Under surveillance: generic and biosimilar MAs
Regulatory surveillance includes a variety of options for drug companies and other stakeholders to monitor future and pending marketing authorisation applications (MAAs). EU regulatory surveillance allows companies to monitor whether generic or biosimilar MAAs are pending in the EU. This allows companies to prepare for the launch of a competitor product or potential advocacy and litigation activities. Such activities should be carefully considered in light of competition law, and may be aimed at protecting regulatory data protection and market exclusivity rights, and/or patent and supplementary protection certificates.
The surveillance options depend on the type of MAA procedure that is followed. The centralised procedure—which is based on Regulation (EC) No. 726/2004—provides for a single application, evaluation and authorisation allowing direct access to the entire EU market. The centralised procedure is mandatory for certain medicinal products, eg, those intended to treat cancer, diabetes, HIV, and medicinal products derived from biotechnology processes such as genetic engineering, etc.
The centralised procedure is optional for other medicinal products, eg, in the interest of public health at an EU level if the reference product was approved at that level, etc. MAAs for medicinal products that fall within neither the mandatory scope nor the optional scope should be submitted through either the decentralised procedure, mutual recognition or national procedure at EU member state level.
Many biosimilars fall within the mandatory scope of the centralised procedure.
Available information
For MAAs submitted through the centralised procedure, the European Medicines Agency (EMA) publishes a monthly list of pending applications. For biosimilars, this list includes information on the international non-proprietary name and therapeutic area. In addition, information on envisaged MAAs may become apparent from an applicant’s requests regarding paediatric investigation plans, which may also be published on the EMA’s website, before the actual MAA is submitted.
Once a marketing authorisation (MA) is granted this is published in the Community Register of medicinal products and the Official Journal of the EU. The EMA must publish the European public assessment report of the Committee for Medicinal Products for Human Use.
For MAAs submitted through the decentralised procedure, mutual recognition or national procedure—which is based on Directive 2001/83/EC—the possibilities for obtaining information vary according to the relevant EU member state. This is because MAAs through the decentralised procedure, mutual recognition or national procedure all lead to one or more national MAs.
“Publicly available information on clinical trials such as clinical trial databases may also be a valuable source of information, especially in respect of (envisaged) biosimilar MAAs.”
Directive 2001/83/EC provides for the obligation of EU member states to make the following documents publicly available: the decision granting the MA, the patient information leaflet, the summary of product characteristics and the public assessment report.
In some EU member states the national competent authorities publish information on their website about whether any MAAs are pending, eg, in Finland and Portugal. Some countries do not disclose anything on pending applications, eg, Spain and the UK. The MRI Product Index published by the heads of medicines agencies includes medicines approved in EU member states according to the mutual recognition and decentralised procedures.
MAAs through the decentralised procedure and mutual recognition procedure should be granted a national MA within 30 days after closing the procedure. However, in practice this 30-day deadline is not met by many EU member states and the periods that are applied for granting the actual MAs may differ between various states.
Publicly available information on clinical trials such as clinical trial databases may also be a valuable source of information, especially in respect of (envisaged) biosimilar MAAs.
In many EU member states, it is possible to submit a request for information to the competent authorities on the basis of their national freedom of information (FOI) legislation. The content of these requests is a series of various questions regarding pending and withdrawn MAAs. Depending on the outcomes and responses it may be worthwhile to send repeat and/or follow-up requests on a regular basis.
Pursuant to Regulation (EC) No. 1049/2001 regarding public access to European Parliament, Council and Commission documents (FOI regulation), a request for access to documents may also be submitted at the EMA. However, as a general policy the EMA does not disclose any more information on the fact that an MAA is pending than the information that is included in the monthly update lists.
Putting it all together
All the various pieces of information gathered from public sources, FOI requests and through general intelligence may together lead to very interesting information on pending MAAs. Such information may put a company in a good position to be well prepared for what’s ahead.
Information gathered through surveillance may lead to follow-up actions, such as advocacy activities or even litigation. Advocacy may potentially lead to delays in the entry of a generic or biosimilar medicinal product. In light of this it is important that advocacy options are carefully considered and are based on valid and well substantiated arguments to ensure that exercising such advocacy options cannot conflict with competition law.
If there are valid and substantiated reasons that are relevant to be brought forward there are various options. Generally the MA holder of a ‘reference medicinal product’ has the right to challenge the decision authorising a generic or biosimilar medicinal product that refers to that reference product on the basis of data exclusivity rights.
However, the question of whether the MA holder of a reference product—or less direct, the MA holder of a competitive product—actually has legal standing and to what extent varies per EU member state. It may be worthwhile to get a good overview of the options of EU member states as in certain states a competitor may be qualified as an interested party and authorised to present its views even before a decision regarding the grant of an MA is actually taken, eg, in the Netherlands.
Generally a competitor or other party will not have legal standing in the situation that no decision was taken to grant an MA. But if there is knowledge that a generic or biosimilar MAA is pending there are various options to present valid and substantiated arguments. As a first step the arguments can be further detailed in a letter or even more substantial document which can be submitted to the relevant competent authority or authorities if it concerns a decentralised or mutual recognition procedure.
Further to such initial steps, a meeting can be requested to elaborate on and discuss any objections that there may be against an MAA. Such written arguments can also be shared with the European Commission or a member of European Parliament; this may be an interesting option if the objections are of a fundamental, legal or policy nature. If applicable, such views may also be shared by a stakeholder’s organisation on a more general level.
The question of whether competent authorities or others involved will be open for such arguments will depend on the nature of the arguments and may also vary on an EU member state level. For potential future litigation it is helpful to get prepared well ahead and to communicate one and the same story consistently to all different competent authorities and others involved in the EU.
Having a regulatory surveillance programme may be of high value to ensure good intelligence early on and be well prepared before an MA is actually granted.
Ruth Franken is a senior associate at Hogan Lovells in Amsterdam. She can be contacted at: ruth.franken@hoganlovells.com
