Common Baltic Package: What and When it applicable?

Estonia, Latvia and Lithuania are accepting Common Baltic Package. This is a voluntary procedure applicable to changes of the labeling referred to in the Article 61(3) of the Directive 2001/83/EC.

In order to have common Baltic labelling, Marketing Authorisation holders (MAH's) will never need to discuss it with each agency separately. During this procedure, MAH’s will communicate with only one agency (Reference Baltic State) acting on behalf of all three instead. An e-mail application with accompanying documents will be sufficient. The procedure will somehow resemble DCP.

Procedures will be coordinated by Estonian Agency of Medicines. Contact points are the following:

• EE:      labelling@ravimiamet.ee
• LV:      baltic_labelling@zva.gov.lv
• LT:      baltic_labelling@vvkt.lt

Prerequisites:

• Summary of Product Characteristics does not contain any differences that preclude harmonization of the labeling.
• Name of the medicinal product is the same in all Baltic States.
• Labeling shall comply with relevant EU/EMA/QRD.
• There is no ongoing variation procedure that could affect labeling
• There is no renewal procedure ongoing

Reference: The Common Baltic Package Procedure

EMA good pharmacovigilance practice modules for public consultation

EMA releases good pharmacovigilance practice modules for public consultation

The EMA has released the first batch of modules on Good Pharmacovigilance Practices (GVP) for public consultation until 18 april 2012.  

GVP is a set of measures drawn up to facilitate the performance of Pharmacovigilance in the European Union. They apply to marketing-authorization holders, the Agency and medicines regulatory authorities in EU member states and aim to improve safety for patients by strengthening  Pharmacovigilance  across the EU. They cover medicines authorized centrally via the agency as well as medicines authorized at the national level.  

GVP covers following aspects of safety monitoring of medicines. These are:

Module I: Pharmacovigilance systems and their quality systems

Module II: Pharmacovigilance systems master files

Module V: Risk management systems

Module VI: Management and reporting of adverse reactions to medicinal products

Module VII: Periodic safety update reports

Module VIII: Post-authorization safety studies

Module IX: Signal management

The release of these modules is a key deliverable of the 2010 Pharmacovigilance legislation, which will apply from july 2012. Each module was developed by a team consisting of experts from the agency and from EU member states.

The Agency is seeking comments on the practical implementation of the legislation as outlined int these modules. The underlying legal requirements cannot be altered through this consultation process.

Agency intends to finalize and publish these modules by July 2012, after comments from stakeholders have been taken into account.

Reference: EMA releases good pharmacovigilance practice modules for public consultation

PUMA

PUMA - Pediatric Use Marketing Authorization 

According to Article 30 of Regulation (EC) No 1901/2006 - The Paediatric Regulation, the paediatric use marketing authorisation (PUMA) is a dedicated marketing authorisation for medicinal products indicated exclusively for use in the paediatric population. It has been designed to promote paediatric development of already authorised products which are no longer covered by a supplementary protection certificate (SPC) or a patent qualifying for a SPC.

Incentives:

• 8+2 year period of data and market protection
• Partial exemption from the payment of fees
• ‘Automatic access’ to the centralised procedure
• A medicinal product for which a PUMA has been granted may retain the name of another medicinal product containing the same active substance for which the same holder has been granted an authorisation for use in adults

Required Documentation:

• Combination of new data and/or existing data
• Depending on the legal basis of the application, submission of literature and/or cross-reference to the dossier of another medicinal product may be used.
• A PUMA application has to contain the results of all studies performed and details of all information collected in compliance with an agreed Paediatric Investigation Plan (PIP). 
• PDCO opinion on compliance or the applicant’s compliance report must be provided in Module 1.10
• Risk management plan

Reference:

1. Regulation (EC) No 1901/2006 
2. Special Topics - Medicines for children - PUMA

How to calculate Patent expiry & Exclusivity in EU

A generic medicine can only be marketed once the patents and the supplementary protection certificates (SPCs) covering the originator product have expired. Data exclusivity also limits the time when a generic manufacturer can make an application for a marketing authorisation based on demonstrating bioequivalence with the originator product. 

Patents: Patents are used to protect a product, process, apparatus or use that has a practical purpose. Registration provides a patentee the right to prevent anyone making, using, selling, or importing the invention for 20 years. Any given pharmaceutical product is typically protected by  

20-40 different patents on various aspects and properties of the product. The pharmaceutical properties eligible for patenting is different from country to country.

Pharmaceutical properties eligible for patenting in EU:

• Primary uses
• Processes and intermediates
• Bulk forms
• Simple formulations
• Composition of matter
• Expansive numbers of uses
• Methods of treatment
• Mechanism of action
• Packaging
• Delivery profiles
• Dosing regimen
• Dosing range
• Dosing route
• Combinations
• Screening methods
• Chemistry methods
• Biological target
• Field of use

To get patent expiry date, add 20 years to application date shown on front page of patent.

SPC (Supplementary Protection Certificate): It is a unique intellectual property (IP) right that provides an additional monopoly that comes into force after expiry of a patent upon which its based.The purpose of the supplementary protection certificate for medicinal products is to remedy the disparities and shortcomings in national patenting systems for pharmaceutical research. It aims in particular to guarantee sufficient protection for the development of medicinal products in the European Union (EU).

Criteria to get SPC:

• The product is protected by a basic patent in force;
• The product, as a medicinal product, has been granted a marketing authorisation;
• The product has not already been the subject of a certificate;
• The marketing authorisation is the first authorisation to place the product on the market as a medicinal product.

The certificate cannot be granted for a period exceeding five years. Furthermore, the duration of protection afforded by a patent and by the certificate cannot exceed 15 years overall for the holder's first marketing authorisation.

Exclusivity:  An application for approval of a New Chemical Entity must contain data to allow assessment of the safety and efficacy profile. These data include pharmacological and toxicological tests and the results of clinical trials.

To avoid repeating such tests and trials, applications for generic pharmaceutical substances are not required to include these data; instead they may rely on the data provided in relation to the NCE application. However, EC directive 2001/83/EC prevents regulatory authorities from accepting applications for approval of generics that rely on this data until a data exclusivity period has expired.

This period starts on the day of the first marketing authorisation in the European Community, and expires either six or ten years thereafter, depending on the country in which the application is to be filed and the procedure used to file it.

Data exclusivity relates to the active ingredient per se, new periods of data exclusivity are not applied to later approval of new dosage forms, routes of administration or indications.

Two types of provisions are there in EU for Regulatory Data Protection:

• 6/10 years Old provision
• 8+2+1 years New provision

6/10 years Old provision: This provision is applicable to medicinal products (Reference products) application was submitted before 31 October 2005.

10 Years for national authorisations granted by: Belgium, Germany, France, Italy, the Netherlands, Sweden, United Kingdom, Luxemburg.

6 years for national authorisations granted by: Austria, Denmark, Finland, Ireland, Portugal, Spain, Greece, Poland, Czech Republic, Hungary, Lithuania, Latvia, Slovenia, Slovakia, Malta, Estonia, Cyprus and also Norway, Liechtenstein and Iceland.

10 years for all medicinal products authorised through the centralised procedure.

• To calculate the expiry of the data exclusivity period for centralised applications add 10 years to the corresponding European First Marketing Authorisation Date.
• To calculate the expiry of the data exclusivity period for national or mutual recognition procedure applications, add (6 years or 10 years depends on country) to the corresponding European First Marketing Authorisation Date.

8+2+1 years New provision: The 2001/83/EC Directive introduces a harmonized "8+2+1" formula for new drugs approved either through the centralized procedure or the mutual recognition procedure.

This provision is applicable to medicinal products (Reference products) application was submitted after 31 October 2005.

• 10 (8+2) years market exclusivity

• 8 years data protection

• 2 years for generic companies to prepare, apply 
  for and receive a MA. The generic MAH is not 
  allowed to place his product on the market until 10 
  years have expired

• +1 year: During the first eight years of those ten years, the MAH obtains an authorisation for one or more new therapeutic indications which, during the scientific evaluation prior to their authorisation, are held to bring a significant clinical benefit in comparison with existing therapies.

To get data exclusivity expiry date: Add 10 years to the corresponding European First Marketing Authorisation Date, plus another 1 year if a new indication has been approved. To calculate the earliest date for filing a generic application, add 8 years to the corresponding European First Marketing Authorisation Date. 

How to Design the Regulatory Strategy for Generic Application in EU

Regulatory strategy: Regulatory strategy could be seen as the adaptations a company makes to move its product from the development state to achieving marketing approval. It incorporates the drug development plan, an outstanding issue or question, background information, regulations and/or guidance documents, strategic advice and recommendations on implementation.

Example - Strategy for Generic Application in EU

Drug: Brimonidine Tartrate 0.2% w/v (2 mg/ml) Eye Drops


Dosage form: Eye drops


Date of marketing authorization: 1997-03-18


MA Holder: Allergan Ltd.


Innovator: Alphagan®,0.2% w/v (2mg/ml) eye drops


Question: What would be the legal basis for my application?

Summary

Background and Definitions


Article 8(3) of Directive 2001/83/EC: Provides the information on full application so applicable to new drugs 


Article 10 - Generic, hybrid or similar biological applications:

a. Generic applications: According to Article 10(1) of Directive 2001/83/EC, the applicant is not required to provide the results of pre-clinical tests and clinical trials if he can demonstrate that the medicinal product is a generic medicinal product of a reference medicinal product which is or has been authorised under Article 6 of Directive 2001/83/EC for not less than 8 years in a Member State or in the Community.

A generic medicinal product is defined as a medicinal product that has:

• Same qualitative and quantitative composition in active substances as the reference product,
• same pharmaceutical form as the reference medicinal product,
• Whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies.

b. Hybrid applications: Hybrid applications under Article 10(3) of Directive 2001/83/EC differ from generic applications in that the results of appropriate pre-clinical tests and clinical trials will be necessary in the following three circumstances:

• strict definition of a ‘generic medicinal product’ is not met;
• bioavailability studies cannot be used to demonstrate bioequivalence;
• changes in the active substance(s), therapeutic indications, strength, pharmaceutical form or
• route of administration of the generic product compared to the reference medicinal product

c. Similar biological application: In Article 10(4) of Directive 2001/83/EC

Article 10a - Well-established use application

Article 10b - Fixed combination application

Article 10c - Informed consent application

Assumptions:Put in assumption about hybrid application Article 10(3) of Directive 2001/83/EC (Because eye drops - bioavailability studies cannot be used to demonstrate bioequivalence)

Strategic advice: As per the note for guidance on the clinical requirements for locally applied, locally acting products containing constituents (CPMP/EWP/239/5) defines the clinical requirements for locally acting products with a known active substance.

Locally acting products are products which are applied locally and are assumed to exert their effect at the site of the application.

Examples are dermatological products (e.g. creams, ointments), inhalatory products like powders or aerosols for inhalation, eye drops, ear drops, nasal products, but also other products which act locally.

It is necessary to show for locally acting products that the product to be approved (either a generic or reformulated product) is therapeutically equivalent to the product already approved (based on a full dossier).

What would be the route of procedure?

a. centralized procedure: If SmPC is harmonized in all countries, applicant can choose centralized procedure.

b. Mutual Recognized procedure (MRP): If the product is already registered in a member state. The MRP starts with a National procedure with the chosen RMS. To run a MRP you need at least a RMS and one CMS. The amount of CMSs can be as big as 26. In an ideal world the MRP will take 420 days: 210 days for the National Procedure (license granted by the RMS) + 90 days for the assessment report from the RMS + 90 days for the MRP + 30 days for the national steps (translation of the SmPC, packaging materials and providing the license). The Marketing Authorization is issued by the national agency. The MRP can be repeated if you want to add additional member states at later dates - this is called repeat MRP second wave and so on. The RMS remains the same and the member states where the product was already registered through the MRP remain involved.

c. Decentralized procedure (DCP): If the product is not registered yet in any member state. You need at least RMS and one CMS. The procedure starts without a National Procedure. The dossier will be submitted to all the involved Member States at the same time. It is possible to end the procedure at Day 105 if consensus is reached, at Day 120, at Day 150 and at Day 210 (followed in each case by 30 days for the national steps). The assessment report will be send from the RMS to the involved CMS at Day 70. The standard clock stop is 90 days. The Marketing Authorization is issued by the national agency.

d. National procedure: If the product is not registered in any member state and if the application is restricted to one member state. The official time for granting a license is 210 days (without the clock stop) but in real life the average is about one year. The MA is then issued by the national agency.

Criteria for selecting a RMS

• Size of market within the EU
• Patents/Data Exclusivity & Market Exclusivity
• Registration cost (Strength specific)
• Consideration of future variations
• Potential for specific up-front agreements
• Long-term partnership
• Reference product availability
• Availability of slots (For DCP)

Date of first marketing authorization is 1997-03-18, so while selecting RMS and CMS Data

exclusivity has to consider as the important factor. Because data exclusivity is differs from county to country if the date of marketing authorization is before 31 October 2005.

10 years: Belgium, Germany, France, Italy, the Netherlands, Sweden, United Kingdom,

Luxemburg;

6 years: Austria, Denmark, Finland, Ireland, Portugal, Spain, Greece, Poland, Czech Republic, Hungary, Lithuania, Latvia, Slovenia, Slovakia, Malta, Estonia, Cyprus and also Norway, Liechtenstein and Iceland.

The “8+2 +1” formula applies to all new medicinal products where the application was submitted after 31 October 2005. In these cases generic medicines companies can apply for a marketing authorisation based on bioequivalence only after the 8-year data exclusivity period has expired, and can only market their products two or three years after that. The effective period of marketing exclusivity is therefore 10 or 11 years. The extra year applies when new indications (which have significant clinical benefit) are added by the originator during the first eight years of marketing the product.

Two options:

1. If DCP slots are available better to go for DCP, because applicant can get MA in more countries with single filling.

2. If Applicant having potential for specific up-front agreements with local parties better to go for national procedure, because applicant can get MA in short period of time, later can extend to Remaining countries through MRP.

References:

1. Council Directive 2001/83/EC

2. Council Directive 2004/27/EC

3. The Notice to Applicants Volume 2A Procedures for marketing authorization

Fundamentals of EU Drug Regulatory Affairs

The history of pharmaceutical legislation in the European Union (EU) is intricately linked with legislation and harmonisation across other socioeconomic sectors as well as ever-increasing membership of the EU. The unique strength of the European system of licensing and monitoring medicinal products lies in the scrutiny a new drug, or the safety of an approved drug, receives from the national authorities of all its Member States. A major advantage of this pan- European system is that it can draw on the expertise of all its Member States and, invariably, each application is closely scrutinised by all the experts and advisory committees of each of its Member States. The EU system, through initiatives of its Member States, has provided important leads to other regulatory authorities of the world, either indirectly or formally through the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).

The websites of the EU and the European Medicines Agency (EMEA) include all legislation and guidelines as well as a vast amount of information related to pharmaceutical procedures and medicinal products.

I. Member states: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovak Rep., Slovenia, Spain, Sweden, United Kingdom.

II. Regulatory Agencies and Pharmaceutical Organizations in EU:

1. EMA: The European Medicines Agency (EMA) is a decentralized body of the European Union, located in London. The Agency is responsible for the scientific evaluation of applications for European marketing authorizations for both human and veterinary medicines (centralized procedure).

Further information: European Medicines Agency
2. HMA: The Heads of Medicines Agencies is a network of the Heads of the National Competent Authorities whose organizations are responsible for the regulation of Medicinal Products (Mutual reorganization procedure and Decentralized procedure) for human and veterinary use in the European Economic Area.

Further information: Heads of Medicines Agencies
3. EGA: The EGA is the official representative body of the European generic and biosimilar pharmaceutical industry, which is at the forefront of providing high-quality affordable medicines to millions of Europeans and stimulating competitiveness and innovation in the pharmaceutical sector.

Further Information: European Generic Medicine Association
4. Eudralex: "The rules governing medicinal products in the European Union" called as Eudralex. It consists 10 volumes; each volume describes each pharmaceutical activity.

a. Concerning Medicinal Products for Human use:

Volume 1 - Pharmaceutical Legislation.

Volume 2 - Notice to Applicants.

Volume 2A deals with procedures for marketing authorisation.

Volume 2B deals with the presentation and content of the application dossier.

Volume 2C deals with Guidelines.

Volume 3 - Guidelines.

b. Concerning Medicinal Products for human use in clinical trials (investigational medicinal products):

Volume 10 - Clinical trials.

c. Concerning Veterinary Medicinal Products:

Volume 5 - Pharmaceutical Legislation.

Volume 6 - Notice to Applicants.

Volume 7 - Guidelines.

Volume 8 - Maximum residue limits.

d. Concerning Medicinal Products for Human and Veterinary use:

 Volume 4 - Good Manufacturing Practices.

Volume 9 - Pharmacovigilance.

e. Miscellaneous:

Guidelines on Good Distribution Practice of Medicinal Products for Human Use (94/C 63/03)

Further information: Eudralex

5. National Competent Agencies

Further information: EU Members states Agencies
III. European pharmaceutical legislation: The EU has a set of legal instruments known as either the Regulations or the Directives. In addition, the European Commission (EC) issues communications to clarify its legal understanding of the legislation or requirements. There are also guidelines issued by various EU regulatory bodies. Legislation is two types:

1. Legally binding acts

a) Regulation: A regulation is an act of general application, binding in its entirety and directly applicable in all Member States. It does not require any transposition by the national authorities.

Ex: Commission Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products

b) Directive: A Directive is a legal instrument that is binding, as to the result to be achieved, upon each Member State to whom it is addressed. However, the national authorities are left the choice of form and methods to achieve their objectives. Directives may be addressed to individual, several or all Member States. In order to ensure that the objectives laid down in Directives become applicable to individual citizens, an act of transposition by national legislators is required, whereby national law is adapted to the objectives laid down in Directives.

Ex: Directive 2001/83/EC relating to medicinal products for human use

c) Decision: A decision is a legal act binding in its entirety upon those to who it is addressed (Member State or natural or legal person).

Ex: Council Decision 1999/468/EC with regard to the regulatory procedure with scrutiny Adaptation to the regulatory procedure with scrutiny

2. Soft law

a) Resolution: A resolution is a declaratory act not provided for by the EC Treaty that is published by the Council and the European Parliament in order to inform of their positions on a specific subject, and, where necessary, that invites the Commission to propose the appropriate measures.

A resolution is rather a political than a legal act, it does not create a legal obligation.

Ex: Council Resolution on a global approach to conformity assessment

b) Communication: A Communication is an act not provided for by the EC Treaty, which is without binding legal effect.

It indicates to governments and economic actors how the Commission is planning to apply or wishes to see applied a given Community rule.

The Court of Justice of the European Communities often supports its interpretation of legally binding acts with Commission communications.

Ex: Communication from the Commission - Guideline on the format and content of applications for agreement or modification of a paediatric investigation plan and requests for waivers or deferrals and concerning the operation of the compliance check and on criteria for assessing significant studies

c) Guidelines

Community guidelines (EMA – Applicable to total Member states)

Guidelines are texts covering technical topics, their legal status may differ:

- Guidelines resulting from a formal request laid down in a Community Directive or Regulation are binding when those acts so provide, and must be complied with when the corresponding Directive or Regulation is implemented.

The Commission publishes them, e.g. the “Note for Guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products”.

National guidelines (Applicable to single member state only).

Ex: Netherlands (MEB): Duplex marketing authorization

Ireland (IMB): Human medicines gudiance

d) Notice to applicants

The Commission publishes this guidance in “The rules governing medicinal products in the European Union”. Popularly known as EudraLex.

IV. Types of procedures: There are currently four different procedures that can be used to submit a medicinal product for marketing approval in the European Union.

• Centralized Procedure (CP)
• Mutual Recognition Procedure (MRP)
• Decentralized Procedure (DCP)
• National procedure

V. Types of applications: As per directive 2001/83/EC, following types of applications are available for registration of pharmaceuticals.

• Full application
• Generic application
• Hybrid application
• Similar biological application
• Well-established use application
• Fixed combination application
• Informed consent application

VI. Variations:
Variations are by definition any amendment (i.e. addition/deletion/changing the content) to the documentation representing the legal basis for each Marketing Authorisation (MA) of a medicinal product. Variations classifed as Type I (A & B) and Type II. EU variation regulation has been revised and main changes are:

• Introduction of a European annual reporting system (do and tell procedure)
• Possibility for grouping of variations
• Reduction of duplicate work by using a worksharing procedure
• Implementation of design space concept according ICH.
• Type IB by default for previously not defined variations and safeguard clause

Further information: Variation guidelines

Types of Applications for Registration of Pharmaceuticals in EU

As per Directive 2001/83/EC, following types of applications are available for Registration of Pharmaceuticals.

1. Full application 
2. Generic application
3. Hybrid application
4. Similar biological application 
5. Well-established use application 
6. Fixed combination application 
7. Informed consent application

1. Full application: Article 8(3) of Directive 2001/83/EC deals the required information for full application. Applicant has to submit the the results of pharmaceutical tests (physico-chemical, biological or microbiological), pre-clinical tests (pharmacological and toxicological), and clinical trials need to be submitted.

Detailed data requirements are set-out in Annex I to Directive 2001/83/EC, as amended by Directive 2003/63/EC.

Where Module 4 and/or 5 consists of a combination of reports of limited non-clinical and/or clinical studies carried out by the applicant and of bibliographical references this kind of application has also to be submitted according to Article 8(3) of Directive 2001/83/EC (So-called ‘full-mixed’ application)

2.Generic application: According to Article 10(1) of Directive 2001/83/EC, the applicant is not required to provide the results of pre-clinical tests and clinical trials if he can demonstrate that the medicinal product is a generic medicinal product of a reference medicinal product which is or has been authorized for not less than 8 years in a Member State or in the Community.

A generic medicinal product is defined as a medicinal product that has:

• The same qualitative and quantitative composition in active substances as the reference product,

• The same pharmaceutical form as the reference medicinal product

• And whose bio-equivalence with the reference medicinal product has been demonstrated by appropriate bio-availability studies.

3. Hybrid application: Hybrid applications under Article 10(3) of Directive 2001/83/EC differ from generic applications in that the results of appropriate pre-clinical tests and clinical trials will be necessary in the following three circumstances:

• Where the strict definition of a ‘generic medicinal product’ is not met;

• Where the bioavailability studies cannot be used to demonstrate bioequivalence;

• Where there are changes in the active substance(s), therapeutic indications, strength, pharmaceutical form or route of administration of the generic product compared to the reference medicinal product

• These applications will thus rely in part on the results of pre-clinical tests and clinical trials for a reference product and in part on new data.

4.Similar biological application: In Article 10(4) of Directive 2001/83/EC it is stated that where a biological medicinal product which is similar to a reference biological product, does not meet the conditions in the definition of generic medicinal products, owing to, in particular, differences relating to raw materials or differences in manufacturing processes of the similar biological medicinal product and the reference biological medicinal product, the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided.

5. Well-established use application: According to Article 10a of Directive 2001/83/EC, as amended it is possible to replace results of preclinical and clinical trials by detailed references to published scientific literature (information available in the public domain) if it can be demonstrated that the active substances of a medicinal product have been in well-established medicinal use within the Community for at least 10 years, with recognized efficacy and an acceptable level of safety.

Criteria for well-established use:

• The time over which a substance has been used with regular application in patients; quantitative aspects of the use of the substance, taking into account the extent to which the substance has been used in practice, the extent of use on a geographical basis and the extent to which the use of the substance has been monitored by pharmacovigilance or other methods;
the degree of scientific interest in the use of the substance (reflected in the published scientific literature) and the coherence of scientific assessments

• Applicants should submit Modules 1, 2 and 3 as described in EU-CTD, For Modules 4 and 5, a detailed scientific bibliography shall address all required pre-clinical and clinical characteristics, and should be summarised in Module 2.

6.Fixed combination application: According to Article 10b of Directive 2001/83/EC, in the case of medicinal products containing active substances used in the composition of authorised medicinal products but not hitherto used in combination for therapeutic purposes, the results of new pre-clinical tests or new clinical trials relating to that combination shall be provided in accordance with Article 8(3)(i) of the same Directive, but it shall not be necessary to provide scientific references relating to each individual active substance.

The combination of active substances within a single pharmaceutical form of administration according to this provision is a so-called ‘fixed combination'

7. Informed consent application: According to Article 10c of Directive 2001/83/EC as amended, following the granting of a marketing authorization, the authorisation holder may allow use to be made of the pharmaceutical, non clinical and clinical documentation contained in the dossier of the medicinal product for the purpose of examining subsequent applications relating to other medicinal products possessing the same qualitative and quantitative composition in terms of active substances and the same pharmaceutical form.

Applicant has to submit the Module 1, including the Application Form with relevant Annexes and letter of consent from the MAH of the authorised medicinal product allowing access to modules 2, 3, 4, 5 of the initial dossier and any subsequent documentation submitted.

Reference:

1. Directive 2001/83/EC