EU rules for assignment of Local Contact Person for PharmacoVigilance (LCPPV) and Local Literature Search (LLS) are a constant source of confusion. The Industry are attempting to implement these often unclear requirements to the best of their ability.
In the following I will attempt to interpret the regulations, guidances, questions and answers and inspection experiences to the best of my ability. I cant guarantee this is a correct interpretation so double check. I welcome any comments, corrections or suggestions.
There are separate requirements for LLS and for LCPPV assignment and they are described in separate parts of the regulatory framework so I will discuss the two subjects in separate sections.
Local Literature Search (LLS) requirements
Before discussing the local search requirements it is important to keep in mind that the pharmaceutical industry and the EMA is conducting very comprehensive searches in internationally indexed literature which include more than 30 million articles and more than 6000 scientific journals from all over the world. These international indexed searches include the vast majority of relevant literature and serves as basis for identification of potential new adverse events as well as potentially important new information about the product group, The result of these searches are used in day to day safety surveillance and they are analyzed and included in aggregate reports like PBRER and/or DSUR reports – usually annually.
Global searches need to be done weekly when the product is on the market.
In addition there are local requirements for reporting of adverse events by healthcare professionals especially in the first years on the market where reporting is often mandated in the individual member-states.
The requirement for LLS is yet another requirement to do searches in local literature and local language in the individual member-states. The likelihood of ever finding anything relevant that might have been missed in the international searches and in the local adverse event reporting is extremely low, but it is included in the regulations and must be followed.
The Q&A document from December 2016 https://www.ema.europa.eu/en/documents/other/monitoring-medical-literature-entry-relevant-information-eudravigilance-database-european-medicines_en-0.pdf clarifies the requirements for LLS and states that, even products that are covered by the EMA MLM service, the marketing authorisation holder must perform the LLS in the member states. Note that the search can be done centrally as long as it covers relevant local literature from the member states.
The specific requirement is stated in GVP module VI section VI.B.1.1.2:
“In addition, marketing authorisation holders should have procedures in place to monitor scientific and medical publications in local journals in countries where medicinal products have a marketing authorisation, and to bring them to the attention of the company safety department as appropriate”,
It is not defined explicitly when this literature surveillance has to start, but the GVP module states that the requirement for LLS is for marketing authorisation holders, so consequently the requirement would not apply until a market autorisation is granted. It seems reasonable to restrict the searches to countries where the product is actually supplied as if there otherwise is no product in the local market then no-one has anything to write about. Keep in mind that any kind of market supply will count as presence on the market – for instance compassionate use supply
Local Literature Search
The requirement for local literature search in EU member states starts at the time a market authorisation is granted and applies to member states where the product is supplied to the market including compassionate use and post study expansion (un-authorised summary of the requirements)
Local Contact Person for PharmacoVigilance (LCPPV)
The rules for the assignment of an LCPPV in the individual member-states are very diverse. The general principle is that countries that have limited English speaking capabilities require the assignment of a local language speaking LCPPV, but the details vary.
In the table below you can see a summary of the requirements as they are interpreted based on the referenced laws, guidances, Q&As, agency communications and the EMA document 23-OCT-2020 “Information on the Member States requirement for the nomination of a pharmacovigilance (PhV) contact person at national level”
The table shows when the LCPPV requirement appears to be required during the marketing authorisation application process separated in time of the MA application, at MA approval date and at the time product is actually available on the market in the EU
LCPPV requirements table
| MA application | MA approval | On market | Comment | |
| Austria | – | – | – | LCPPV is not required in Austria Only if specifically required an LCPPV needs to be assigned. Austrian law § 75i (6) AMG states: “Irrespective of paragraph 5, the Federal Office for Safety in Health Care may request the appointment of a contact person for pharmacovigilance issues in Austria who will report to the pharmacovigilance officer.” |
| Belgium | X | LCPPV is required in Belgium (application) The requirement is for marketing autorisation applicants according to Circular 600. The information is based on Circular 600, annex I (LCPPV form), annex II (contact details). Contact email for FAMHP: phvinsp@fagg-afmps.be | ||
| Bulgaria | X | LCPPV is required in Bulgaria. (approval) The requirement is for marketing authorisation holders. It applies at the time of approval according to law for medicinal products in human medicine, Article 191 | ||
| Croatia | X | LCPPV is required in Croatia. (approval) The requirement is for marketing authorisation holders so it applies at the time of approval according to the legislation: Ordinance on Pharmacovigilance (Official Gazette 83/13) and Medicinal Product Act (official gazette no. 76/13) Article 3 Point 58 Information on the approval procedure of local qualified person / deputy responsible for pharmacovigilance. email: lqppv@halmed.hr | ||
| Cyprus | X | LCPPV is required in Cyprus. (application) The requirement is for marketing authorisation applicants so it applies at the time of application submission according to the legislation: The Drugs for Human Use (Quality Control, Supply and Prices) Law of 2001 (70 (I) / 2001) | ||
| Czech Republic | X | LCPPV is required in the Czech Republic (approval) The requirement is for marketing authorisation holders so it applies at the time of approval according to the legislation: The local agency SUKL has a detailled instruction here It is practical to use the same LCPPV for both the Czech Republic and Slovakia | ||
| Denmark | – | – | – | LCPPV is not required in Denmark Only required if specifically mandated. This has so far not happened. There is more details on the agency site: Pharmacovigilance legislation – questions and answers |
| Estonia | – | – | – | LCPPV is not required in Estonia But according to regulation of the Minister of Social Affairs no. 26 (§ 4section 4) Estonian speaking contact person is required for the cases where the prescribers of the medicinal products are to be informed about the safety risks associated with the use of medicines (that means both direct healthcare professional communication and materials associated with additional risk minimisation measures) As this does not seem to be a specific LCPPV but more of a general contact person this could for instance likely be in the commercial organization when the product is on the Estonian market |
| Finland | – | – | – | LCPPV is not required in Finland Only required if specifically mandated. The Finnish Medicines Agency (Fimea) may request the nomination of a pharmacovigilance (PhV) contact person at national level. There is more details in the medicines legislation 30 c § (3.5.2013/330) |
| France | X | LCPPV (physician or pharmacist) is required in France for any company that promotes and distributes human medicinal product(s) (MAH or not) (market) ANSM provides an extensive Q&A document online related to the requirements. In this document it is clarified that a LCPPV must be in place when the company use or promote a product in France: “The appointment of an RPV must be made as soon as a company uses a medicine, in accordance with the provisions of Article R. 5121-164 of the Public Health Code (CSP): “any company or organization using a medicine or a product mentioned in article R. 5121-150 has the services of a reference person for pharmacovigilance.…” There is a difference between the LCPPV (responsable de pharmacovigilance, RPV) and Responsible Pharmacist (Pharmacien Responsible, PR). They can be one and the same person, but they are not the same role. | ||
| Germany | X | LCPPV is required in the Germany (market) The requirement is for marketing authorisation holders so it applies at the time of placing product on the market according to the legislation: §63a of the German Drug Law (AMG) and their responsibility related to product complaints and recalls is described in §19 of the ordinance on GMP Section 63a “Anyone who, in his/her capacity as a pharmaceutical entrepreneur, places finished medicinal products that are medicinal products under the terms of section 2 (1) or subsection (2) no. 1 on the market, must appoint a qualified person who is resident in a Member State of the European Union, who has the required expert knowledge and the reliability necessary for exercising his/her function (graduated plan officer) to set up and manage a pharmacovigilance system and to collect and evaluate notifications on medicinal product risks that have become known and co-ordinate the necessary measures” | ||
| Greece | X | LCPPV is required in the Greece. (approval) Referring to the Ministerial Decree no. Δ.ΥΓ3α/Γ.Π. 32221 ΦΕΚ 1049/29-04-2013, the Greek national competent authority EOF has stated that the marketing authorisation holder must ensure that a local qualified person for pharmacovigilance in Greece is appointed by the EU QPPV. To appoint the LCPPV in Greece, contact details should be sent via email to adr@eof.gr The nomination letter should include: Full name, Qualification, Short CV, Telephone number for communication (company’s and 24-hour availability), Fax number and Email | ||
| Hungary | X | LCPPV is required in the Hungary. (market) According to the agency website and 15/2012 Regulation of Ministry of Human Resources on pharmacovigilance of human medicinal products the marketing authorisation holders should appoint a national contact person in case the residence of responsible person for pharmacovigilance (EU QPPV) is outside of Hungary. It is specified on the website that the requirement for an LCPPV only apply when the product is on the Hungarian market (Thank you Hungary for clarifying this as one of very few EU countries) | ||
| Ireland | – | – | – | No national requirement for the nomination of a local pharmacovigilance contact person. |
| Italy | X | LCPPV is required in the Latvia. (approval) Italy doesn’t formally require nomination of a local national contact person for pharmacovigilance (LCPPV). The EU QPPV can be registered as the contact in Italy if the QPPV speak Italian as all communication and databases in Italy are in Italian. For most practical purposes an Italian LCPPV is therefore required The EU QPPV (if Italian speaking) or a LCPPV must register in the national pharmacovigilance database (NPhVD). All information in the NPhVD are in Italian language. There are more details on the AIFA website. | ||
| Latvia | X | LCPPV is required in the Latvia. (approval) The requirement is specified for marketing authorisation holders so it will apply when approval is granted According to Regulation No. 47 Pharmacovigilance Procedures the marketing authrisation holder must appoint a national level contact person | ||
| Lithuania | – | – | – | LCPPV is not required in Lithuania The EMA document on LCPPV assignments says that a contact person may be requested but the Pharmaceutical Law of the Republic of Lithuania does not seem to contain any such provision |
| Luxembourg | X | LCPPV is required in Luxemburg (application) This requirement is not really stated anywhere and the legislation is ambiguous but normally Belgium and Luxemburg are managed together by the same LCPPV. Therefore the same rules as for Belgium is applied The referenced legislation for appointment of LCPPV in the EU LCPPV assignment document is Grand-Ducal Regulation of 15 December 1992 relating to the marketing of medicinal products however this document does not mention the role of LCPPV. To register the LCPPV a LCPPV registration form must be filled and returned by email to pharmacovigilance@ms.etat.lu or by mail to Divisionde la pharmacie et des médicaments, 20, rue de Bitbourg, L-1273 LuxembourgHamm, Grand Duchy of Luxembourg. | ||
| Malta | – | – | – | LCPPV is not required in Malta Only required if specifically mandated. According to national legislation. In the Guidance Notes for Pharmaceutical Companies on Pharmacovigilance Obligations for Medicinal Products for Human Use (note this a downloaded file from the agency) The Medicines Authority may request the nomination of a contact person for Pharmacovigilance issues at national level, reporting to the qualified person responsible for pharmacovigilance activities. Unless specifically requested, it is the prerogative of each company to decide on the nomination of a person for pharmacovigilance. |
| Netherlands | X | LCPPV is required in the Netherlands. (market) The requirement is specified for marketing authorisation holders. It applies at the time the product is on the market. The legal requirement is explained on the MEB website for local contact person The national contact person for pharmacovigilance: – acts as contact person with the authorities – acts as contact person for patients and medical healthcare practitioners – should be appointed at the moment that a marketing authorisation holder will market a product in the Netherlands. | ||
| Poland | X | LCPPV is required in the Poland (approval) The requirement is for marketing authorisation holders. It applies at the time the product is approved. The legal requirements can be found on the agency website: Announcement of the President of the Office of 1 August 2014 on the indication of a contact person in the field of supervision over the safety of the use of a medicinal product. | ||
| Portugal | X | LCPPV is required for Portugal (approval) The requirement is for marketing authorisation holders so it would apply from the time an EU market authorisation is granted according to circular from Infarmed to marketing authorization holders “Contact person for pharmacovigilance issues at national level” No. 145/CD/8.1.6 published on 25th June 2013 General information can be found in the National Legislation, Decree-Law n.º 176/2006, 30 August, in the present actualization, article n.º 170, number 5 | ||
| Romania | – | – | – | LCPPV is not required in Romania Only required if specifically mandated. According to national legislation (Law 95/2006 with subsequent amendments, art.815 alin.5) the National Agency for Medicines and Medical Devices (NAMMD) may request the nomination of pharmacovigilance contact person at national level for national pharmacovigilance aspects who should report the activity to EU QPPV level |
| Slovakia | X | LCPPV is required in Slovakia (approval) According to the national legislation law on medicines and medical devices 362/2011, §68, art.14 the agency may require a market autorisation holder to assign a LCPPV. The State Institute for Drug Control in Slovakia have decided to require nomination of a contact person responsible for pharmacovigilance issues at national level which is subject to EU-QPPV. It is often practical to use the same LCPPV for both the Czech Republic and Slovakia | ||
| Slovenia | – | – | – | LCPPV is not required in Slovenia Only required if specifically mandated it must be assigned. The law on drugs, which implements the new PhV regulation, it is written that it is possible but not obligatory to have pharmacovigilance contact person in Slovenia (for human and veterinary medicinal products). The Public Agency of the Republic of Slovenia for Medicinal Products and Medical Devices (JAZMP) has the possibility to require contact person for individual cases. The Medicinal Products Act, Article 133 (duties of the marketing authorization holder) has more details |
| Spain | X | LCPPV is required in Spain (market) National responsible for pharmacovigilance (contact person for pharmacovigilance as per our Royal Decree) is required according Royal Decree 577/2013 only for human products. | ||
| Sweden | – | – | – | No national requirement for the nomination of a local pharmacovigilance contact person. |
| United Kingdom | EU QPPV registration and assignment of LCPPV | LCPPV or QPPV is required in UK (application) The rules in the UK are in flux. Below is a summary of the current understanding of the requirements based on the information on the MHRA website The UK require the assignment of a UK QPPV at the time of UK MA application very similar to the requirement in the EU for a QPPV. If an MAH only has a Nationally Approved Product (NAP) in the UK they must have a UK QPPV. If an MAH has MAs already approved in the EU where there has to be an EU QPPV, the EU QPPV will be responsible for the products in the UK too. It is complicated but it is in order to solve the problem with maintaining approvals in Northern Ireland after EU-Exit. Where the EU QPPV functions as UK QPPV a LCPPV residing the in the UK needs to be assigned. If the UK QPPV resides in the UK there is no requirement for LCPPV. | ||
| Switzerland | Can be EU QPPV and must be assigned at MA application | LCPPV or QPPV is required in Switzerland (application) EU QPPV can function as LCPPV for Switzerland (not part of EU or EEA) if the EU QPPV agrees to take on the responsibility for the Swiss PV requirements that are described in general terms in the Therapeutic Products Act, (TPA) article 59 that specifies that a safety reporting system must be in place and that include the role of a Qualified Person for Pharmacovigilance which must be registered at the time of application for market authorisation in Switzerland. There are more details on the FAQ on the Swissmedic website |
Leave a Reply