance inspections in the European context
PHV inspectors of FAMHP maintain regular contacts with national authorities of other Member States and with the Committee for Medicinal Products for Human Use (CHMP) and the Committee for Medicinal Products for Veterinary Use (CVMP).
They are part of the PHV Inspectors Working Group, which meets four times a year and is responsible for harmonizing PHV inspection procedures in the Community and drafting the guidelines.
They participate in the EU Inspector's Training Courses.
They participate and carry out inspections of PHV at the request of the EMEA.
Person responsible for pharmacovigilance (QPPV) and local contact person
- The role and responsibilities of the person responsible for pharmacovigilance are detailed in GVP Module I.
- The requirements for the local contact person are detailed in article 66 §2 in the royal decree of 14th December 2006 concerning medicines for human use.
Administrative formalities in connection with the person responsible for pharmacovigilance
- The holder of a marketing authorisation (MA) must be assisted permanently and continuously by a qualified person responsible for pharmacovigilance who resides in the EEA (European Economic Area)
- The holder of a marketing authorisation (MA) must also be assisted by a local contact person.
Circular 600 (and annex I and annex II) gives more information regarding the obligation for the MAH to notify the local contact person and current information regarding pharmacovigilance to the FAMHP.
More explanation regarding the requirements for the local contact person and related legislation are described in a Q&A (version October 2013).