This content applies to human and veterinary medicines.
Good manufacturing practice
(GMP) describes the minimum standard that a medicines manufacturer must meet in their production processes. The European Medicines Agency (EMA) coordinates inspections to verify compliance with these standards and plays a key role in harmonising GMP activities at European Union (EU) level.
Any manufacturer of medicines intended for the EU market, no matter where in the world it is located, must comply with GMP.
GMP requires that medicines:
Guidance is available for
marketing authorisation holders
, manufacturers and importers of human and veterinary medicines on adaptations to the regulatory framework to address challenges of the
COVID-19 pandemic
, including with
GMP certificates
and
inspections
:
|
In this context, for sites in and outside the European Economic Area (EEA), GMP certificates and time-limited manufacturing and import authorisations are
automatically extended until the end of 2023.
|
This does not waive manufacturers' and importers' obligations to comply with
GMP standards
.
For new sites and facilities within and outside the EEA that have not been inspected or where an inspection is required, a remote inspection may be carried out. On-site inspections will resume as soon as feasible.
EU authorities may not be able to conduct inspections in some
non-EU countries
where
travel restrictions
are in force. Restrictions can include measures such as quarantines.
For such cases as described above, delays may occur in the evaluation procedure for a
marketing authorisation
, if this requires a pre-authorisation GMP inspection of a proposed manufacturing and / or control site.
Applicants are strongly advised to consider the potential impact of travel restrictions on inspections required for their
marketing authorisation
application. In such scenarios, they can mitigate them by:
-
if possible, identifying and including manufacturing and / or control sites with no travel restrictions;
-
liaising with the relevant national authorities where the sites are located to verify whether existing restrictions can be waived or eased.
Please consult the chapter dedicated to inspections in the document below.
The guidance was agreed by the
GMP/GDP Inspectors Working Group
coordinated by EMA, the European Commission, the
European medicines regulatory network
and endorsed by the
EU Executive Steering Group on Shortages of Medicines Caused by Major Events
. It is updated as the pandemic develops.
For more information, see:
The Agency has a coordinating role for GMP inspections of manufacturing sites for medicines whose
marketing authorisation
in the EU is submitted through the
centralised procedure
or as part of a
referral
procedure.
The Agency also plays a key role in coordinating and
harmonising
GMP activities at an EU level. It is involved in:
-
coordinating the preparation of new and revised guidance on GMP;
-
ensuring common interpretation of EU GMP requirements and related technical issues;
-
developing EU-wide procedures on GMP inspections and related activities;
-
facilitating cooperation between Member States for inspections of manufacturers in third countries.
Marketing authorisation holders
and applicants need to use EMA's
IRIS system
to communicate with EMA on
GMP inspections
requested by the Agency’s scientific committees.
Using IRIS for GMP inspections improves efficiency by harmonising and automating processes and re-using
master data
held by EMA. It also simplifies retrieving and reporting data.
More information on the use of EMA's IRIS system:
IRIS guide for applicants - How to create and submit scientific applications, for industry and individual applicants
(PDF/2.33 MB)
Manufacturers and importers located in the European Economic Area (EEA) must hold an authorisation issued by the
national competent authority
of the Member State where they carry out these activities.
They must comply with EU GMP to obtain a manufacturing or import authorisation. They can ensure that they meet all their legal obligations by following the EU GMP
guidelines
.
Importers are responsible to ensure that the
third country
manufacturer they are importing from comply with GMP.
Marketing authorisation
applicants are responsible to ensure that the proposed manufacturing sites included in the
marketing authorisation application
comply with GMP. For more information, see section 5.2 Inspections of the
Pre-authorisation guidance
.
Manufacturers of
active substances
intended for the manufacture of human medicines for the EU market must register with the
national competent authority
of the Member State where they are located.
Active substance
manufacturers must comply with GMP. In addition, the manufacturer of the finished product is obliged to ensure that the
active substances
they use have been manufactured in compliance with GMP.
Importers of
active substances
intended for the EU market are also required to register. In addition, each consignment needs to be accompanied by a confirmation by the
competent authority
of the country where it is produced that it conforms to GMP standards equivalent to those in the EU, unless a waiver applies.
In the EU,
national competent authorities
are responsible for inspecting manufacturing sites located within their own territories.
Manufacturing sites outside the EU are inspected by the
national competent authority
of the Member State where the EU importer is located, unless a
mutual recognition agreement
(MRA) is in place between the EU and the country concerned. If an MRA applies, the authorities mutually rely on each other's inspections.
If products are imported directly into more than one Member State from a manufacturing site outside the EU, there may be more than one
national competent authority
responsible for inspecting it. EMA facilitates cooperation between the authorities concerned in supervising the site.
EU competent authorities plan routine inspections following a risk-based approach, or if there is suspicion of non-compliance.
EudraGMDP
is a publicly accessible EU database which contains manufacturing and import authorisations, registration of
active substance
manufacturers, GMP certificates and non-compliance statements.
After inspecting a manufacturing site, EU competent authorities issue a GMP certificate or a non-compliance statement, which is entered in the EudraGMDP database.
EMA maintains a compilation of GMP and
good distribution practice
(GDP) inspection-related
procedures and forms
agreed by all Member States. This facilitates cooperation between EU Member States and supports harmonisation and exchange of inspection-related information.
It covers the basis for national procedures that form part of the national inspectorates' quality systems:
EMA published the Word and PDF versions of some of the templates for the convenience of inspectorates
Important
The forms and templates should be downloaded and saved first before being completed, using for example “Save target as” function. To report any technical issues with the form, please use the
EMA Service Desk
portal.
Revision of template for serious GMP non-compliance
EMA's
GMP/GDP Inspectors Working Group
is discussing actions required after an inspection concludes that a manufacturing site does not comply with GMP, specifically where this can lead to a
shortage of critical medicines
. EMA has held a public consultation on an updated template for GMP non-compliance statement in 2018:
Plasma master file (PMF) inspections
For products derived from blood or blood plasma, EMA is responsible for coordinating inspections of the blood establishments in which collection, testing, processing, storage and distribution is carried out under the PMF certification procedure.
For more information on the PMF certification procedure, see
Plasma master files
.
Vaccine antigen master file (VAMF) inspections
EMA is responsible for coordinating inspections of vaccine antigen manufacturing sites under the VAMF certification procedure.
For more information on the VAMF certification procedure, see
Vaccine antigens
.
The EU has signed
mutual recognition agreements
on GMP inspections with regulatory authorities outside the EU. This allows EU authorities and their counterparts to:
-
rely on each other's GMP inspections;
-
waive batch testing of products on entry into their territories;
-
share information on inspections and quality defects.
-
The scope of each agreement differs.
