What are the PSMF regulations in extra-EU countries? And how to manage the requirements between global and local? The answer was given at the European Pharmacovigilance Congress held on 26th and 27th November 2020 of which we were sponsors.
The topic was addressed by Dr. Margherita D’Antuono Corporate PV Director, EU QPPV of Italfarmaco. Here’s what emerged.
PSMF: what is it
The PSMF is the document that describes in detail the pharmacovigilance system used by the MAH for one or more authorized medicines. It is a legal requirement that the QPPV must put in place.
However, the QPPVs must reside within the reference area, so in the case of a company with branches abroad, it is inevitable to delegate the role to the various sites. Here, more roles are put in place: the Head of Global PV EU-QPPV which oversees the Extra EU-QPPV which in turn supervises the work of the Extra EU-Local QPPV.
The delegation must be carefully detailed and described in a cascade system of delegation and supervision.
PSMF: extra-EU requirements
Eurasian Economic Union (EAEU)
In this area, the rules in force are the Rules on good pharmacovigilance practice of the Eurasian Economic Union.
The PSMF must be located within the EAEU or in the main place of the pharmacovigilance activity or in the place where the QPPV is responsible for conducting the pharmacovigilance.
In the event that the main activity is carried out outside the EAEU, or it is impossible to determine the location of the main place, the master file must be located in the place of activity of a QPPV.
The Competent Authority of a member state of the EAEU must be informed of the location of the Master File and must be informed immediately of any change in its location.
The format can be either paper or electronic and the English version is accepted together with a short description by the MAH in Russian.
In the Arab countries, the Guideline on Good Pharmacovigilance Practice for Arab Countries is followed.
The PSMF must be located in the Arab country concerned.
If the main activities take place outside, for example in case of multinational, the location must be that one where the main pharmacovigilance activities are carried out, or where the QPPV operates, such as in the headquarters for example. In this case, however, the PSMF must be made available to the National Medicines Authority in the Arab Country concerned at any time. Moreover, the local/affiliate office of the MAH must have a detailed description of the local pharmacovigilance system/activities. If the request is received from the National Medicines Authority in the Arab countries concerned, the PSMF must be provided within 14 days of receipt of the request.
The MAH will instead be asked for the PSMF and the PSSF, Pharmacovigilance sub-system file, which describes the key elements of pharmacovigilance activities in the Arab country concerned.
All System Master File files must be registered with the National Medicines Authority in the Arab country concerned.
In India, the reference document is the Pharmacovigilance Guidance Document for MAH of Pharmaceutical Products.
The PMF must be located to the MAH organization in India where the main pharmacovigilance activities are carried out.
Under the Schedule-Y of Drugs and Cosmetics Act, 1940 and Rules, 1945, the MAH must train, qualify and appoint a Pharmacovigilance Office In charge (PvOI), that is a person resident in India responsible for managing pharmacovigilance activities. Information relating to the PvOI must be included in the PvMF.
In the UK we refer to Guidance on the qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF).
From 1 January 2021 MAHs in the UK will have to:
- manage a pharmacovigilance system for products authorized in the UK
- maintain System Master File and make it electronically or physically accessible from the UK on the same site where AE’s reports can be accessed.
- have a QPPV responsible for establishing and maintaining the pharmacovigilance system for products authorized in the United Kingdom.
The QPPV can reside and operate in the EU or UK. In the event that the QPPV resides in the EU, the MAH must appoint a national contact person for pharmacovigilance who resides in the UK and reports to the QPPV. This person will have to:
- or to have access to reports of suspected adverse reactions under regulation 187 of the HMR (Human Medicines Regulations) and the PSMF for products authorized in the UK
- or to answer pharmacovigilance questions raised by the MHRA, including via inspections.
A temporary exemption has been provided for his appointment, which allows the MAHs 12 months from January 1, 2021.
All PSMFs covering UK-authorized products must be registered with the MHRA.
Application for the unique UK PSMF number has to be submitted to the MHRA; from 1 January 2021, it will also be possible to do so through the MHRA Submissions Portal.
Managing all these PSMFs is not easy as there is no global consensus between Competent Authorities or common requirements. The holder of the marketing authorization must keep the reference file of the pharmacovigilance system updated and, if necessary, revise it to take into account the experience acquired, technical and scientific progress and changes. Considering the complexity of the Pharmaceutical Company, the number of EU and non-EU affiliates, there should be a dedicated function as Global PSMF Coordinator – concludes Dr. D’Antuono.