The roles and responsibilities of the legal representative set out under Clinical Trials Directive 2001/20/EC are likely to change under the new Clinical Trials Regulation 536/2014. These changes are likely to affect how non EU sponsors of clinical trials approach the appointment of the legal representative in order to comply with the sponsor's obligations pursuant to the Regulation.

Clinical Trials Directive 2001/20/EC (the "CTD 2001")

Under the CTD 2001, sponsors of clinical trials who are not based in the EEA are required to appoint a legal representative that is based in the EEA. In the UK, the CTD 2001 was implemented through the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031).

When the CTD 2001 was implemented in the UK, the role of the legal representative with respect to sponsors was provided by the competent authority, being the Medicines and Healthcare Products Regulatory Agency ("MHRA"). The role of the legal representative was limited to a contact person for communications and in practice, the UK legal representative of a non-EU sponsor did not assume any of the legal liabilities of the sponsor(s) for the clinical trial by virtue of being the legal representative and did not therefore require insurance or indemnity to meet such liabilities.

Clinical Trials Regulation 536/2014 (the "CTR 2014")

The final version of the CTR 2014 was published on 27 May 2014. With respect to the role of the legal representative of a sponsor not established in the EU, Article 74(1) of the CTR 2014 states:

"Where the sponsor of a clinical trial is not established in the Union, that sponsor shall ensure that a natural or legal person is established in the Union as its legal representative.  Such legal representative shall be responsible for ensuring compliance with the sponsor's obligations pursuant to this Regulation, and shall be the addressee for all communications with the sponsor provided for in this Regulation.  Any communication to that legal representative shall be deemed to be a communication to the sponsor"

Role of the legal representative under CTR 2014

It appears therefore that under CTR 2014, the role of the legal representative appears much more onerous. It requires the legal representative to ensure that the non-EU sponsor complies with their obligations under the CTR 2014.

It is not clear whether there is a distinction between the sponsor's obligations and the liabilities or penalties attached to failure to meet those obligations, and the obligation of the legal representative to ensure compliance of the sponsor with those same obligations.  It is possible there is a separate liability, with presumably lesser consequences, for failing to ensure compliance by the sponsor.

To an extent this is supported by the statements immediately following in Article 75 that the liabilities of the sponsor and principal investigator are not affected by "this Chapter" (which includes the legal representative provisions).

Role of the contact person under CTR 2014

Under CTR 2014, sponsors not established in the EU are still required to have at least a contact person in the EU. Under CTR 2014, the role of the contact person appears to be similar to the role of the legal representative as it came to be interpreted under CTD 2001. The contact person role under the CTR 2014 is more administrative and is to act as the addressee for all communications with the non-EU sponsor.

In contrast to the requirements of the legal representative,  it is notable that the CTR 2014does not appear to require the contact person to ensure the non-EU sponsor's compliance with their obligations under the CTR 2014.

Furthermore, whilst not specifically stated in CTR 2014, from the wording of the preamble to the CTR 2014 and subject to Member State interpretation, if the task carried out by the contact person is not considered to be a "delegated" task [under Article 75 of CTR 2014] of the non-EU sponsor, then it is unlikely a contact person could be subject to criminal or civil liability.

Can there be a legal representative or a contact person for non-EU sponsors?

CTR 2014 states that each Member State can determine whether it requires a legal representative or a contact person for non-EU sponsors (or possibly the option of both).  At Article 74(2) of the CTR 2014 it states that:

"Member States may choose not to apply paragraph 1 [of Article 74] as regards clinical trials to be conducted solely on their territory, or on their territory and the territory of a third country, provided that they ensure that the sponsor establishes at least a contact person on their territory in respect of that clinical trial who shall be the addressee for all communications with the sponsor provided for in this Regulation."

Conclusions

The CTR 2014 is not expected to come into force any time prior to May 2016.  In the meantime, one would expect Member States to clarify whether they will be requiring non-EU sponsors to have a legal representative or contact person in the EU. 

Given some of the context of why CTR 2014 was being introduced, i.e. to encourage more EU and cross Member State trials, one would expect most Member States, in the interests of their own attractiveness to sponsors, not to opt for the more onerous role of a legal representative rather than a contact person under the CTR 2014. 

With regard to UK, neither the MHRA nor the Human Research Authority (HRA) have yet to announce any changes that will be made to the current role of legal representative.  Given the way the UK implemented the CTD 2001 and the current requirements, one might expect it unlikely that the UK would opt for the legal representative under the CTR 2014, but would instead opt for the contact person (largely the status quo) or possibly allow the non-EU sponsor the ability to choose either a legal representative or a contact person.

Until the Member States, including the UK, set out their position regarding whether a legal representative or a contact person (or either) is required under CTR 2014, it is not possible to firmly state whether there would be any exposure to civil and criminal liability. Furthermore, it is not possible to state precisely what the civil or criminal liability exposure might be, as this has also been left to the discretion of the Member States.

The issues highlighted above in relation to the role of the legal representative are points to keep in mind and consider, while we await more information and guidance from the regulatory authorities in the Member States.