Marketing Authorisation in Europe

Authorisation Procedures for medicinal products

Procedures for evaluating medicinal products and granting marketing authorisation

The European system for the authorisation of medicinal products for human and animal use was introduced in January 1995 with the objective of ensuring that safe, effective and high quality medicines could quickly be made available to citizens across the European Union.

The European system offers several routes for the authorisation of medicinal products:

• The centralised procedure, which is compulsory for products derived from biotechnology, for orphan medicinal products and for medicinal products for human use which contain an active substance authorised in the Community after 20 May 2004 (date of entry into force of Regulation (EC) No 726/2004) and which are intended for the treatment of AIDS, cancer, neurodegenerative disorders or diabetes. The centralised procedure is also mandatory for veterinary medicinal products intended primarily for use as performance enhancers in order to promote growth or to increase yields from treated animals.
  Applications for the centralised procedure are made directly to the European Medicines Agency (EMA) and lead to the granting of a European marketing authorisation by the Commission which is binding in all Member States.
• The mutual recognition procedure, which is applicable to the majority of conventional medicinal products, is based on the principle of recognition of an already existing national marketing authorisation by one or more Member States.
• The decentralised procedure, which was introduced with the legislative review of 2004, is also applicable to the majority of conventional medicinal products. Through this procedure an application for the marketing authorisation of a medicinal product is submitted simultaneously in several Member States, one of them being chosen as the "Reference Member State". At the end of the procedure national marketing authorisations are granted in the reference and in the concerned Member States.

Purely national authorisations are still available for medicinal products to be marketed in one Member State only.

Special rules exist for the authorisation of medicinal products for paediatric use, orphan drugs, traditional herbal medicinal products, vaccines and clinical trials.

The EMA and the authorisation procedure

In 1993 the European Medicines Agency (EMA) was founded with the primary task of providing scientific advice of the highest possible quality to the Community Institutions on all matters relating to medicinal products for human and veterinary use. EMA's main task is to co-ordinate the scientific evaluation of the safety, efficacy and quality of medicinal products which undergo either procedure. All scientific questions arising in these procedures are dealt with by the EMA.

The agency has today established itself as a world-leading agency for the evaluation of medicinal products. It constitutes a major asset in making Europe an attractive location for new pharmaceuticals and allows for speedy and robust authorisation of new innovative medicines.

EMA's key tasks are to:

• provide Member States and Community institutions with the best possible scientific advice on questions about the quality, safety and efficacy of medicinal products for human and veterinary use;
• establish a pool of multinational scientific expertise (by mobilising existing national resources) in order to achieve a single evaluation via the centralised or mutual recognition marketing authorisation procedures;
• organise speedy, transparent and efficient procedures for the authorisation, surveillance and where appropriate, withdrawal of medicinal products in the EU;
• advise companies on the conduct of pharmaceutical research;
• reinforce the supervision of existing medicinal products (by co-ordinating national pharmacovigilance and inspection activities);

• create databases and electronic communication facilities as necessary to promote the rational use of medicines.

What is a Marketing Authorisation needed for?

In accordance with EU Directive 2001/83 and Regulation (EC) No. 726/2004 governing medicinal products, in order to legally place a medicinal product on the market in the European Economic Area (EEA), a Marketing Authorisation (MA) or ‘licence’ must first be approved. To obtain an MA, a Marketing Authorisation Application (MAA) is submitted to the appropriate Competent Authority(s) (CAs), for assessment and MA approval.

What does an MAA consist of?

An MAA is a comprehensive dossier of information and data describing all aspects (Administrative/Quality/Safety/Efficacy) of a medicinal product demonstrating that it is appropriate for use in patients. There is an internationally agreed standard for the overall content and format for this dossier which is referred to as the Common Technical Document (CTD).

The CTD format is applicable for all MAA regulatory submission routes and all product types, although some modifications may be required for certain application/product types. CTD format is also applicable to other submission types including variations and renewals.

At the top level, a CTD dossier is split into five modules:

Module 1: Administrative information and prescribing information (any additional region-specific information not specified in the CTD is also included in this module)

Module 2: CTD Summaries

Module 3: Quality

Module 4: Non-clinical Study Reports

Module 5: Clinical Study Reports

The overall organisation of the CTD is fixed and should not be changed. Documents and data should be assigned to the most appropriate sections in Modules 1 to 5. The only exceptions to this are the non-clinical and clinical summaries, within which individual formats/tables can be modified as required to best present the data for assessment.

What information and data is required in each CTD Module?

Guidance on the top level structure and content of the CTD dossier can be found in Eudralex Volume 2B of EC Notice to Applicants “Presentation and format of the dossier – Common Technical Dossier”.

CTD does not specify the detailed content in terms of what studies and data are required. There are European Community guidelines regarding the quality, safety and efficacy of medicinal products which must be considered and accounted for in preparation of the MAA dossier. In addition, for medicinal product quality, the general chapters and monographs of the European Pharmacopoeia or other national pharmacopoeias should also be accounted for as appropriate.

Not all data requirements are mandatory or required for each and every application or product type. If an element is considered to be not relevant or not applicable, the absence of such should be fully justified.

There may also be regional differences that will need to be taken into account in dossier preparation.

The following is a summarised description of the information to be included in each Module.

Module 1

This Module includes all of the administrative information relating to the application and the concerned medicinal product. Key items for inclusion are:

• Cover letter
• Application form and annexes (e.g. manufacturing licences, proof of payment of fees, letters of access)
• Product Information including the Summary of Product Characteristics (SmPC), labelling, patient leaflet, braille, results of readability testing
• Information about the experts
• Specific requirements for different types of applications
• Environmental Risk Assessment
• Pharmacovigilance system description
• Risk Management Plan

Module 2

This Module presents summary information for the quality, non-clinical and clinical Modules with so-called expert review of the information and data in the context of the MAA and regulatory framework.

Module 3

Module 3 is the Quality Module which presents all of the information regarding drug substance and drug product development, characterisation, manufacturing and testing to demonstrate that the medicinal product is of suitable quality.

Module 4

This is the Non-clinical Module which includes all of the non-clinical study reports and literature addressing the complete battery of non-clinical testing required for the medicinal product and application type.

Module 5

This is the Clinical Module which includes all of the clinical study reports and literature addressing the clinical requirements for the medicinal product and application type

Are there specified requirements for formatting such as filenames, margins, font type and size, hyperlinking, etc?

There is some general but limited guidance on formatting available, however the aim is obviously to facilitate dossier navigation and review. Margins need to be large enough to ensure that bindings do not obscure any data. The selected font and font size should be easily legible. Times New Roman and 12-point font are recommended for narrative text, although variations to this are accepted, for example for tabulated data where it might be necessary to reduce the font size slightly to ensure a table fits on the page.

In terms of pagination and segregation, documentation should be prepared in line withCHMP/ICH/2887/99 Revision 1 Organisation CTD recommendation.

National-only submissions must consider any Member State-specific requirements. For example in the UK, the MHRA recommends file naming conventions through Special Mail 5. European submissions would be in accordance with Non-eCTD electronic Submissions (NeeS) or fully electronic (eCTD) format.

Is there a requirement to re-format old dossiers?

There is no obligation to reformat approved dossiers. However it is possible to re-format Quality documentation into Module 3 format in order to facilitate ongoing life-cycle management of the licence, as variations, renewals, etc., will need to be submitted in CTD format. Re-formatting is not recommended for Modules 4 and 5 for Non-clinical and Clinical data.

When re-formatting into Module 3, all approved variations must be fully integrated into the re-formatted Module. In terms of the regulatory procedure to be followed to submit the re-formatted Module 3, this does not constitute a variation in itself. Therefore it is recommended that it is submitted as part of another regulatory procedure (e.g. variation or licence renewal), subject to agreement from the concerned CA.

If however, an old format licence is to be used as the basis for MAAs to be submitted via the Mutual Recognition Procedure (MRP), the current approved documentation will need to be reformatted intoCTD format. It is recommended that Applicants discuss any MRP plans with the proposed Reference Member State (RMS) in advance to determine the best means of doing this, as different Member States may prefer different approaches.

Are there different National administrative requirements (i.e. delivery addresses, number of copies, paper/electronic, etc)?

There are likely to be a variety of Member State-specific administrative requirements, some of which are documented in the available EU Guidances. However, there is still the possibility of additional requirements or nuances not readily available in the standard sources of information. In the absence of direct, recent experience of an MAA submission to the concerned Member States (MSs), it is highly recommended that contact be made with the relevant CA to establish any specific national requirements in advance of submission.

Requirements for final submission to the MSs again may vary and therefore needs to be checked in advance. In terms of final publication and dispatch of the MAA, this aspect of MAA preparation is often dismissed as minor, yet it requires the same level of care and attention as preparation of the dossier itself. Timelines frequently do not allow much time for this part of the project. Consequently any delays ahead of publication can mean publication and dispatch activities need to be completed at speed, potentially compromising the quality of the final submission.

What are the different types of MAA procedures?

Medicinal products can only be placed on the European Economic Area (EEA) market when a Marketing Authorisation has been issued by the competent authority of a Member State for its own territory (National Procedure) or when an authorisation has been granted in accordance with a community authorisation (Centralised Procedure (CP), Mutual Recognition Procedure (MRP) and Decentralised Procedure (DCP)).

National Procedure

The competent authorities of the Member States (MS) are responsible for granting MAs for products which are placed on their markets, except for medicinal products which are authorised under DCP,MRP and CP. In order to obtain a national MA, a single application is submitted to the competent authority of the MS.

Mutual Recognition Procedure

The Mutual Recognition Procedure aims at facilitating access to a single market by relying upon the principle of mutual recognition. A marketing authorisation or the assessment in one MS (the Reference Member State (RMS)) will in principle be recognised by the competent authorities of the other MSs (the Concerned Member States (CMS)), unless there are grounds for supposing that the authorisation of the medicinal product concerned may present a potential serious risk to public health.

After the first marketing authorisation is granted in one of the EU Member States, the MA Holder (MAH) may request one or more Member State(s) to recognise an authorisation granted by the RMSby submitting a MR application.

The Mutual Recognition Procedure is divided into the following steps:

Decentralised Procedure

The Decentralised Procedure is to be used in order to obtain marketing authorisations in several Member States where the medicinal product in question has not yet received a MA in any Member State at the time of application.

The Decentralised Procedure is divided into the following steps:

Centralised Procedure

Marketing Authorisation Applications for products that fall under the ‘mandatory’ or ‘optional’ scope of the Centralised Procedure, facilitate simultaneous approval in all EU Member States (including Iceland, Liechtenstein and Norway). The European Medicines Agency (EMA) will act as the Competent Authority for CP submissions.

Mandatory Scope – the Centralised Procedure is ‘mandatory’ for human medicines that are:

• Derived from biotechnology processes, such as genetic engineering
• Intended for the treatment of HIV/AIDs, cancer, diabetes, neurodegenerative disorders or autoimmune diseases and other immune dysfunctions
• Orphan medicinal products

Optional Scope – medicinal products can be accepted for consideration under the ‘optional’ route by the EMA, on the basis that the product contains either a new active substance or constitutes a significant therapeutic, scientific or technical innovation, or the authorisation is in the interests of patients within the community.

What are the differences between the MA procedures?

Centralised Procedure	Decentralised and Mutual Recognition Procedures	National Procedure
Less flexible procedure as only one tradename and one MA holder can be used	More flexible procedure as different tradenames and MA holders can be used	One tradename and oneMAH
The EMA chooses the Rapporteur / Co-Rapporteur for the assessment	The applicant chooses theRMS with the most relevant expertise	The applicant chooses the country
All or nothing procedure as the MAA is either accepted or rejected in all EU Member States	Can withdraw MAA from Member States that are causing difficulties, whilst continuing with applications in other states	Can withdraw the MAA at anytime
One application and one assessment	Multiple assessments and complex administration procedures	One application and one assessment
Well defined timescale throughout the procedure	Although the main assessment has a defined timescale, the national phase can be long and undefined	Undefined assessment timeline

What types of application (legal basis) can be submitted?

The legal provisions covering all procedures for human medicinal products are contained in Directive 2001/83/EC (as last amended by Directive 2004/24/EC and by Directive 2004/27/EC). This Directive provides a number of different legal bases by which to apply for an MA.

• according to Article 8(3) of Directive 2001/83/EC, relating to full applications containing all appropriate quality, nonclinical and clinical data;
• according to Article 10 of Directive 2001/83/EC, relating to generic medicinal products and similar biological medicinal products;
• according to Article 10a of Directive 2001/83/EC, relating to applications relying on well-established medicinal use supported by bibliographic literature;
• according to Article 10b of Directive 2001/83/EC, relating to applications for new fixed combination products;
• according to Article 10c of Directive 2001/83/EC, relating to informed consent from a marketing authorisation holder for an authorised medicinal product.
• 
  

Orphan Medicinal Product Designation in the EU

What is an Orphan Medicinal Product?

What is an Orphan Medicinal Product Designation?

An Orphan Medicinal Product Designation (OMPD) is granted by the European Commission, subsequent to an initial opinion being made by the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products (COMP) that the product qualifies as an orphan medicinal product.

What are the criteria for orphan designation?

To qualify for orphan designation (as set out in Article 3 of (EC) No 141/2000), a product must meet one of the following criteria:

1. It is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 people in the EU at the time of submission of the application.
2. It is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition and, without incentives, it is unlikely that the revenue after marketing of the medicinal product would cover the investment in its development.

Additionally, irrespective of the criteria met above, either of the following must apply:

1. No satisfactory method of diagnosis, prevention or treatment of the condition concerned is authorised, or;
2. If a satisfactory method exists, the medicine in question must be of significant benefit to individuals affected by the condition.

When can an orphan designation be applied for?

An application for orphan medicinal product designation can be submitted to the EMA at any stage of development; however it must be before an application for marketing authorisation is made.

A sponsor can request orphan designation for a product even if a separate sponsor already holds a designation covering the indication in question. In this instance, the first to gain marketing authorisation would benefit from market exclusivity.

Orphan designation can be requested for new chemical entities (NCEs) and new biological entities (NBEs), but also for existing approved products when the designation concerns a new, potentially orphan, indication for that product.

Any application for orphan designation must be supported by a robust scientific justification of the medical plausibility of the intended use.

How much does an application for OMPD cost?

The EMA do not charge a fee for the designation procedure.

What are the incentives of gaining Orphan Medicinal Product Designation?

Gaining orphan designation for a medicinal product entitles sponsors to the following benefits and/or incentives:

10 years’ market exclusivity: Orphan medicinal products benefit from market exclusivity in the EU for 10 years after receiving a marketing authorisation. An extension of 2 years’ market exclusivity may be granted if paediatric studies are included in the marketing authorisation.

During the 10 (+2) year period, directly competitive similar products for the same indication cannot normally be placed on the market.

Protocol assistance: Protocol assistance (PA) is similar to the EMA Scientific Advice procedure. However, additional benefits are included for PA, and sponsors can take advantage of the following:

1. EMA Scientific Advice procedure, designed to help sponsors optimise development of their orphan medicinal product within the scope of the orphan indication
2. Protocol assistance, also enables sponsors to ask questions related to:
   • significant benefit over other satisfactory methods of treatment, diagnosis, or prevention of the indication in question
   • development of medicinal products for rare conditions (e.g. whether two products are deemed ‘similar medicinal products’)
   • study design related to clinical superiority over similar products in the same indication

This procedure can help applicants maximise the chances of their marketing authorisation application being successful.

Fee reductions: A special fund from the European Commission, agreed annually by the European Parliament, is used by the EMA to grant fee reductions for orphan medicinal products. Reduction of fees will be considered for all types of centralised activities, including applications for marketing authorisation, pre-authorisation inspections, variations and protocol assistance. For organisations holding both orphan designation and ‘SME status’ enhanced fee reductions are applicable.

Automatic access to centralised procedure: Medicinal products holding orphan designation are now required to apply through the centralised procedure in accordance with Article 3.1 of (EC) Regulation 726/2004.

EU-funded research: Sponsors developing orphan medicinal products may be eligible for grants from the EU and Member States’ programmes and initiatives supporting research and development, including the European Commission framework programme.

Points to consider in gaining orphan designation

There are several misconceptions about orphan designation for medicinal products, two of which are detailed below:

• In theory, regulators require the same level of proof of efficacy and safety for orphan drugs as for other drugs. There are examples of pivotal studies being accepted with reduced patient numbers; however, this is condition or drug-specific. Any development plans should be discussed with the EMA through Protocol Assistance procedures.
• Orphan designation will not automatically allow accelerated review for marketing authorisation, conditional approval or approval under exceptional circumstances. Applicants would still need to apply for such procedures.

How to obtain Orphan Medicinal Product Designation?

In order to benefit from the incentives provided for orphan products a sponsor must obtain orphan designation for the product by compiling an OMPD application and submitting this to the EMA. Applications are reviewed by the Committee for Orphan Medicinal Products (COMP) and an opinion on whether the medicinal product meets the criteria for orphan designation will be issued. The opinion is forwarded to the European Commission who makes the final decision on whether orphan designation will be granted.

What is the procedure for gaining orphan designation?

Notification of intent to submit: A sponsor should notify the EMA of their intent to submit an OMPDapplication in the form of a Letter of Intent at least two months in advance of the planned submission date; the Letter of Intent (and ultimately the final application package) should be submitted in accordance with EMA published timelines.

Pre-submission meeting: The OMPD application procedure also offers sponsors the opportunity of a pre-submission meeting with the EMA. It is highly recommended to use this free service as feedback from the EMA on draft OMPD applications can significantly improve the success of OMPDapplications. If a pre-submission meeting is required, this should be stated in the Letter of Intent.

Submission of OMPD application: Following the pre-submission meeting the application is refined and a final package submitted to the EMA. The EMA will validate the submission and, if necessary, the sponsor is given three months to address any validation issues. The date of successful validation is taken as Day 1 of the procedure.

OMPD evaluation: The COMP will evaluate applications within 90 days of the start of procedure (i.e. post-validation) and will adopt either a positive or negative opinion at monthly held COMPmeetings.

At Day 60 the COMP will either:

• Adopt a positive opinion, or
• If a negative opinion is being considered, COMP will forward a list of questions to the sponsor. The sponsor will be advised as to whether written responses or an oral explanation will be required in time for the next COMP meeting

At Day 90 the COMP will either:

• Adopt a positive opinion to be forwarded to the European Commission, or
• In the absence of sufficient justification in the written response or oral explanation, adopt a negative opinion

On receipt of a negative opinion a sponsor can appeal. However, the intent to do so should be notified without delay. Negative opinions will be published on the EMA website, but the EMA offer the possibility of withdrawing applications likely to receive a negative opinion before adoption takes place at the COMP meeting.

Commission Decision: A positive opinion is forwarded to the European Commission and a Decision granted, typically within 30 days; in practice receipt of a Commission Decision can take 2-3 months following adoption of the COMP opinion.

Following receipt of the European Commission Decision a Public Summary of Opinion will be published on the EMA website and the orphan product will be included in the Community Register of Orphan Medicinal Products.

Timeline: The minimum timeframe from Letter of Intent to European Commission Decision is five months, although additional time may be required for validation responses, an oral/written explanation and European Commission Decision.

What information is required for OMPD applications?

In order to submit an application for orphan designation a sponsor (who can be an individual or an organisation) must have a fixed address in the European Union and is required to include the following documentation:

Key documentation

• Cover Letter – identifying sponsor, medicinal product, proposed orphan indication
• Application form – available on EMA website
  The common FDA/EMA application form can be used. However, it is important to note that there are key differences in the required supportive documentation for application in the two regions. Additionally, applications for designation will be reviewed separately by the respective Authorities.
• Core dossier – Parts A-F in accordance with guidance document ENTR/6283/00
  Part A: Description of the Condition
  Part B: Prevalence of the Condition
  Part C: Potential for return on Investment
  Part D: Existence of other methods of diagnosis, prevention or treatment
  Part E: Description of stage of development
  Part F: Bibliography
• Proof of Establishment in the EU
• Letter of Authorisation (if applicable)
• Translations of product name and proposed orphan indication into all official EU languages, plus Icelandic and Norwegian

Key components of application

The key components of the orphan designation application include the following:

Indication: the orphan indication must be a clearly defined, medically plausible, condition or disease. Sub-setting (or salami slicing) can be considered but only if it can be shown that the sub-set is medically plausible, and it can be demonstrated that the medicinal product would have no beneficial effects in the wider population. The orphan indication can be broader than the therapeutic indication proposed for a Marketing Authorisation Application.

Part A – Medical plausibility: this section must include a summary of the medicinal product and the proposed mechanism of action. The condition must be well defined and supported by published literature. Preliminary clinical and/or nonclinical data is required to support the notion that the product may be beneficial in the proposed orphan indication.

Part A – Justification of the life-threatening or debilitating nature of the disease or condition: the sponsor is expected to prove that the proposed orphan indication is life-threatening or debilitating in nature through the use of published literature.

Part B – Prevalence of the condition: in order to meet the prevalence designation criteria, the sponsor is required to demonstrate that less than 5 in 10,000 persons in the EU are affected by the disease or condition at the time of designation application. For products intended for diagnosis or prevention sponsors are required to show that less than 5 in 10,000 persons in the EU will receive or use the diagnostic. Prevalence data should be considered for all EU countries, as well as Iceland, Liechtenstein, and Norway.

Part D – Justification of significant benefit: in the application the sponsor must identify if there are any existing methods of diagnosis, treatment or prevention for the orphan indication. These could include Competent Authority approved methods or those commonly accepted by clinicians within the EU. If such methods exist, sponsors are required to demonstrate how the medicinal product under consideration could offer significant benefit in terms of improved safety, efficacy and/or improved pharmacokinetic properties.

What is required to maintain an OMPD?

In order to maintain orphan designation, sponsors are required to submit an Annual Report to theEMA within two months following the anniversary of the grant of the designation. The report should include details of:

• the progress of development since the initial application
• updated details of the current regulatory status
• any incentives received for development of the product

\When submitting a marketing authorisation application for a product with OMPD, applicants are expected to demonstrate that the OMPD criteria are still met, particularly with regards to significant benefit (if applicable). If these criteria are no longer met, the designation will be removed.

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com

Generic drugs in the EU

Process of reviewing and assessing the dossier to support a medicinal product in view of its marketing (also called licensing, registration, approval, etc.), obviously finalized by granting of a document also called marketing authorization (equivalent: product license). This process is performed within a legislative framework which defines the requirements necessary for application to the concerned (competent) regulatory authority, details on the assessment procedure (based on quality, efficacy and safety criteria) and the grounds for approval or rejection of the application, and also the circumstances where a marketing authorization already granted may be withdrawn, suspended or revoked.NOTE ^[1]

The application dossier for marketing authorization is called New Drug Application (NDA) in the USA or Marketing Authorization Application (MAA) in the European Union and other countries, or simply registration dossier. Basically, this consists of a dossier with data proving that the drug has quality, efficacy and safety properties suitable for the intended use, additional administrative documents, samples of finished product or related substances and reagents necessary to perform analyzes of finished product as described in that dossier. The content and format of the dossier must follow rules as defined by the competent authorities. For example, since year 2003, the authorities in the United States, the European Union and Japan ask for the Common Technical Document (CTD) format, and more recently, its electronic version - the electronic Common Technical Document (eCTD).

The application is filed with the competent drug regulatory authority in the concerned country, which can be either an independent regulatory body or a specialized department in the ministry of health.

In accordance with local legislation, the resulting document allowing to the applicant to market the product may be more detailed (in addition to data identifying the product and its holder it may contain addresses of all manufacturing sites, appended labeling, artwork of packaging components, etc.) until a one-page document called certificate of registration (and containing minimal data identifying the product and its source).

Many generic drugs are now being prescribed and the trend is increasing. For example, in Austria, the number of all generics prescriptions has more than doubled from 11% in 2000 to 23% in 2010. However, many myths and questions about generic drugs remain and information may be difficult to come by. It is therefore not surprising, as we have discovered in recent years, that even physicians and pharmacists are not always fully up to date in their understanding of generic drugs. Some of their questions centre on issues such as: are generic drugs really as good as the original; are we really dealing with an adequately tested, high quality medicinal product.

Today, generic drugs present an equally well-tolerated and efficacious alternative to established medicinal products, which contain well-known, rigorously tested active ingredients. An established originator product undergoes expensive and protracted development (up to 15 years) with inherently high preclinical and clinical research costs in order to be given market approval. The development of generic drugs, on the other hand, is relatively quick and inexpensive, which allows generic drugs to be sold at a distinctly cheaper price. This is due to the waiving of new preclinical and clinical studies, aside from some bioequivalence studies. Their lower price however should not be equated with ‘cheap quality’. In fact, generic medicines undergo the same strict scrutiny by the European or national medicines authorities as reference products.

 This marketing authorisation validates the safety, efficacy, and quality of a generic drug.

What makes a generic medicinal product generic?

The definition, according to Austrian drug law/the Medicinal Products Act as well as to EU Directive 2001/83/EC, is that a generic medicinal product ‘is a product which has the same qualitative’, i.e. kind of active substance, ‘and quantitative’, i.e. amount of active substance, ‘composition as the reference medicinal product’. For the sake of simplicity, the reference product is often also referred to as the originator. The different salts, esters, or derivatives of an active substance are considered to be the same active substance, unless they differ significantly in their safety and/or efficacy properties. In these cases, the manufacturer of a generic drug has to submit further proof of efficacy and safety.

The pharmaceutical form, which means the distinct way a product is to be administered, of the generic medicinal product has to be the same as for the reference medicinal product [1]. However, remarkably the various types of immediate release oral pharmaceutical forms, e.g. tablets, capsules and dragées, are considered to be one and the same pharmaceutical form. A patient prescribed with a particular medicinal product may therefore be prescribed either a film-coated tablet or a capsule of the same drug by his physician. This in itself does not pose a problem, as the galenic formulation may indeed be different, but the impact on the safety and efficacy profile of the whole product has been judged to be comparable during the approval procedure.

Are different compositions possible?

Differences in composition between the generic and reference medicinal product are possible, but only regarding the excipients, e.g. bulking agents, colouring agents; and not for the active substances. For example, corn starch may be used instead of lactose as an excipient. However, it has to be demonstrated by the applicant of the generic drug that these differences in composition do not influence the therapeutic efficacy and safety or how the drug is absorbed, distributed, metabolised or eliminated by the body, i.e. the drug’s pharmacokinetics must also remain more or less the same.

Bioavailability or bioequivalence trials need to be conducted in order to demonstrate the equivalence between the generic medicinal product and the reference medicinal product. Differences in the manufacturing process compared to the originator are allowed, but the same strict general quality criteria, e.g. controlled production under good manufacturing practice (GMP), apply to the production of the generic medicinal product as well as for the reference product. 

Also a medicinal product can only be considered as the reference product if it has been granted market approval in at least one Member State of the European Economic Area. However, only the so-called originator can serve as the reference product in bioequivalence testing, but never another generic drug, as this would otherwise mean the allowance of a copy of a copy.

How soon can generic medicinal products appear on the market?

The applicant needs to provide proof that the originator product has been authorised for at least eight years, or that the originator company has issued a written informed consent stating that the generics company is permitted to apply for its generic drugs sooner. As a rule however, the earliest a generic medicinal product is allowed to go on sale is 10 years after the first European originator is granted marketing authorisation. This 10-year market exclusivity can be extended by an additional year if, during the first eight years, the marketing authorisation holder of the originator obtains an additional authorisation for one or more new relevant therapeutic indications [2]. Figure 1 shows the ‘8+2 (+1) Formula’ applicable to generic medicinal products entering the market.

Some originators, however, hold patents—in some cases up to 1,000 patents for one single product were found—which can further postpone the launch of a generic drug. Such delay in market access is therefore possible, even if the marketing authorisation has already been granted to the generic drug. Notably, some misuse of patent strategies was described in the final report of the 2009 sector inquiry of the European Commission for Competition [3]. In a sample of 219 molecules from 2000 to 2007 there were reportedly 1,300 patent-related out-of-court disputes related to the launch of a generics. 

The number of patent litigations brought to court totalled nearly 700 cases in these seven years and the number of cases increased by a factor of four between 2000 and 2007. The report reached the conclusion that the behaviour and practices of originators contribute to generics delay as well as to difficulties in innovation itself because originators may even block each other.

What is a bioequivalence study?

Bioequivalence studies are often the demanded basis for granting marketing authorisation for a generic medicinal product. They are clinical studies conducted in accordance with Austrian drug law as well as to EU Directive 2001/20/EC and provide data to demonstrate bioequivalence between a test product, i.e. the generic medicinal product, and a reference product, i.e. the originator. 

The rate and extent of absorption of the medicinal products and therefore the bioavailability of the active substance(s) are determined. It is a widely accepted regulatory assumption, even sometimes challenged by generics disputants, that equivalent plasma concentration time curves represent equivalent efficacy and safety. Therefore, if bioequivalence can be shown after the administration of the same molar dose, equivalence or assumption of so-called essential similarity of the two products in terms of efficacy and safety can be concluded.

What are the rules for conducting bioequivalence studies?

How exactly a bioequivalence study has to be conducted, and which requirements need to be taken into consideration, is laid out in detail in the European bioequivalence guideline, the revised version of which came into effect mid-2010. The guideline clearly specifies the requirements for the design, conduct, and evaluation of bioequivalence studies for all EU countries. Since 2001, when the first bioequivalence guideline was published, many additional aspects were identified which needed to be amended and improved. Minor issues were addressed in interim question and answer documents. 

After a three-year preparation period, the comprehensively revised version of the guideline came into effect in August 2010. The comments and suggestions of over 50 expert organisations and associations were worked into the 22 draft versions. The revised version therefore now reflects the most up-to-date state of knowledge, which is essential in issuing harmonised and standardised marketing authorisations across Europe. 

The aim of the guideline was to do away with the ambiguities of the past, which often led to lengthy discussions and differences in professional opinion between the countries and competent authorities of the EU. This also ensures the safety and efficacy of all generic drugs being granted marketing authorisation.

Are bioequivalence studies only used in the development of generic drugs?

Since the task of bioequivalence studies is to detect differences between formulations or pharmaceutical forms, they are indeed not only used as a basis for the licensing of generic medicinal products. In fact, originators may also use bioequivalence studies during their own development since the formulation first used in clinical trials is often not the same which later goes into large-scale market production. Bioequivalence studies are used in these cases to allow bridging of the results obtained in the clinical trials. The same principles in study conduct, data evaluation, and assessment of results by the authority are applied in such originator studies as in the above-described studies for generic drugs. Remarkably, essential similarity between an originator small-scale clinical trial product and a large-scale originator product later to be for sale has never been put in question by anyone. Considering media coverage sometimes casts massive doubt about generics and the way they are authorised, obviously there seems to be an unfounded contrast in the perception dependent on who—the originator company or the generics company—makes use of the bio – equivalence concept for the authorisation of one of their products. Assuming that the bioequivalence concept is valid and trustworthy for authorisation of a new originator product, the same should be applied to the authorisation of a generic drug.

Is the manufacturing quality the same for generic and originator products?

The same quality requirements apply to the manufacturing of generic drugs as for any other medicinal product. Production has to be performed in accordance with GMP and is strictly controlled by evaluating the manufacturing data and by inspections performed not only in Austria and the EU, but also all over the world including countries such as India and South Africa. As for any other medicinal product, quality deficiencies in individual batches are theoretically possible and therefore the Austrian Federal Office for Safety in Health Care as well as the other competent EU authorities closely monitor the quality of all authorised medicinal products on the market. This is achieved by the legal obligation of authorisation holders to inform the authority about every out-of-specification results or other problems in manufacturing and an additional quality-defect notification system involving all healthcare professionals. This guarantees that only high quality medicinal products are available, regardless of whether these products are originators or generics.

When is a generic drug granted market authorisation?

An Austrian or an EU marketing authorisation is only issued when the pharmacokinetic parameters of the generic drug are comparable to those of the reference product and bioequivalence has been successfully demonstrated. 

Furthermore, the overall benefits of the generic medicine need to outweigh its risks (positive risk–benefit ratio) and its excipients and the manufacturing process must have been demonstrated to not negatively influence its safety and efficacy. 

Last but not least, all internationally relevant quality standards and legal requirements have to be fulfilled before marketing authorisation can be granted.

Procedures for obtaining a marketing authorization

Authorization processes follow either a purely national procedure, with rules and requirements as per national legislation in force, as it occurs in most of countries worldwide, or should follow a centrally approval or a mutual recognition or decentralized procedure within the European Union.

Types of applications

The type of application may vary according to status of the active ingredient.

Thus, if the application concerns a new active ingredient (new active substance, new chemical entity, new molecular entity), one talks about a full application.

Once a new active ingredient authorized, any additional strengths, pharmaceutical forms, administration routes, presentations, as well as any variations (changes to the existing marketing authorization) and extensions shall also be granted an authorization or be included in the initial marketing authorization, being subject of an abridged application.NOTE ^[2]

Special consideration is to be given to application for authorization of biological products and biotechnology products,^[1] homeopathic products, herbal drugs, radionuclide generators, kits, radionuclide precursor radiopharmaceuticals and industrially prepared radiopharmaceuticals; in such instances, requirements are specific, in the meaning that they are special, more or less detailed, as per the nature of active ingredient.

Validity of marketing authorizations

In most countries, a marketing authorization is valid for a period of 5 years. After this period, one should apply for renewal of the marketing authorization, usually by providing minimal data proving that quality, efficacy and safety characteristics are maintained and the risk-benefit ratio of the medicinal product is still favourable. However, in the European Union, after one renewal, the marketing authorization shall remain valid for an unlimited period, unless the competent regulatory authority decides otherwise.NOTE ^[3]

If the marketing authorization is not renewed in a due time as requested by the local legislation, in order to maintain the pharmaceutical product on a market, one can apply for re-authorization (re-registration). In such situations, the applicant may be requested to submit the whole items necessary for a full application.

Marketing authorization may be withdrawn, suspended, revoked or varied by regulatory authorities if under normal conditions of use the benefit over risk ratio is no more favorable, the product is harmful, or if it lacks therapeutic efficacy; also, one of the above actions can be taken if the qualitative and quantitative composition or other qualitative aspects (control) are not as currently declared.

Marketing authorization may be also withdrawn, suspended or revoked if the marketing authorization holder or its representative does not fulfill other legal or regulatory obligations necessary to maintaining of product on the market, as per the legislation in force.

Also, the marketing authorization is withdrawn in the EU if the product is not placed on the market within next 3 consecutive years after granting of authorization or if it is no more marketed for 3 consecutive years (so-called “sunset clause”).NOTE ^[4]

Notes

1. ^ Jump up to:^a b http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Marketingauthorisations/index.htm#3
2. Jump up^ Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. Official Journal of the European Union, L 311, 28.11.2001, p. 67.
3. Jump up^ Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use. L 136, 30.4.2004, p. 34.
4. Jump up^ CMD(h) Agreement on Sunset Clause and its application to MAs granted in more than one Member State. Co-ordination Group for Mutual Recognition and Decentralised Procedures -Human, December 2006.

References

1. European Medicines Agency. CPMP/EWP/QWP/1401/98 Rev.1. Guide line on the investigation on bioequivalence. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf
2. European Commission. Guidance on elements required to support the significant clinical benefit in comparison with existing therapies of a new therapeutic indication in order to benefit from an extended (11 years) marketing protection period, 2007. Available from: http://ec.europa.eu/health/files/eudralex/vol-2/c/guideline_14-11-2007_en.pdf
3. European Commission Competition, EU Sector inquiry, 8 July 2009. Available from: http://ec.europa.eu/competition/sectors/pharmaceuticals/inquiry/communication_en.pdf
4. Tschabitscher D, Platzer P, Baumgärtel C, Müllner M. Generic drugs: quality, efficacy, safety and interchangeability. Wien Klin Wochenschr. 2008;120:63-9.
5. American Medical Association. Summaries and recommendations of Council on Scientific Affairs Reports. Generic drugs (CSA Rep 6, A-02). 2002 Annual Meeting of the American Medical Association. 2002:13-4.
6. Henney JE. Review of generic bioequivalence studies from the food and drug administration. JAMA. 1999;282:1995.
7. Nwakama PE. Generic drug products demonstrate small differences in bioavailability relative to brand name counterparts: review of approved ANDAs, FDA. 2005.
8. Davit BM, et al. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the FDA. Ann Pharmacother. 2009 Oct; 43(10):1583-97.
9. Statement of the Austrian Society of Cardiology (ÖKG) regarding Clopidogrel-Generics. 2010. Available from: http://kardiologie-gefaessmedizin.universimed.com/artikel/stellungnahme-der-%C3%B6sterr-kardiologischen-gesellschaft-%C3%B6kg-zu-clo
10. Consensus statement of Austrian Society of Biologic Psychiatry (ÖGBP), Generics and originators in psychiatry, 2008. Available from: http://www.medizin-medien.at/mm/mm011/low-generika.pdf

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com

Intellectual Property (IP) Value Realization

IP-driven companies thoroughly and vigorously develop a Technology Value Realization (IP Commercialization) process to a level of sophistication such that they can predict with a reasonably high degree of accuracy the market success for their emerging technologies. This process links the stages of moving a technology with product potential to patent procurement/ management. In the four phases of technology commercialization, there are parallel patent value realization activities.

Bringing Patent Protected Technology to Market

The process begins in the Research & Development (R&D) labs where technology with product potential is identified. It is at this early point that the linkage with the patent process is formed.

Commercialization Process	Patent Process
I. Technology Analysis Process	I. Patent Search
Starts with an analysis of the technology followed by the development of a draft Technical Product Description	Patent searches are done for prior art Provisional patents may be filed
II. Market Opportunity Identification	II. Patent Application
Market opportunity identification Competitive analysis Draft Business Case Final Technical Product Description Initial patent value determination is made	Patent application is registered with the Patent and Trademark offices of the US (and other countries) for value added features Patent Issued (or rejected)
III. Market Actualization Planning	III. Patent Profit Planning
Most effective method(s) for value realization/commercialization are determined	Develop licensing strategies and Patent Licensing Agreements (PLAs)
IV. Implementation	IV. Patent Management
Commercialization and appoint of a Product Manager (or market manager) to transition the technology into implementation and bring it to market	Associated patent(s) are then moved into Patent Management

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com

PARIS CONVENTION

The Paris Convention, signed in 1883 was one of the first IP treaties and now has over 170 signatory countries of which the US is one. The fundamental benefit of this treaty is that the filing date of a patent application filed in any one of the convention countries can serve as the priority date for patent applications filed within one year in any other member country. There are other treaties with similar reciprocal priority rights. The US, for example, has one with Taiwan.

The Paris Convention
As we discussed, the Paris Convention is an international treaty that allows applicants to file a first application in their home country. That application is referred to as a priority document or filing, and the date it is filed is called the priority date.
The priority filing starts a 12-month period within which a further application called a Paris Convention application (or a direct application claiming priority) can be filed elsewhere, claiming Paris Convention priority back to the priority date. To the extent that the content of the Paris Convention application is disclosed in the earlier priority document, it will be backdated to the priority date.
The advantages of using the Paris Convention are well known to those familiar with the patent process. The 12-month convention period lets the applicant seek funding, perform market research and turn an idea into a commercial product. All of these can be done following a single filing without risking a loss of rights in other countries.
If the Paris Convention didn’t exist, applicants would need to coordinate simultaneous filing in all countries that are of potential interest at the very start of the process. This would be complicated and costly, bearing in mind the need for translations in many countries.
- See more at: http://info.inovia.com/2013/02/the-paris-convention-versus-the-pct/#sthash.AtieuxW4.dpuf

 

The Paris Convention
As we discussed, the Paris Convention is an international treaty that allows applicants to file a first application in their home country. That application is referred to as a priority document or filing, and the date it is filed is called the priority date.
The priority filing starts a 12-month period within which a further application called a Paris Convention application (or a direct application claiming priority) can be filed elsewhere, claiming Paris Convention priority back to the priority date. To the extent that the content of the Paris Convention application is disclosed in the earlier priority document, it will be backdated to the priority date.
The advantages of using the Paris Convention are well known to those familiar with the patent process. The 12-month convention period lets the applicant seek funding, perform market research and turn an idea into a commercial product. All of these can be done following a single filing without risking a loss of rights in other countries.
If the Paris Convention didn’t exist, applicants would need to coordinate simultaneous filing in all countries that are of potential interest at the very start of the process. This would be complicated and costly, bearing in mind the need for translations in many countries.
- See more at: http://info.inovia.com/2013/02/the-paris-convention-versus-the-pct/#sthash.AtieuxW4.dpuf

The Paris Convention
As we discussed, the Paris Convention is an international treaty that allows applicants to file a first application in their home country. That application is referred to as a priority document or filing, and the date it is filed is called the priority date.
The priority filing starts a 12-month period within which a further application called a Paris Convention application (or a direct application claiming priority) can be filed elsewhere, claiming Paris Convention priority back to the priority date. To the extent that the content of the Paris Convention application is disclosed in the earlier priority document, it will be backdated to the priority date.
The advantages of using the Paris Convention are well known to those familiar with the patent process. The 12-month convention period lets the applicant seek funding, perform market research and turn an idea into a commercial product. All of these can be done following a single filing without risking a loss of rights in other countries.
If the Paris Convention didn’t exist, applicants would need to coordinate simultaneous filing in all countries that are of potential interest at the very start of the process. This would be complicated and costly, bearing in mind the need for translations in many countries.
- See more at: http://info.inovia.com/2013/02/the-paris-convention-versus-the-pct/#sthash.AtieuxW4.dpuf

The Paris Convention for the Protection of Industrial Property, signed in Paris, France, on 20 March 1883, was one of the first intellectual property treaties. It established a Union for the protection of industrial property. The Convention is still in force as of 2014. The substantive provisions of the Convention fall into three main categories: national treatment, priority right and common rules. ^[1]

National treatment

According to Articles 2 and 3 of this treaty, juristic and natural persons who are either national of or domiciled in a state party to the Convention shall, as regards the protection of industrial property, enjoy in all the other countries of the Union, the advantages that their respective laws grant to nationals.
In other words, when an applicant files an application for a patent or a trademark in a foreign country member of the Union, the application receives the same treatment as if it came from a national of this foreign country. Furthermore, if the intellectual property right is granted (e.g. if the applicant becomes owners of a patent or of a registered trademark), the owner benefits from the same protection and the same legal remedy against any infringement as if the owner was a national owner of this right.

Priority right

The "Convention priority right", also called "Paris Convention priority right" or "Union priority right", was also established by Article 4 of this treaty. It provides that an applicant from one contracting State shall be able to use its first filing date (in one of the contracting State) as the effective filing date in another contracting State, provided that the applicant files a subsequent application within 6 months (for industrial designs and trademarks) or 12 months (for patents and utility models) from the first filing.

History

After a diplomatic conference in Paris in 1880, the Convention was signed in 1883 by 11 countries: Belgium, Brazil, France, Guatemala, Italy, the Netherlands, Portugal, El Salvador, Serbia, Spain and Switzerland. Guatemala, El Salvador and Serbia denounced and reapplied the convention via accession.^[2]
The Treaty was revised at Brussels, Belgium, on 14 December 1900, at Washington, United States, on 2 June 1911, at The Hague, Netherlands, on 6 November 1925, at London, United Kingdom, on 2 June 1934, at Lisbon, Portugal, on 31 October 1958, and at Stockholm, Sweden, on 14 July 1967, and was amended on 28 September 1979.

Contracting parties

Main article: List of parties to the Paris Convention for the Protection of Industrial Property

Paris Convention members (in green)

As of September 2014, the Convention has 176 contracting member countries,^[3] which makes it one of the most widely adopted treaties worldwide. Notably, Taiwan and Burma are not parties to the Convention. However, according to Article 27 of its Patent Act, Taiwan recognizes priority claims from contracting members.
Contracting members include: Albania; Algeria; Andorra; Angola; Antigua and Barbuda; Argentina; Armenia; Australia; Austria; Azerbaijan; Bahamas; Bahrain; Bangladesh; Barbados; Belarus; Belgium; Belize; Benin; Bhutan; Bolivia; Bosnia and Herzegovina; Botswana; Brazil; Brunei Darussalam, Bulgaria; Burkina Faso; Burundi; Cambodia; Cameroon; Canada; Central African Republic; Chad; Chile; China; Colombia; Comoros; Congo; Costa Rica; Croatia; Cuba; Cyprus; Czech Republic; Côte d'Ivoire; Democratic People's Republic of Korea; Democratic Republic of the Congo; Denmark; Djibouti; Dominica; Dominican Republic; Ecuador; Egypt; El Salvador; Equatorial Guinea; Estonia; Finland; France; Gabon; Gambia; Georgia; Germany; Ghana; Greece; Grenada; Guatemala; Guinea; Guinea-Bissau; Guyana; Haiti; Holy See; Honduras; Hungary; Iceland; India; Indonesia; Iran (Islamic Republic of); Iraq; Ireland; Israel; Italy; Jamaica; Japan; Jordan; Kazakhstan; Kenya; Kuwait; Kyrgyzstan; Laos; Latvia; Lebanon; Lesotho; Liberia; Libya; Liechtenstein; Lithuania; Luxembourg; Macedonia;^[4] Madagascar; Malawi; Malaysia; Mali; Malta; Mauritania; Mauritius; Mexico; Moldova; Monaco; Mongolia; Montenegro; Morocco; Mozambique; Namibia; Nepal; Netherlands; New Zealand; Nicaragua; Niger; Nigeria; Norway; Oman; Pakistan; Panama; Papua New Guinea; Paraguay; Peru; Philippines; Poland; Portugal; Qatar; Republic of Korea; Romania; Russian Federation; Rwanda; Saint Kitts and Nevis; Saint Lucia; Saint Vincent and the Grenadines; Samoa; San Marino; Sao Tome and Principe; Saudi Arabia; Senegal; Serbia; Seychelles; Sierra Leone; Singapore; Slovakia; Slovenia; South Africa; Spain; Sri Lanka; Sudan; Suriname; Swaziland; Sweden; Switzerland; Syrian Arab Republic; Tajikistan; Thailand; Togo; Tonga; Trinidad and Tobago; Tunisia; Turkey; Turkmenistan; Uganda; Ukraine; United Arab Emirates; United Kingdom; United Republic of Tanzania; United States of America; Uruguay; Uzbekistan; Venezuela; Vietnam; Yemen; Zambia; and Zimbabwe.
Former member states: Austria-Hungary (succeeded by Austria and Hungary); Czechoslovakia; Orange Free State 1899–31 May 1902; Colony of Queensland (1891–1900, after federation acceded to by Australia); Serbia and Montenegro (succeeded by Serbia); Soviet Union (succeeded by the Russian Federation); and Yugoslavia (succeeded by Serbia and Montenegro and then Serbia).

Administration

The Paris Convention is administered by the World Intellectual Property Organization (WIPO),^[5] based in Geneva, Switzerland.^[6]

References

1. "Summary of the Paris Convention". WIPO. Retrieved 2014-12-06.
2. "Contracting Parties to the Paris Convention". WIPO. Retrieved 2012-12-30.
3. "Contracting Parties > Paris Convention (Total Contracting Parties : 176)". World Intellectual Property Organization (WIPO). Retrieved 12 September 2014.
4. Signed as "the former Yugoslav Republic of Macedonia"
5. WIPO web site, WIPO-Administered Treaties. Consulted on 10 August 2007.
6. WIPO web site, What is WIPO?. Consulted on 10 August 2007.

Further reading

• G.H.C. Bodenhausen, Guide to the Application of the Paris Convention for the Protection of Industrial Property As Revised at Stockholm in 1967, (World Intellectual Property; 1 February 1968) ISBN 92-805-0368-5
• Die Unionspriorität im Patentrecht, Grundfragen des Artikels 4 der Pariser Verbandsübereinkunft, Dr. Reinhard Wieczorek, 1975, Köln, C. Heymanns, ISBN 3-452-17822-6

External links

• Paris Convention at the World Intellectual Property Organization (WIPO)
• Haberman v Comptroller, a UK court decision that helps to understand the concept of priority.
• Priority under the European Patent Convention Explanation of the priority rules as they apply at the European Patent Office.

  
Rue de la Convention from Pont Mirabeau



paris











DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com