Preparación del Electronic Application

Form (e-AF)
CEP en Registro de Medicamentos y Regulatory Affairs
TEMA 2.1: PrEPArACión dEl E-AF

ÍndiCE

inTrOdUCCión 3

1. GEnErAlidAdEs sObrE El ElECTrOniC APPliCATiOn FOrM 5

2. COMO TrAbAjAr En El E-AF 7

3. sECCiOnEs y qUE COnTEnidO dEl E-AF 9

Declaration anD signature 10
tYPe oF aPPlication 13
MarKeting autHorisation aPPlication Particulars 37
scientiFic aDVice 54
otHer MarKeting autHorisation aPPlication 55
anneXeD DocuMents 58
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 3
TEMA 2.1: PrEPArACión dEl E-AF

inTrOdUCCión

AnTECEdEnTEs

esubmission roadmap y e-AF

La versión final de las HMA (Heads of Medicine Agencies) eSubmission

roadmap (hoja de ruta) fue respalada por el “EU Telematics Manage-
ment Board” el 1 de octubre de 2014, y describe la situación actual de
las solicitudes electronicas en la Unión Europea y los temas a tratar en el
futuro cercano. La Hoja de ruta incluye ciertas iniciativas tales como el
formato de los dossieres, soluciones acerca de los portales electrónicos
y el Application Form.

Con respecto al Application Form (formulario de solicitud) se decidio

cambiar del formato word, a un formato elecrónico que usa técnologia
PDF para capturar la información y técnología XML para transferir la in-
formación, que es lo que llamamos e-Application Form (e-AF).

El contenido del Application Form no varío, pero se incluyo la posibilidad

de importar y exportar datos electrónicos, realizar autocopiado de es-
tos datos dentro del AF y acceso online a catálogos estandarizamos de
terminos. Este documento esta validado electrónicamente y permite un
chequeo antes de su envio.

Este nuevo e-AF, se adopto para las solicitudes iniciales de registro de

medicamentos, variaciones y revalidades quinquenales de medicamen-
tos de uso Humano y Veterinarios.

Todo con el objetivo de reducir las tareas administrativas tanto para

los laboratorios farmacéuticos y las Agencias Reguladoras, y dar apoyo
a la necesidad creciente de incrementar la calidad de los datos que se
incluyen en los Application Form.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 4
TEMA 2.1: PrEPArACión dEl E-AF

inTrOdUCCión

Tal y como se describe en el eSubmission roadmap para el e-AF se han

seguido los siguiente pasos para su implementación:

• Paso 1: 1 de julio de 2015, uso obligatorio del e-AF en Proced-

imiento Centralizado Humanos y Veterinarios

• Paso 2: 1 de enero de 2016, uso obligatorio del e-AF para todos

los procedimientos

El objetivo a futuro y siguientes pasos, es integrar el eAFs, posiblemente

usando técnologia diferente en un Portal unico de presentación en 2018,
tal como viene descrito en la hoja de ruta europea.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 5
TEMA 2.1: PrEPArACión dEl E-AF

1. GEnErAlidAdEs sObrE El ElECTrOniC

APPliCATiOn FOrM

El “electronic Application Form” es un formulario electrónico único europeo,

(que utiliza tecnología PDF para capturar la información y XML para trans-
ferirla), preparado para la solicitud de Nuevas Autorizaciones de Comer-
cialización de Medicamentos de Uso Humano y Medicamentos Veterinar-
ios, Variaciones de la Autorización de Comercialización y Revalidaciones.

Dicho formulario será de obligada aplicación a partir del 01 de enero de

2016 para todo tipo de procedimientos de registro, (acorde a la hoja de
ruta de la red de Agencias Europea), centralizados, MRP, DCP y proced-
imientos nacionales.

Los distinos electronic Application Form están disponibles para su des-

carga en Esubmission o en la Sede electrónica de la AEMPS

• EU Electronic Application Forms eSubmission website

• https://sede.aemps.gob.es/usoHum/regMed/raefar.htm (HUMANA)

• https://sede.aemps.gob.es/usoVet/raevet.htm (VETERINARIA)

Encontraremos información y documentos de utilidad acerca del elec-

tronic Application Form, en el siguiente enlace: http://esubmission.ema.
europa.eu/eaf/index.html se encuentran documentos tales como:

• Guidance documents.-regulatory: User Guide for the electronic

application form for a marketing authorisation (Human) User Guide
for the electronic application form for a marketing authorisation (Vet-
erinary) (Guías que facilitan el trabajo de los solicitantes a la hora de
cumplimentar los e-AF, como parte de una solicitud de autorización
de comercialización de un medicamento de uso humano / medica-
mento veterinarios)
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 6
TEMA 2.1: PrEPArACión dEl E-AF

1. GEnErAlidAdEs sObrE El ElECTrOniC

APPliCATiOn FOrM

• Guidance documents.-Technical: Practical user guide for elec-

tronic Application Forms (eAF) for human and veterinary products
in the EU (Proporciona un apoyo práctico y técnico sobre el uso de
los e-AF para medicamentos de uso humano y veterinario) Nota: Se
recomienda consultar las Guías regulatorias y técnicas en paralelo

• questions and Answers (FAq´s): User Guidance Human &

Vet: http://esubmission.ema.europa.eu/eaf/docs/eAF%20Question
%20and%20Answers%2014.6.2016.pdf

• También se recomienda consultar el siguiente documento de utili-

dad.electronic Application Form training for industry: Webi-
nar for industry - Use of Human and Veterinary e-AF http://
esubmission.ema.europa.eu/eaf/docs/eAF%20training%20Jan%20
2016%20industry(2).pdf
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 7
TEMA 2.1: PrEPArACión dEl E-AF

2. COMO TrAbAjAr En El E-AF

Cuando abro el documento

Tardaremos un tiempo en abrirlo ya que esta conectado a web services

y las listas desplegables se cargan desde el EUTCT y existen en el eAF
“‘business validation rules’ que hacen que este documento sea lento y
pesano.

Los campos de busqueda no funcionarán si no se dispone de coneccion

internet (como es el Active substance, Excipients and ATC code).

La EMA trabaja constantemente para mejorar, el acceso y el tiempo de

respuesta del e-AF

Al abrir el formulario, puede que aparezca el mensaje “Algunas carac-

terísticas han sido desactivadas para evitar posibles riesgos de segu-
ridad. Active estas opciones solo si confía en el documento” pulsar en
Opciones/Confiar siempre en este documento.*

navigación en el documento

Al ir de sección en sección, clicando con el raton en las cajas azules

section name.

Cuando vamos dentro de este campo no redirije directamente a la tabla

de contenidos donde podrmos navigar por todo el documento.

integración del AF en el dossier de registro

Solo podrá incluirse el PDF final firmado y creado de forma electronica

en el dossier de registro.

El formulario disponen de una opción de autovalidación, para confirmar,

que el formulario ha sido correctamente cumplimentado, (ultima pagina
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 8
TEMA 2.1: PrEPArACión dEl E-AF

2. COMO TrAbAjAr En El E-AF

del eAF: “FORM VALIDATION” así como una opción de bloqueo para
asegurar que el contenido del formulario no se modifique.

Será importante realizar ambas operaciones antes de proceder con el

envío para su presentación a las autoridades nacionales.

Los datos XML data se podrán extraer del archivo pdf. Esta acción se
realizará por las autoridades sanitarias cuando reciban el dossier de
registro.

Por tanto los laboratorios a la hora de presentar el dossier solo deben

adjuntar el pdf del e-AF y no el documento XML por separado.

El formulario dispone de un seguro que una vez firmado este no pueda

modificarse.

No podrán incluirse más documentos dentro de este pdf, ni hacer hy-

perlinks.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 9
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

A continuación se describen todas las secciones del e-AF y su contenido,

esta información es la que las Autoridades Sanitarias quieren conocer
para que pueda presentarse y autorizarse un medicamento.

El e-AF solo esta disponible en Inglés y debe completarse en Inglés (solo

se aceptará el cumplimiento de la información en Español en el caso de
presentar un registro nacional en España y solo ciertos campos libres
podrán completarse en Español) y por tanto el resto de la información
aqui descrita viene en inglés.

El e-AF consta de los siguientes apartados:

Declaration and signature

1. TYPE OF APPLICATION

2. MARKETING AUTHORISATION APPLICATION PARTICULARS

3. SCIENTIFIC ADVICE

4. OTHER MARKETING AUTHORISATION APPLICATION

5. ANNEXED DOCUMENTS
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 10
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

Declaration anD signature

declaration and signature

In this declaration, data must be identical to the information provided

in Sections 2.1, 2.2, 2.4 and 2.6, as well as the supportive documents
provided (e.g. annexes to the application form, proposed product infor-
mation, other Modules of the dossier).

When this section is completed the data should be populated to corre-

sponding fields in other sections of the application form by clicking on
the respective push-button “Populate data”.

Product (invented) name

In case of an application under the mutual recognition (MRP) or decen-

tralised (DCP) procedure, the product name used in the reference Mem-
ber State (RMS) should be listed. A list of the different proposed invented
names and marketing authorisation holders in the concerned member
states should be appended to the application form in annex 5.19.

For centralised procedure, the invented name should be agreed by Name

Review Group prior submission. Please refer to the EMA website for fur-
ther information: http://www.ema.europa.eu/ema/

Pharmaceutical form

The pharmaceutical form should be chosen from the list, which includes
the pharmaceutical forms described in the Standard terms published in
the European Pharmacopoeia that provides standardised nomenclatures
and quality standards for medicinal substances and products (https://
www.edqm.eu/en/standard-terms-590.html). Only the full term should
be mentioned (not the short term).
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 11
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

Declaration anD signature

If the application for several pharmaceutical forms is made with a com-

bined application form, the pharmaceutical form field should be dupli-
cated and all pharmaceutical forms included.

strength (s)

Active substance(s)

The two fields “Strength” and “Active substance” should be considered

as linked and corresponding values listed in the same order for both
fields. Strength is to be entered as a text and active substance selected
from the drop-down list (based on a controlled dictionary).

To see the drop-down list click on “Add Active Substance(s)”. If more

than one “Active Substance”is contained, duplicate the field by clicking
on +.

If the concerned pharmaceutical form has several strengths that are

applied for in the same application form, the field should be duplicated
and all strengths included (only applicable to centralised procedures). If
the product contains more than one active substance, each active sub-
stance should be added.

Applicant

For MRP and DCP applications, the applicant should be the same as the
MAH/Applicant in the RMS.

The name of the applicant should be included in the field ‘Applicant’,

while contact person at the address of the applicant should be indicated
in the fields “Title”, “First Name” and “Surname” of this section.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 12
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

Declaration anD signature

Person authorised for communication, on behalf of the Applicant

Letter of authorisation for communication/signing on behalf of the appli-

cant should be attached in annex 5.4.

Person signing the application form should have the letter of authorisa-
tion referred to above
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 13
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

1. TyPE OF APPliCATiOn

1.1 This application concerns

1.1.1 A Centralised Procedure

Article 3 of Regulation (EC) No 726/2004 defines the eligibility of

applications for evaluation under the centralised procedure through
which medicinal products must or may be authorised by the Union.
The eligibility to centralised procedure should be confirmed by the
CHMP in advance of the submission of the application for the mar-
keting authorisation.

The basis for eligibility should be indicated in line with the CHMP
acceptance/confirmation of the eligibility to centralised procedure,
indicating also the date of acceptance/confirmation of eligibility.
Only one eligibility basis should be indicated (additional information
must be indicated for Advanced Therapy Medicinal Products, as ap-
plicable). If the product falls under ‘mandatory’ eligibility scope, this
scope should be indicated, even if the product falls also under an
‘optional’ scope.

The Appointed Rapporteurs from the concerned Committees should

also be indicated in this section.

For applications for a change to an existing marketing authorisation

leading to an extension as referred to in Annex I of Regulation (EC)
No 1234/2008, it is not necessary to request (re)confirmation of
eligibility and the same basis for eligibility to the centralised proce-
dure as for the original application should be indicated, whenever
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 14
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

possible. If the corresponding original eligibility basis of the product

is obsolete (no longer exists), only ‘Centralised Procedure’ should
be indicated, leaving the eligibility basis tick boxes blank.

Please refer to the website of European Medicines Agency (www.

ema.europa.eu) for further guidance on process for confirmation
of eligibility to centralised procedure and Rapporteur appointment.

1.1.2 A Mutual recognition Procedure

The applicant should indicate the reference Member State, de-

tails of the marketing authorisation (date and number), procedure
number, and for each “wave” of mutual recognition procedure con-
cerned Member State(s) and the proposed (or agreed) common
renewal date.

The procedure number is the Mutual Recognition Procedure num-

ber allocated by the RMS. “First Use” means the first Mutual Recog-
nition Procedure.

All the concerned Member states should be indicated.

“Repeat use” means a new use (“wave”) of the same mutual recog-
nition or decentralised procedure made to include new concerned
member state(s).

When applying for a repeat use, the applicant only complete infor-
mation regarding the new CMS included in this specific wave.

Further information on previous applications should be provided in

section 4 of the application.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 15
TEMA 2.1: Preparación del e-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

1.1.3 A decentralised Procedure

The applicant should indicate reference Member State, procedure num-

ber concerned Member State(s) and proposed common renewal date.

For repeat-use of decentralised procedure, please complete sec-

tion 1.1.2.

1.1.4 A national Procedure

In the case of a national application, the application number is al-

located by some member states prior to the official application and
therefore should be indicated.

No specific format can be given for this application number.

1.2 Orphan Medicinal Product information

1.2.1 Has Orphan designation been applied for this medic-

inal product?

Regulation (EC) No 141/2000 and Commission Regulation (EC) No

847/2000 foresee incentives for development of medicinal products
for rare diseases (orphan medicinal products) including market ex-
clusivity, protocol assistance, eligibility for initiatives which support
research and development, access to the centralised procedure
and the possibility to request fee reductions from the EMA. Me-
dicinal products eligible for these incentives are clearly identified
through a procedure for orphan designation.

The applicant should note whether an application for orphan des-

ignation, for the medicinal product concerned, has ever been
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 16
TEMA 2.1: Preparación del e-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

submitted to the EMA for the condition that is the subject of the
application for marketing authorisation, and if ‘yes’, the EMA proce-
dure number (EMEA/OD/XXX/year or EMA/OD/XXX/year) should be
provided together with details of the status as follows:

• if a designation application is pending, tick this option;

• if orphan designation has been granted, note details of the date

of designation (i.e. date Commission Decision on designation
was adopted), whether or not the designation was based on
the ‘significant benefit’ criterion in accordance with Article
3(1)(b), Regulation (EC) No 141/2000, and the Number in the
Community Register of Orphan Medicinal Products (EU/X/year/
XXX). A copy of the Commission Decision on orphan designation
should be attached as Annex 5.18;

• if orphan designation has been refused, provide the date of the

Commission Decision refusing the designation and its reference;

• if an application for designation has at any time been submitted

and subsequently withdrawn, note the date of withdrawal by the
sponsor.

1.2.2 information relating to orphan market exclusivity

This section is to be completed for all applications, whether

the applicant is the holder of an orphan designation or not,
and regardless of the legal basis of the application being
submitted (e.g. including applications under Art 10(1)).

In accordance with Article 8 of Regulation (EC) No 141/2000, when

an orphan medicinal product is authorised throughout the EU, a
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 17
TEMA 2.1: Preparación del e-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

10-year period of market exclusivity commences from the date of the

granting of the marketing authorisation and protects orphan medici-
nal product for the authorised ‘orphan’ therapeutic indication. In cer-
tain cases, this market exclusivity period can be extended to 12 years
or reduced to 6 years. During the market exclusivity period similar
medicinal products will not be granted a marketing authorisation for
the same therapeutic indication unless the marketing authorisation
holder for the orphan product gives consent, is unable to supply
sufficient quantity of the medicinal product, or the second applicant
demonstrates that although ‘similar’, the medicinal product is ‘clini-
cally superior’ to the already authorised orphan medicinal product.

The definition of ‘similar’ and ‘clinically superior’ in this context is

defined in Article 3 of Commission Regulation (EC) No 847/2000.

All applicants are requested to indicate whether or not any other

medicinal product has been granted orphan designation in the EU
for the condition relating to the indication proposed in the applica-
tion for marketing authorisation.

To complete this section of the application form the applicant should

check the “Active” part of “Community Register of orphan medic-
inal products for human use” that is available on the Website of
the European Commission (http://ec.europa.eu/health/documents/
community-register/index_en.htm).

If the condition relating to the proposed therapeutic indication pro-

posed in the application has been the subject of an orphan desig-
nation:
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 18
TEMA 2.1: Preparación del e-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

• all corresponding EU orphan designation number(s) (EU/X/year/

XXX) should be provided

• the applicant should indicate whether or not any designated or-

phan medicinal product(s) has been granted a marketing au-
thorisation in the EU.

If any of the designated orphan medicinal products have been

granted a marketing authorisation:

• for each of the authorised orphan medicinal product(s) the ap-

plicant should specify, repeating the fields as necessary:

• The therapeutic indication(s) of the authorised product for

a condition which is related to the indication proposed in
the application that is being submitted;

• Name, pharmaceutical form(s) and strength(s) of the au-

thorised product;

• Name of the marketing authorisation holder;

• Marketing authorisation number(s);

• Date of authorisation.

• the applicant should indicate whether or not the medicinal prod-

uct which is the subject of the application for marketing authori-
sation is considered ‘similar’ to any of the authorised orphan
medicinal products.

• a critical report should be submitted in module 1.7.1 of the ap-

plication for marketing authorisation addressing the possible
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 19
TEMA 2.1: Preparación del e-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

similarity with the authorised orphan medicinal product(s) and

concluding on “similarity” or “non-similarity”.

Article 3 of Commission Regulation (EC) No 847/2000 defines sim-

ilar medicinal product as a medicinal product containing a similar
active substance or substances as contained in a currently autho-
rised orphan medicinal product, and which is intended for the same
therapeutic indication. It also defines similar active substance
as an identical active substance, or an active substance with the
same principal molecular structural features (but not nec-
essarily all of the same molecular features) and which acts via the
same mechanism. Based on the above mentioned definitions, the
assessment of similarity between two medicinal products takes into
consideration the following criteria:

• Principal molecular structural features,

• Mechanism of action and

• Therapeutic indication.

If significant differences exist within one or more of these criteria,

the two products will not be considered as similar.

If the medicinal product, which is the subject of the application for mar-
keting authorisation is deemed to be “similar” to one or more orphan
medicinal product(s) covered by orphan market exclusivity provisions:

• the applicant should submit in module 1.7.2 of the application

for marketing authorisation a justification for each of the “sim-
ilar” orphan medicinal product(s) that one of the derogations
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 20
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

laid down in Article 8.3, paragraphs (a) to (c) of the Regulation

(EC) No 141/2000 applies, that is:

(a) the holder of the marketing authorisation for the orphan

medicinal product has given his consent to the applicant of
this application, or

(b) the holder of the marketing authorisation for the orphan

medicinal product is unable to supply sufficient quantities of
the medicinal product, or

(c) the applicant can establish in the application that their

medicinal product, although similar to the orphan medicinal
product already authorised, is safer, more effective or other-
wise clinically superior.

Further guidance can be found in the Guideline on aspects of the

application of Article 8(1) and (3) of Regulation (EC) No 141/2000:
Assessing similarity of medicinal products versus authorised orphan
medicinal products benefiting from market exclusivity and apply-
ing derogations from that market exclusivity (http://ec.europa.eu/
health/files/orphanmp/doc/c_2008_4077_en.pdf)

1.3 Application for a change to existing marketing authorisa-

tion leading to an extension as referred to in Annex i of regu-
lation (EC) no 1234/2008

Certain changes to a marketing authorisation are considered to funda-

mentally alter the terms of a marketing authorisation and therefore can-
not be considered as a variation. For these changes, set out in Annex I of
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 21
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

Regulation (EC) 1234/2008, a new application must be made that shall

be evaluated in accordance with the same procedure as for the initial
marketing authorisation to which it relates.

If the applicant of the present application ticks “Yes,” he must be the

same as the marketing authorisation holder of the existing marketing
authorisation. Applications for changes or additions falling under the
scope of Annex I can only be submitted for the existing marketing au-
thorisation by the marketing authorisation holder.

An application for an extension is made under the same legal basis as

the original MA (see section 1.4 of the Application Form).

1.3.1 Changes applied for

For extension applications the applicant should specify which of

the changes set out in Annex I of Regulation (EC) 1234/2008 this
application concerns:

• a qualitative change in declared active substance not defined as

a new active substance (indicating the type of change),

• change in bioavailability,

• change in pharmacokinetics,

• change or addition of a new strength/potency,

• change or addition of a new pharmaceutical form,

• change or addition of a new route of administration.

Several of the changes above are possible to be included in a single

application form if applied for at the same time. All of the changes
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 22
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

applied for should be indicated therefore all relevant boxes should be

ticked (e.g. change of pharmaceutical form and change of strength).

The European Commission has published a guideline to clarify the

terms ‘pharmaceutical form’ and ‘strength’ and to include relevant
examples for this classification: (http://ec.europa.eu/health/files/
eudralex/vol-2/c/v2c_ea_v 10_2003_en.pdf).

This guideline on categorisation should be read in conjunction with

the European Directorate for the Quality of Medicines and Health-
care (EDQM) guidance: Standard terms: Introduction and guidance
for use (http://www.edqm.eu/medias/fichiers/Introduction_Guid-
ance_for_Use.pdf), Regulation (EC) No 1234/2008 and Regulation
(EC) N° 1901/2006.

In case of doubt, the MAH is advised to contact the concerned Com-

petent Authority in advance of the submission.

For changes relating to the active substance where the active sub-
stance is viewed as a “new active substance” as defined in Chapter
I – Volume 2A of the Notice to Applicants, application for an inde-
pendent marketing authorisation should be made (not an extension
application).

1.3.2 Article 29 application

This subsection should be filled in for applications submitted to the

EMA according to Article 29 of Regulation (EC) No 1901/2006, where
an extension application is made for use in the paediatric population
for a new pharmaceutical form or a new route of administration.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 23
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

In such case the applicant should indicate whether the application con-
cerns new pharmaceutical form and/or new route of administration.

Existing marketing authorisation

For applications that are a change to existing marketing authori-

sation, the applicant should provide information regarding existing
marketing authorisation in the European Union / Member State
where the application is made:

• (Invented) name of the product;

• Pharmaceutical forms(s);

• Strength(s);

• Name of the marketing authorisation holder;

• Marketing authorisation number (all marketing authorisation

numbers of each presentation should be given, when applicable).

1.4 This application is submitted in accordance with the

following article in directive 2001/83/EC as amended

This Section should be completed for each application and only one
round box should be ticked.

The applicant should indicate the “legal basis” of their application – the
corresponding Article of Directive 2001/83/EC, according to which the
application is made. Please refer to Notice to Applicants, Volume 2A,
Chapter 1 for further guidance.

For applications for a change to an existing marketing authorisation

leading to an extension as referred to in Annex I of Regulation (EC) No
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 24
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

1234/2008, the legal basis of the extension should be the same as the
one used previously for the existing marketing authorisation. For exten-
sions, cross references to pre- clinical and clinical data of the existing
marketing authorisation could be made.

1.4.1 Article 8(3) application

For applications made according to Article 8(3) of Directive 2001/83/

EC, the applicant should indicate whether it concerns a new active
substance (as of the time of submission) or a known active sub-
stance. In case the claim of a new active substance is made, the
corresponding justification should be provided as Annex 5.23 to the
Application Form and the corresponding box in section 1.4.1 ticked.

1.4.2 Article 10(1) generic application

For applications made according to Article 10(1) of Directive

2001/83/EC the applicant should indicate under:

• “Medicinal product which is or has been authorised in accor-

dance with Union provisions in force (acquis communautaire) for
not less than 6/(8)/10 years in the EEA” – a reference medicinal
product for which regulatory data protection and, if applicable,
orphan market protection periods have expired;

• “Medicinal product authorised in the Union/Member State where

the application is made or European reference medicinal prod-
uct” – a reference medicinal product with the same pharmaceu-
tical form(s) (please see Article 10(2) of Directive 2001/83/EC
regarding immediate release oral forms), strength(s) and route
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 25
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

of administration, on which the product information of the ge-

neric product is based;

• “Medicinal product which is or has been authorised in accordance

with Union provisions in force and to which bioequivalence has
been demonstrated by appropriate bioavailability studies” – a
reference medicinal product used as the reference product in
bioequivalence studies.

All 3 subsections must be filled out, otherwise the Appli-

cant should justify.

The reference medicinal products listed above must belong to the

same Global Marketing Authorisation, contain the same active sub-
stance(s) as the generic product and be authorised on the basis of
a complete dossier. When there are any differences between prod-
ucts indicated under the second and third indent of this section, the
applicant should justify in Module 2 the relevance of the bioequiv-
alence data.

In centralised procedure, European reference medicinal product(s)

should be chosen for first and second indent of this section (not
separate reference products for each Member State).

Please refer to Notice to Applicants, Volume 2A, Chapter 1 for fur-

ther guidance.

For each of the reference medicinal products in this section the appli-
cant should indicate all the particulars listed in the application form:

• (Invented) name of the product

CEP en Registro de Medicamentos y Regulatory Affairs
pag. 26
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

• Pharmaceutical form(s)

• Strength(s)

• Name of the marketing authorisation holder

• Marketing authorisation number

• Date of authorisation

• The EEA (including EU) Member State or EU that has granted

the marketing authorisation

For the product to which the bioequivalence has been demonstrat-

ed the applicant should also indicate the Member State in which the
product has been sourced for the bioequivalence studies and the
references numbers/ EudraCT numbers of those studies.

Further details and justification for the type of application should be

provided in section 1.5.2 of CTD Module 1.

1.4.3 Article 10(3) hybrid application

For applications made according to Article 10(3) of Directive

2001/83/EC the applicant should indicate:

• “Medicinal product which is or has been authorised in accor-

dance with Union provisions in force (acquis communautaire)
for not less than 6/(8)/10 years in the EEA” – medicinal product
for which regulatory data protection and, if applicable, orphan
market protection periods have expired;

• “Medicinal product authorised in the Union/Member State where

the application is made or European reference medicinal product”
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 27
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

– medicinal product, on which the product information of the hy-

brid product is based;

• Differences (several possible) to the reference medicinal product

on which the product information of the hybrid product is based:

• change in the active substance(s),

• change in therapeutic indications,

• change in pharmaceutical form,

• change in strength (quantitative change to the active sub-

stance(s)),

• change in route of administration,

• bioequivalence cannot be demonstrated through bioavailabil-

ity studies.

• If applicable, “medicinal product which is or has been authorised

in accordance with Union provisions in force and to which bio-
equivalence has been demonstrated by appropriate bioavailabil-
ity studies” – medicinal product used as the reference product in
bioequivalence studies.

All subsections must be filled out, otherwise the Applicant

should justify.

For each of the products in this section the applicant should indicate
all the particulars listed in the application form.

The products referred to must belong to the same Global Market-

ing Authorisation, contain the same active substance(s) and be
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 28
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

authorised on the basis of a complete dossier. When there are any

differences between products indicated under second and third in-
dent of this section, the applicant should justify in Module 2 the
relevance of the bioequivalence data.

In centralised procedure European reference medicinal product(s)

should be chosen for first and second indent of this section (not
separate reference products for each Member State).

Please refer to Notice to Applicants, Volume 2A, Chapter 1 for fur-

ther guidance.

Further details and justification for the type of application should be

provided in section 1.5.2 of CTD Module 1.

1.4.4 Article 10(4) similar biological application

For applications made according to Article 10(4) of Directive

2001/83/EC the applicant should indicate:

• “Medicinal product which is or has been authorised in accor-

dance with Union provisions in force (acquis communautaire)
for not less than 6/(8)/10 years in the EEA” – medicinal product
for which regulatory data protection and, if applicable, orphan
market protection periods have expired;

• “Medicinal product authorised in the Union/Member State where

the application is made or European reference medicinal prod-
uct” – medicinal product on which the product information of the
biosimilar product is based;
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 29
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

• Differences (several possible) to the reference medicinal product

on which the product information of the biosimilar product is
based:

• change(s) in the raw material(s),

• change(s) in the manufacturing process(es),

• change in therapeutic indication(s),

• change in pharmaceutical form(s),

• change in strength (quantitative change to the active sub-

stance(s)),

• change in route(s) of administration,

• other changes

• “Medicinal product which is or has been authorised in accor-

dance with Union provisions in force and to which comparabili-
ty tests and studies have been conducted” – medicinal product
used as the reference product in comparability tests and studies.

For each of the products in this section the applicant should indicate
all the particulars listed in the application form.

The reference medicinal product to which comparability tests and

studies have been conducted must be authorised in the EEA. When a
non-EEA authorised comparator has been used for certain clinical or
in vivo non-clinical studies in the comparability programme, it must
be clearly identified in Module 1.5.2 but should not be additionally
listed under third indent of this section of the application form. The
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 30
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

“Guideline on similar biological medicinal products” should be con-

sulted on the acceptability of a Non-EU comparator.

In centralised procedure European reference medicinal product(s)

should be chosen for first and second indent of this section (not
separate reference products for each Member State).

The products referred to must belong to the same Global Marketing

Authorisation, and be authorised on the basis of a complete dossier.
When there are any differences between products indicated under
the second and third indent of this section, the applicant should jus-
tify in Module 2 the relevance of the comparability data. Please refer
to Notice to Applicants, Volume 2A, Chapter 1 for further guidance.

Further details and justification for the type of application should be

provided in section 1.5.2 of CTD Module 1.

1.4.5 Article 10a well-established use application

Further details and justification for the type of application should be

provided in section 1.5.1 of CTD Module 1. Please refer to Notice to
Applicants, Volume 2A, Chapter 1 for further guidance.

1.4.6 Article 10b fixed combination application

Please refer to Notice to Applicants, Volume 2A, Chapter 1 for fur-

ther guidance.

1.4.7 Article 10c informed consent application

The applicant should indicate the medicinal product for which the
marketing authorisation holder has provided the consent and from
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 31
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

which all pharmaceutical, preclinical and clinical data form the ba-
sis of the informed consent application. Letter of consent from the
marketing authorisation holder of the authorised product, should be
provided in Annex 5.2 to the application form.

1.4.8 Article 16a traditional use registration for herbal me-

dicinal product

Please refer to Notice to Applicants, Volume 2A, Chapter 1 for fur-

ther guidance.

1.5 Consideration of this application requested under the fol-

lowing article of directive 2001/83/EC or regulation (EC) no
726/2004

1.5.1 Conditional Approval

Article 14(7) of Regulation (EC) No 726/2004 and Commission Reg-

ulation (EC) No 507/2006 are applicable to the centralised proce-
dure only. The applicant should indicate if conditional marketing
authorisation is requested. Further details and justification for the
request should be provided in section 1.5.5 of CTD Module 1.

1.5.2 Exceptional Circumstances

Provision foreseen according to Article 22 of Directive 2001/83/EC

and Article 14(8) of Regulation (EC) No 726/2004. The applicant
should indicate if marketing authorisation under exceptional cir-
cumstances is requested. Further details and justification for the
request should be provided in section 1.5.4 of CTD Module 1.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 32
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

1.5.3 Accelerated review

Article 14(9) of Regulation (EC) No 726/2004 is applicable to the

centralised procedure only. The CHMP agreement on accelerated
procedure should be obtained in advance of the submission of the
application for marketing authorisation. The applicant should in-
dicate if accelerated assessment has been requested and agreed,
together with the date of acceptance by the CHMP.

1.5.4 Article 10(1) of directive 2001/83/EC / Article 14(11)

of regulation (EC) no 726/2004 (one year of market pro-
tection for a new indication)

The applicant should indicate if this request is made. Further details

and justification for the request should be provided in section 1.5.3
of CTD Module 1. Please refer to Notice to Applicants, Volume 2A,
Chapter 1 for further guidance.

1.5.5 Article 10(5) of directive 2001/83/EC (one year of

data exclusivity for a new indication)

The applicant should indicate if this request is made. Further details

and justification for the request should be provided in section 1.5.3
of CTD Module 1. Please refer to Notice to Applicants, Volume 2A,
Chapter 1 for further guidance.

1.5.6 Article 74(a) of directive 2001/83/EC (one year of

data exclusivity for a change in classification)

The applicant should indicate if this request is made. Further details

and justification for the request should be provided in section 1.5.3
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 33
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

of CTD Module 1. Please refer to Notice to Applicants, Volume 2A,

Chapter 1 for further guidance.

1.6 requirements according to regulation (EC) n° 1901/2006

(‘Paediatric regulation’)

For well-established use, generic, hybrid and bio-similar applications and

traditional herbal medicinal products the applicant should indicate that
sections 1.6.1, 1.6.2 and 1.6.3 are not applicable. In such case further
parts of section 1.6 do not need to be filled in.

1.6.1 does the same applicant hold other marketing au-

thorisation(s) for a medicinal product(s) containing the
same active substance(s) in the EEA.

The applicant should indicate whether the applicant (including oth-

er companies belonging to the same mother company or group of
companies or which are “licensees”) holds in the EEA (including EU)
at least one marketing authorisation(s) for a medicinal product(s)
containing the same active substance(s) (falling in the same Global
Marketing Authorisation) as the product for which this application is
made. For applications for a change to existing marketing authori-
sation leading to an extension the existing authorised medicinal
product should be included here.

Specific considerations apply if the same active substance is used

for the purpose of an orphan and a non- orphan product, and the
applicants are advised to consult with EMA in advance of the sub-
mission.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 34
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

If the applicant does not hold existing marketing authorisation(s),

section 1.6.3 should be completed.

If the applicant holds existing marketing authorisation(s), the de-

tails of all such products should be provided in the application form
by providing the particulars listed:

• active substance(s).

• (invented) name of the product,

• pharmaceutical form(s),

• strength(s),

• name of the marketing authorisation holder,

• member State or EU that has granted the marketing authorisation,

• marketing authorisation number (s),

• date(s) of marketing authorisation.

The applicant should indicate whether any of the authorised pro-

duct(s) is protected by a Supplementary Protection Certificate (SPC)
under Regulation (EC) No 469/2009, or a patent qualifying for an
SPC. If ‘yes’, section 1.6.2. should be completed.

1.6.2 does the application relate to a new indication, new

pharmaceutical form or new route of administration?

If this section needs to be completed (please see above), the appli-

cant should indicate whether this application introduces a new indi-
cation, new pharmaceutical form or new route of administration, as
compared to already authorised (in EEA) medicinal products within
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 35
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

same Global Marketing Authorisation. If ‘yes’, section 1.6.3. should

be completed.

1.6.3 PiP and/or waiver

If this section needs to be completed (please see above), the appli-

cant should indicate which of the following applies to this application:

• Paediatric Investigation Plan (PIP) agreed by the Paediatric

Committee (PDCO), indicating also the PIP Decision number(s)
(format P/XXXX/year). This option covers also situation when
PIP includes a waiver for a subset of the paediatric population.

• Product-specific waiver agreed by the PDCO, indicating also the

Waiver Decision number (format P/XXXX/year). This option applies
only if the waiver covers all subsets of the paediatric population.

• Class waiver agreed by the PDCO, indicating also the

Waiver Decision number (format CW/XXXX/year).

These elements should cover all subsets of the paediatric popula-

tion and all indication(s), pharmaceutical form(s) and route(s) of
administration applied for.

For PIP and Product-specific waiver the respective PDCO Opinion

and Summary report should be included in section 1.10 of CTD
Module 1.

1.6.4 Article 30 (PUMA) of the Paediatric regulation

If the application is made according to Art. 30 of the Paediatric Reg-

ulation (EC) No 1901/2006 (Paediatric Use Marketing Authorisation
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 36
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

tYPe oF aPPlication

– PUMA), it should be indicated in this section. The applicant should

confirm that the product is not protected by either a SPC under
Regulation (EC) No 469/2009, or by a patent which qualifies for the
granting of the SPC, and include the PIP decision number(s). PDCO
Opinion and Summary report should be included in section 1.10 of
CTD Module 1.

1.6.5 Has this application been subject to PiP compliance

verification?

The applicant should indicate if this application has been subject

to a PIP compliance verification. If ‘yes’, a reference number of the
document on the compliance should be included, and PDCO com-
pliance report with (where applicable) PDCO opinion or documents
to be included in section 1.10 of CTD Module 1.

The applicant should also indicate any parallel, ongoing or previ-

ous applications containing paediatric data relevant for the full PIP
compliance verification (if applicable). As stated in Volume 2B of
Notice to Applicants, an overview table of the PIP results, indicating
in which application(s) they were/are going to be submitted, status
of the application(s), as well as their location in the present appli-
cation must be included in the Module 1.10.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 37
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

2. MArKETinG AUTHOrisATiOn APPliCATiOn PArTiCUlArs

2.1 name(s) and ATC code

2.1.1 Proposed (invented) name of the medicinal product in

the European Union / Member State/Iceland/Lichtenstein/ Norway

The information is identical to the one in section “Declaration and

signature” (populated automatically).

If different (invented) names in Member States are proposed in the

MRP or DCP, the box should be ticked and these should be listed in
Annex 5.19.

2.1.2 name of the active substance(s)

The information is identical to the one in section “Declaration and

signature” (populated automatically). The active substance should
be declared by its recommended INN, accompanied by its salt or
hydrate form if relevant (for further details, consult the Guideline on
the SmPC). Where no INN is available from EDQM, the name of a
national pharmacopoeia, a common name or scientific name should
be provided. If the INN has not yet been published by the WHO, the
applicant should confirm that the approval of the INN is pending.

Herbal substances / herbal preparations being the active substance

of a (traditional) herbal medicinal product should be declared ac-
cording to the “Guideline on declaration of herbal substances and
herbal preparations in herbal medicinal products / traditional herbal
medicinal products (EMA/HMPC/CHMP/CVM/287539/2005 Rev.1)”
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 38
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

If there is more than one active substance, this field should be du-
plicated.

2.1.3 Pharmacotherapeutic group (Please use current ATC

code)

The applicant should include ATC code agreed by the WHO.

When a WHO agreed ATC code is not available, the most complete
code corresponding to the claimed therapeutic use of the product
should be given. This section should be duplicated where needed.

The two fields “ATC Code” and “Group” are linked and should be
both completed.

When the agreed ATC code is not yet available, but the application
for it has been submitted to the WHO, this should be indicated on
the application form by ticking the box “If no ATC code has been
assigned, please indicate if an application for the ATC code has
been made”.

If an ATC code is agreed and published by the WHO, but it is not

used in the application, a justification should be provided.

in the case of a traditional herbal medicinal product: the

ATC code should be mentioned if available.

2.2 sTrEnGTH, PHArMACEUTiCAl FOrM, rOUTE OF AdMin-

isTrATiOn, COnTAinEr And PACK sizEs

2.2.1 strength and pharmaceutical form (use current list

of standard terms – European Pharmacopeia)
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 39
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

The values for “Pharmaceutical form”, “Strength” and “Active Sub-

stance” fields are populated from “Declaration and signature” section
(please refer to the administrative data section in the user guide).

2.2.2 route(s) of administration:

The route of administration should be chosen from the List of Stan-

dard Terms published by the European Directorate for the Quality of
Medicines and Healthcare (EDQM) https://www.edqm.eu/en/stan-
dard-terms-590.html

2.2.3 Container, closure and administration device(s), in-

cluding description of material from which it is constructed:

The container should be chosen from the List of Standard Terms

published by the European Directorate for the Quality of Medicines
and Healthcare (EDQM).

This subsection should be repeated for each type of pack, also

where two similar types of packages (e.g. two different types of
blister material) are applied for.

• For each type of pack give package materials and different pack-
age sizes.

Note. For mutual recognition and decentralised procedures, all

package sizes authorised in the Reference Member State and in
the Concerned Members States should be listed.

For each container the proposed container, closure and admin-

istration device should be indicated. The subsections should be
repeated, if necessary.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 40
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

Both, container and closure system have a dropdown field to

select the correct option (The dropdown lists are based on a
controlled dictionary).

Indicate if a list of Mock-ups or Samples/specimens sent with

the application is attached, as appropriate (see EMA/CMDh web-
sites). The list should contain short description (names) of mock-
ups or samples/specimens sent and be provided as Annex 5.17
to the application form.

• Proposed shelf life Sections: For each container indicate (if ap-
plicable):

• Proposed shelf life (before first opening of the container)

• Proposed shelf life (after first opening of the container)

• Proposed shelf life (after reconstitution or dilution) Two

sub-sections (rows) have been implemented:

• The row on the left side includes Free text field to enter
numbers

• The row on the right side includes dropdown fields with

standard units list (seconds, minutes, hours,)

The information should be identical to Module 3 and section 6.3

Proposed storage conditions Section and Proposed storage condi-

tions after first opening Section Dropdown field to select the correct
option (The dropdown lists are based on a controlled dictionary)

Proposed storage conditions after opening Section:

CEP en Registro de Medicamentos y Regulatory Affairs
pag. 41
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

Dropdown field to select the storage conditions after first opening

(“Click arrow button”)

The information related to Shelf life / storage conditions will be linked

to one container and type of pack Consequently those sections need
to be replicated for different containers and types of pack.

Indicate if a list of Mock-ups or samples/specimens sent with the

application is attached as appropriate (see EMA/CMDh websites).
The list should contain short description (names) of mock-ups or
samples / specimens sent and be provided (ANNEX 5.17) to the
application form.

Additional rows for “proposed storage conditions / Proposed stor-

age conditions after opening are allowed, where needed

2.2.4 The medical product incorporates, as an integral part,

one or more medical devices within the meaning of Arti-
cle 1(2)(a) of directive 93/42/EEC or one or more active
implantable medical devices within the meaning of Article
1(2)(c) of directive 90/385/EEC

This section is not applicable for administration devices, that are

not integral part of the medicinal product as referred above and
that are listed in section 2.2.3.

2.2.4.1 Manufacturer of the device (for manufacturers out-

side the EEA, please add the authorised representative)

2.2.4.2 Device(s) identification

2.2.4.3 CE mark
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 42
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

If the device(s) have a CE mark, a Manufacturers declaration of

conformity in module 3.2.R of the EU- CTD should be included.

2.2.4.4 Notified Body

For Combined Advanced Therapy Medicinal Products (ATMPs)

the identification of a notified body is always requested (in ac-
cordance with article 9 of Regulation (EC) No. 1394/2007)

For each notified body involved the name and the number of the
Notified body should be included

More information about the Notified Body Number (with the form
nnnn, where n is a number from 0-9) is available at the next link:
http://ec.europa.eu/growth/tools-databases/nando

2.3 legal status

Differences in proposed prescription status are acceptable among Mem-

ber States, in line with national rules in force.

The legal status may differ from one presentation to another but not
all Member States accept more than one legal status at one marketing
authorisation.

Consequently, in mutual recognition and decentralized procedure this

section may need to be replicated where needed and appropriate Mem-
ber State filled in.

In centralised procedure only some of the categories are agreed at the

European level (please see further details in CHMP Guideline on Legal
Status for the Supply to the Patient of Centrally Authorised Medicinal
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 43
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

Products, published on the EMA website). Further sub-categories can be

applied at the national level, based on the main category agreed at the
European level and product information of the concerned product.

2.3.1 Proposed dispensing/classification

2.3.2 For products subject to medical prescriptions

A CHMP Opinion is not given on the first two categories listed in

this section, therefore in centralised procedure applicants should
indicate only third and/or fourth category, if applicable.

2.3.3 supply for products not subject to medical prescription

A CHMP Opinion is not given on these sub-categories, therefore ap-

plicants should not fill in this section for applications in centralised
procedure.

2.3.4 Promotion for products not subject to medicinal pre-

scription

A CHMP Opinion is not given on these sub-categories, therefore ap-

plicants should not fill in this section for applications in centralised
procedure.

2.4 Marketing authorisation holder / Contact persons / Company

2.4.1 Proposed marketing authorisation holder/person le-

gally responsible for placing the product on the market in
the European Union/each Ms
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 44
TEMA 2.1: Preparación del e-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

For MRP/DCP applications if the proposed marketing authorisation hold-

er differs among Member State the fields can be duplicated in order to
indicate more than one proposed marketing authorisation holder.

Proof of establishment of the applicant in EEA must be provided

as Annex 5.3 and must have the same name and address (if men-
tioned) as in the application form.

In centralised procedure, if the applicant has SME status confirmed

by the EMA, the copy of “Qualification of SME Status” should be in-
cluded as Annex 5.7 and the EMA SME number should be indicated
on the application form.

2.4.2 Person/company authorised for communication on

behalf of the applicant during the procedure in the Europe-
an Union/each Ms

In mutual recognition and decentralized procedures, if more than one

person/company is authorized for communication the related fields
can be duplicated in order to indicate more than one person/company.

In centralised procedure, only one contact person can be indicated.

2.4.3 Person/company authorised for communication be-

tween the marketing authorisation holder and the compe-
tent authorities after authorisation if different from 2.4.2 in
European Union/each Ms

In mutual recognition and decentralized procedures, if more than one

person/company is authorized for communication the related fields
can be duplicated in order to indicate more than one person/company.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 45
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

In centralised procedure, only one contact person can be indicated.

2.4.4 summary of the applicant pharmacovigilance system

In mutual recognition and decentralized procedures, if more than

one Qualified person in the EEA for Pharmacovigilancethe is as-
signed and/or for different Member States, related fields can be
duplicated in order to indicate more than one Qualified person and/
or different Member States.

In centralised procedure, only one qualified person can be indicated.

2.4.5 Scientific service of the MAH in the EEA as referred

to in Article 98 of directive 2001/83/EC (for dCP, MrP and
national applications, the contact person in the country
where the application is made)

According to Art. 98 of Directive 2001/83/EC the marketing authori-

sation holder shall establish, within his undertaking, a scientific ser-
vice in charge of information about the medicinal products which he
places on the market. Differences in establishing within MAH under-
taking, a scientific service are acceptable among Member States, in
line with national rules in force.

In centralised procedure a single contact person should be indicat-

ed for the scientific service.

2.5 MAnUFACTUrEr

For each company two “addresses” are described: Address 1 field to enter
building name/number or street and Address 2 field to enter city/town.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 46
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

For manufactures there are two options:

• Option # 1:- The administrative address and manufacture address

are the same

• Option # 2:- The administrative address and manufacture address

are different: In this case administrative and manufacturing facility
address fields are separate

Note: ALL manufacturing and control sites mentioned throughout the whole
dossier (ANNEX 5.8, Module 3.2S. 3.2.P, the Application form section 2.5
and Product Information) MUST be consistent regarding their names, de-
tailed addresses and activities. Sites should not be included in one part of
the dossier and left out in another for the reason of their activity.

For manufacturing sites in section 2.5 of the application form, it is rec-

ommended to enter the EUDRA GMP certificate reference number, if
exists, instead of attaching the GMP certificate in Annex 5.9. Similarly, it
is recommended to enter the EUDRA GMP Manufacturing Authorisation
reference number, if exists, instead of attaching a copy of the manufac-
turing authorisation(s) or other proof of GMP compliance in ANNEX 5.6.

2.5.1.a Authorised manufacturer(s) (or importer(s)) re-

sponsible for batch release in the EEA in accordance with Ar-
ticle 40 and Article 51 of Directive 2001/83/EC (as shown in the
package leaflet and where applicable in the labelling or Annex II of
the Commission Decision):

Several Authorised Manufacturers can be included, if necessary.

The manufacturer country field has a dropdown to select each one,
based on a controlled list of countries
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 47
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

2.5.1.b Official batch release for Blood products and Vac-

cines
Details of the Official Medicines Control Laboratory (OMCL) or lab-
oratory designated for the purpose of official batch release (in ac-
cordance with Articles 111(1), 113, 114(1)-(2) and 115 of Directive
2001/83/EC as amended)

The laboratory country field has a dropdown based on a controlled

list of countries (only site(s) in the EEA)

The phone number (telephone and telefax) of the relevant function-

al office including the international area codes should be included

2.5.1.1 Contact person in the EEA for product defects

and recalls

For 24 H Telephone and Telefax fields, the phone number of the

relevant functional office including the international area codes
should be included.

Only one contact person per marketing authorisation should be

indicated

2.5.1.2 batch control/Testing arrangements Unless a MRA

or other Community arrangement is in operation with the third
country concerned, applicants are reminded that each produc-
tion batch has to undergo all the controls required by Art 51 of
Directive 2001/83/EC as amended, in the EEA .

A brief description of control tests carried out by the laborato-

ry (ies) concerned should be selected from the dropdown field
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 48
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

based on a controlled dictionary (e.g., Quality control testing -

Biological , Quality control testing Chemical/Physical,....)

search Criteria for Manufacturing Activity

2.5.2 Manufacturer(s) of the medicinal product and site(s)

of manufacture:

(Note: including manufacturing sites of any diluents / solvent pre-

sented in a separate container but forming part of the medicinal
product, quality control/ in-process testing sites, immediate and
outer packaging and importer(s). For each site provide the relevant
information.)

Sites mentioned in sections 2.5.1 and 2.5.1.2 should only be re-

peated here when they have an additional function in the manufac-
turing of the medicinal product.

A brief description of functions performed for each manufacturer(s)

concerned is available in the dropdown field based on a controlled
dictionary (e.g., Primary packaging, quality control testing, Process-
ing of medicinal product, etc.)

The term “Processing of medicinal product” covers the manufacture

of the finished product. “This terminology is based on the agreed
terms used in the EU format for MIAs and GMP certificates included
in the Compilation of Community Procedures on Inspections and
Exchange of Information.

Note. More information about the functions performed is available

at http://eutct.ema.europa.eu/eutct
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 49
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

2.5.3 Manufacturer(s) of the active substance(s) and site(s)

of manufacture

Note: All manufacturing sites involved the manufacturing process of

each source of active substance, including quality control/ in-pro-
cess testing sites, should be listed. Broker or supplier details alone
are not acceptable. For biotech products include all sites of storage
of master and working cell bank and preparation of working cell
banks when relevant.

For each site provide the relevant information.

The values for Active Substance are populated from “Declaration

and Signature section” (please refer to the administrative data in
the user guide).

A brief description of manufacturing steps performed by manufac-

turing site for each manufacturer(s) concerned is available in the
dropdown field based on a controlled dictionary (e.g., Manufacture
of active substance, Manufacture of active substance intermediate,
Packaging of active substance, .etc)

Note. More information about the manufacturing steps performed is

available on http://eutct.ema.europa.eu/eutct

Note: When other procedures selected in Section 1– both free text

field and drop down field will be visible and either one is mandatory

Several items are included on the e-Application Form and should be

selected based on the following criteria:
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 50
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

• item # 1: GMP inspection evidence from EEA or state

with MrA etc.

Indicate if the site has been inspected for GMP compliance by an

EEA authority or by an authority of countries where MRA or other
European Union arrangements apply within the terms of agreement

In case of YES provide the EU-GMP Certificate reference number

or attach latest GMP certificate.

• item # 2: other GMP inspection evidence

In case of YES provide summary information in Annex 5.9.

• item # 3: CEP

Indicate if a Ph. Eur. Certificate of suitability has been issued for

the active substance(s):

In case of YES provide the Name of the CEP holder, the Name
of all manufacturers if different from the above, the CEP number
and the date of the last update. Provide copy of certificate in
Annex 5.10.

• item # 4: AsMF

Indicate if an Active Substance Master File has been used for the
active substance(s)

In case of YES, complete the information required and attach

letter of access for European Union/Member State authorities
where the application is submitted (see “European ASMF proce-
dure for active ingredients”) (Annex 5.10)
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 51
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

In case of modification of the manufacturing process or speci-

fications according to Annex 1 of Directive 2001/83/EC attach
copy of confirmation from the manufacturer of the active sub-
stance to inform the applicant

• item # 5 VAMF

Indicate if an EMA certificate for a Vaccine Antigen Master File

(VAMF) has been issued or submitted in accordance with Di-
rective 2001/83/EC Annex I, Part III. In case of YES complete
the information required and provide a copy of the certificate in
Annex 5.9.

2.5.4 Contract companies used for clinical trial(s) on bio-

availability or bioequivalence or used for the validation of
blood product manufacturing processes. For each contract
company state where analytical tests are performed and
where clinical data are collected

This section is not restricted only to generic applications.

Duty performed according to contract: A brief description of the

duty performed according to the contract should be given.

For each contract company, clearly indicate where analytical tests

are performed and where clinical data are collected. The subsec-
tions should be repeated, if necessary.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 52
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

2.6 qualitative and quantitative composition

2.6.1 qualitative and quantitative composition in terms of

the active substance(s) and the excipient(s)

The Qualitative and quantitative composition in terms of the ac-

tive substance(s) and the excipient(s) should be consistent with the
composition presented in Module 3.2.P.1

The presentation of the composition should take account of the rec-

ommendations of the QRD Recommendations on the expression of
strength in the name of centrally authorised human medicinal prod-
ucts (as stated in section 1 of SmPC, and in the name section of
labelling and PL) [EMA/707229/2009], http://www.ema.europa.eu/
docs/en_GB/document_library/Regulatory_and_procedural_guide-
line/2010/01/ WC500056428.pdf

In some cases an interval of values could be indicated in “Quan-

tity/Unit” fields, for example, in the case of radiopharmaceutical
products, or for some excipients used “q.s.p.” for a pH. Under “ref-
erence/monograph standard” the current Ph.Eur reference should
be indicated. Where no Ph Eur monograph exists, reference to a
monograph of a national pharmacopeia, an in-house monograph,
or monograph of a third country pharmacopeia can be included.

2.6.2 list of materials of animal and/or human origin con-

tained or used in the manufacturing process of the medic-
inal product?
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 53
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

MarKeting autHorisation aPPlication Particulars

If a substance is listed, it should be clear that if no Certificate of

suitability for TSE is available, appropriate data should be included
in relevant sections of the dossier (3.2.A.2, 3.2.S.2.3 or 3.2.P.4.5).

2.6.3 is an EMA certificate for a Plasma Master File (PMF)

issued or submitted in accordance with directive 2001/83/
EC Annex i, Part iii, being used for this MAA?

2.6.4 does the medicinal product contain or consist of Genet-

ically Modified Organisms (GMOs) within the meaning of
directive 2001/18/EC?
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 54
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

scientiFic aDVice

3. sCiEnTiFiC AdViCE

3.1 Was there formal scientific advice(s) given by EMA for this
medicinal product? Was there scientific advice(s) given by
Member state(s) for this medicinal product?

These sections may be replicated when needed.

CEP en Registro de Medicamentos y Regulatory Affairs
pag. 55
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

otHer MarKeting autHorisation aPPlications

4. OTHEr MArKETinG AUTHOrisATiOn APPliCATiOns

4.1 For national / MrP / dCP applications, please complete

the following in accordance with Article 8(j)-(l) of directive
2001/83/EC

4.1.1 is there another Member state(s) where an applica-

tion for the same* product is pending**?

If yes, section 4.2 must be completed.

4.1.2 is there another Member state(s) where an authori-

sation is granted for the same product?

Where differences are identified by the applicant concerning au-

thorisations granted in other Member States through a national
procedure /MRP/ DCP, the applicant should explain clearly if dif-
ferent therapeutic indications have been granted in those Member
States and on which grounds.

4.1.3 is there another Member state(s) where an authori-

sation was refused/suspended/ revoked by competent au-
thorities for the same product?

If yes, section 4.2 must be completed.

* “same product” means same qualitative and quantitative

composition in active substance(s) and having the same
pharmaceutical form from applicants belonging to the
same mother company or group of companies Or which
are “licensees”
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 56
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

otHer MarKeting autHorisation aPPlications

** This is covering applications submitted at an earlier time

or in parallel to this application if not already listed under
1.1.2 or 1.1.3

4.2 Marketing authorisation applications for the same product

in the EEA

(Same qualitative and quantitative composition in active substance(s) and

having the same pharmaceutical form from Applicants belonging to the
same mother company or group of companies or which are “Licensees”).

Note: refer to Commission Communication 98/C229/03

For each case (authorised, pending, refused, withdrawn, suspended or

revoked), all the information should be linked to one country and the
whole section could be duplicated. This whole section 4.2 should be up-
dated by the applicant as soon as a change occurs during the procedure.

In case of refusal, withdrawal by the Applicant, suspension or revocation

by a Competent Authority, the reason for refusal, withdrawal, suspen-
sion or revocation should be clearly specified.

4.3 For multiple / duplicate applications of the same medicinal

product

Multiple / duplicate applications (submitted simultaneously or subse-

quently to the original product) for: All the information should be linked
to one duplicate and the whole section should be replicated for each
duplicate application.

A copy of letter from Commission services is required for validation in

the centralised procedure.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 57
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

otHer MarKeting autHorisation aPPlications

Moreover, in case of parallel multiple applications, the applicant is re-

quested to use the same legal basis as for the original authorisation
application.

4.4 Marketing authorisation applications for the same product

outside the EEA

(i.e. from applicants belonging to the same mother company or group of

companies or which are “licensees”. Same qualitative and quantitative com-
position in active substance(s) and having the same pharmaceutical form.)

Note: refer to Commission Communication 98/C229/03

For each case (authorised, pending, refused, withdrawn, suspended or

revoked) all the information should be linked to one country and the
whole section could be duplicated. In case of refusal, withdrawal, suspen-
sion or revocation, the reason for each case should be clearly specified.
CEP en Registro de Medicamentos y Regulatory Affairs
pag. 58
TEMA 2.1: PrEPArACión dEl E-AF

3. sECCiOnEs y qUE COnTEnidO dEl E-AF

ANNEXED DOCUMENTS (where appropriate)

5. AnnEXEd dOCUMEnTs (where appropriate)

All annexes provided should be identified by the correct identification

number.