Roche Registration Ltd, R (on the application of) v The Secretary of State for Health [2015] EWCA Civ 1311

“2. Roche is a wholly owned subsidiary of Roche Holding AG and is the marketing authorisation holder ("MAH") of all centrally-approved medicinal products developed and marketed by the Roche group of companies. The MHRA discharges the Secretary of State's duties and powers as the "licensing authority" for Great Britain under the Human Medicines Regulations 2012 ("the 2012 Regulations") which implement Directive 2001/83/EC of the European Parliament and of the Council ("the 2001 Directive"). The European Medicines Agency ("the EMA") appears as an interested party. The EMA was set up under Regulation (EC) 726/2004 ("the 2004 Regulation") and is responsible for co-ordinating the scientific resources put at its disposal by Member States for the evaluation, supervision and pharmacovigilance of medicines authorised centrally. It includes the Committee for Medicinal Products for Human Use ("the CHMP"), which is responsible for preparing the opinion of the EMA on any question relating to the evaluation of medicines, and the Pharmacovigilance Risk Assessment Committee ("PRAC"), which is responsible, amongst other things, for providing recommendations to the CHMP on any question relating to pharmacovigilance activities for human medicines. … 4. The Re-Inspection related to Roche's pharmacovigilance system and the extent to which Roche had complied with its reporting obligations. Pharmacovigilance is the science and activities relating to the detection, reporting, assessment, understanding and prevention of adverse effects of a medicine or any other medicine-related problem. The obligation on MAHs, such as Roche, to operate a pharmacovigilance system is a critical element of the system of licensing human medicines in the European Union ("EU"). In broad terms, MAHs are obliged to operate a pharmacovigilance system and to audit that system. They are also obliged to monitor suspected adverse reactions to their product and to record and report suspected adverse reactions to their product which are brought to their attention. These are central safeguards for public safety and health purposes. The duty to protect public health exists independently and separately from any disciplinary issues that may arise. 5. Medicines regulators, such as the MHRA, routinely exercise powers under their respective national laws to conduct pharmacovigilance inspections to check compliance with pharmacovigilance obligations. Where deficiencies are identified, the company under inspection proposes and then implements corrective and preventative actions ("CAPAs"). The regulatory body may then re-inspect at a later date to confirm proper implementation. Roche states that it was (and remains) content to comply with such inspections. Additionally, the CHMP routinely requests that national competent authorities conduct inspections in respect of products for which the CHMP is responsible. Roche states that it was (and remains) content to comply with such inspections. 6. The two principal pieces of EU legislation which impose pharmacovigilance obligations on MAHs are the 2004 Regulation and the 2001 Directive. With effect from July 2012 that legislation underwent material amendment, as did the manner in which the EU laws are implemented into UK law. Prior to August 2012 the key national legislation was the Medicines Act 1968 ("the Act") and the Medicines for Human Use (Marketing Authorisations etc.) Regulations 1994 ("the 1994 Regulations"). The 2012 Regulations repealed and/or replaced the relevant provisions of the Act and the 1994 Regulations. The pharmacovigilance obligations said by Roche to be relevant to this claim are those pre-dating July 2012, largely to be found in the 2004 Regulation. The Re-Inspection was conducted in late 2013 pursuant to the 2012 Regulations. 7. Roche alleges that, when conducting the Re-Inspection, the MHRA was knowingly gathering evidence in the context and for the purpose of infringement proceedings which have been brought against Roche under the Penalties Regulation (EC) No. 658/2007 ("the Penalties Regulation") ("the infringement proceedings"). These proceedings are of a criminal or quasi-criminal nature and carry a heavy potential financial penalty of up to 5% of Roche's annual EU turnover in the preceding year. It appears that this is the first time that an investigation has been launched under the Penalties Regulation. 8. Article 1 of Chapter 1 of the Penalties Regulation identifies various pharmacovigilance obligations which, if infringed, give rise to a risk of a financial penalty being imposed. Chapter II sets out the "Infringement Procedure" which commences with an "Inquiry" by the EMA which leads to the EMA producing a report which summarises its findings. The "Decision-Making stage" follows next. The European Commission ("the Commission") considers the case and may, having followed the procedure provided for in the Penalties Regulation, adopt a decision imposing a fine. The Penalties Regulation also allows for penalties to be imposed for non-compliance with measures of inquiry. It provides at the outset (by recital 13) that, when carrying out the infringement procedure, the EMA and Commission must ensure the respect of the rights of defence. The MAH must have access to the file of the EMA and the Commission and the right to legal representation. The right to silence must also be respected. 9. The Claimant brings three grounds of challenge: a) first, that the MHRA provided information to the EMA pursuant to formal requests from the EMA under Article 8(3) of the Penalties Regulation. Article 8(3) did not provide a proper basis for such requests. Accordingly the MHRA's compliance with them was and remains ultra vires; b) secondly, that the MHRA failed properly to explain to Roche, at the time of the Re-Inspection, that the information was being obtained for use in a criminal or quasi-criminal investigation and that it would be making additional submissions to the EMA for that purpose. Had the MHRA done so, Roche would have been able to consider its position, including by seeking legal advice and representation and by asserting its right to silence and not to incriminate itself. The MHRA's conduct was thus procedurally improper and unlawful. There was no or insufficient procedural protection of Roche's rights in breach of the applicable EU, European Convention of Human Rights ("ECHR") and domestic law standards in the context of the infringement proceedings; c) thirdly, that the material provided by the MHRA to the EMA under the Article 8(3) requests (and otherwise under the Penalties Regulation) contained a number of fundamental errors of law. These are therefore public law challenges relating to vires, procedural fairness and alleged error of law. 10. Roche now seeks a declaration that: a) the past and continuing compliance by the MHRA with the EMA's Article 8(3) requests dated 1st October 2013 and 17th October 2013 is unlawful, as would be compliance with any other such request in the context of the infringement proceedings; b) the MHRA's conduct of the Re-Inspection was unlawful; c) the transmission of the resulting draft Re-Inspection Report by the MHRA to the EMA for the purpose of use in the infringement proceedings was unlawful; d) the transmission by the MHRA to the EMA of the final Re-Inspection Report for use in the infringement proceedings was unlawful; e) any information or other communication between the MHRA and the EMA in the context of the infringement proceedings in which the views of the MHRA are based on information gained during the Re-Inspection (including the MHRA's letter to the EMA dated 13th December 2013) was unlawful; f) that the findings of the MHRA in the Re-Inspection Report are unlawful.” a) first, that the MHRA provided information to the EMA pursuant to formal requests from the EMA under Article 8(3) of the Penalties Regulation. Article 8(3) did not provide a proper basis for such requests. Accordingly the MHRA's compliance with them was and remains ultra vires; b) secondly, that the MHRA failed properly to explain to Roche, at the time of the Re-Inspection, that the information was being obtained for use in a criminal or quasi-criminal investigation and that it would be making additional submissions to the EMA for that purpose. Had the MHRA done so, Roche would have been able to consider its position, including by seeking legal advice and representation and by asserting its right to silence and not to incriminate itself. The MHRA's conduct was thus procedurally improper and unlawful. There was no or insufficient procedural protection of Roche's rights in breach of the applicable EU, European Convention of Human Rights ("ECHR") and domestic law standards in the context of the infringement proceedings; c) thirdly, that the material provided by the MHRA to the EMA under the Article 8(3) requests (and otherwise under the Penalties Regulation) contained a number of fundamental errors of law. a) the past and continuing compliance by the MHRA with the EMA's Article 8(3) requests dated 1st October 2013 and 17th October 2013 is unlawful, as would be compliance with any other such request in the context of the infringement proceedings; b) the MHRA's conduct of the Re-Inspection was unlawful; c) the transmission of the resulting draft Re-Inspection Report by the MHRA to the EMA for the purpose of use in the infringement proceedings was unlawful; d) the transmission by the MHRA to the EMA of the final Re-Inspection Report for use in the infringement proceedings was unlawful; e) any information or other communication between the MHRA and the EMA in the context of the infringement proceedings in which the views of the MHRA are based on information gained during the Re-Inspection (including the MHRA's letter to the EMA dated 13th December 2013) was unlawful; f) that the findings of the MHRA in the Re-Inspection Report are unlawful.”

“Article 101 Member States shall operate a pharmacovigilance system for the fulfilment of their pharmacovigilance tasks and their participation in Union pharmacovigilance activities… Each Member State shall designate a competent authority for the performance of pharmacovigilance tasks….. Article 104 The [MAH] shall operate a pharmacovigilance system for the fulfilment of his pharmacovigilance tasks equivalent to the relevant Member State’s pharmacovigilance system provided for under Article 101(1)…”

“…The supervisory authorities for pharmacovigilance shall be responsible for verifying on behalf of the Union that the [MAH] for the medicinal product satisfies the pharmacovigilance requirements laid down in Titles IX and XI of [the 2001 Directive].”

“SUPERVISION AND SANCTIONS Article 111 The competent authority of the Member State concerned shall, in cooperation with the Agency, ensure that the legal requirements governing medicinal products are complied with by means of inspections, if necessary unannounced, and, where appropriate, by asking an Official Medicines Control Laboratory or a laboratory designated for that purpose to carry out tests on samples. This cooperation shall consist in sharing information with the Agency on both inspections that are planned and that have been conducted. Member States and the Agency shall cooperate in the coordination of inspections in third countries. The inspections shall include but not be limited to the ones mentioned in paragraphs 1a to 1f. … 1b.The competent authority of the Member State concerned shall have a system of supervision including by inspections at an appropriate frequency based on risk, at the premises of the manufacturers, importers, or distributors of active substances, located on its territory, and effective follow-up thereof. Whenever it considers that there are grounds for suspecting non-compliance with the legal requirements laid down in this Directive, including the principles and guidelines of good manufacturing practice and good distribution practices referred to in point (f) of Article 46 and in Article 47, the competent authority may carry out inspections at the premises of: (a) manufacturers or distributors of active substances located in third countries; (b) manufacturers or importers of excipients… 1g. Inspections shall be carried out by officials representing the competent authority who shall be empowered to: ... (d) inspect the premises, records, documents and pharmacovigilance system master file of the marketing authorisation holder or any firms employed by the marketing authorisation holder to perform the activities described in Title IX. … 8. If the outcome of the inspection referred to in point (d) of paragraph 1g is that the marketing authorisation holder does not comply with the pharmacovigilance system as described in the pharmacovigilance system master file and with Title IX, the competent authority of the Member State concerned shall bring the deficiencies to the attention of the marketing authorisation holder and give him the opportunity to submit contents. In such case the Member State concerned shall inform the other Member States, the Agency and the Commission. Where appropriate, the Member State concerned shall take the necessary measures to ensure that a marketing authorisation holder is subject to effective, proportionate and dissuasive penalties. Article 111a The Commission shall adopt detailed guidelines laying down the principles applicable to inspections referred to in Article 111.”

“MHRA inspectors consider that [Roche] co-operated fully with the re-inspection conducted in October and November 2013. The re-inspection was conducted according to the inspection plan and Roche made its documentation and personnel fully available to the inspection team (at both the UK and US site).”

“I do not accept the submission that the MHRA was obliged as a matter of fairness to inform Roche in terms on, for example, 18th September 2013, that the MHRA was co-operating closely with the EMA and would provide the EMA with the Re-Inspection report (or an advance briefing note summarising the findings from the Re-Inspection), given the background knowledge and understanding of Roche in any event. Roche knew that the contents of any adverse Re-Inspection Report would reach the EMA. Roche can be taken to have understood the MHRA to be under a duty to co-operate with the EMA. The details of that co-operation were not matters that Roche was entitled to know, let alone did fairness demand that it be told.”

“The real complaint of DTF is that Milk Marque is abusing its dominant position by its selling system. This complaint, if proved, can be remedied either directly by one of the three alternative routes already mentioned, or indirectly by obtaining relief against the respondents requiring them to take appropriate steps to eliminate the Art. 86 abuse of Milk Marque. DTF has failed to explain why the indirect route [i.e. by judicial review proceedings] is more effective than the direct route. To assert, as DTF does, that its complaint is against the respondents and not against Milk Marque is merely to invite the question, Why?. In determining whether there are alternative adequate remedies, the court must look at the realities of the situation. The reality here is that the complaint is against the system being used by Milk Marque. The issues raised are ones which the European Commission and/or the MMC are well qualified to determine.”

“But that response was entirely positive from Roche’s point of view. It is difficult to see how its provision could be said to entitle Roche to any substantive relief.”

“In some cases it may not be appropriate or practicable to give notice of proposed disclosure either at all or in time to enable the owner of the documents to have an opportunity to respond. The documents may be urgently required elsewhere, or it may appear that disclosure would hamper investigations. In such a case the designated member of the SFO would not, in my judgment, be acting unfairly if he decided to go ahead without giving the sort of notice which in other circumstances would be required. But, having disclosed the documents, he would then have to consider whether the owner of the documents should be told what had taken place. It may be that he should not be told in order to protect ongoing investigations, but in my judgment the starting point should always be that the owner of the documents is entitled to be kept informed rather than the reverse. That is what, as it seems to me, fairness demands, not only because the documents are his, subject to his right to confidentiality save insofar as his rights have been curtailed by statute, but also because he cannot exercise his remaining rights in any way unless he knows what is going on. If the matter is approached in the right way it may be that in most cases, for good reason, no notice will be given. That seems to me to be immaterial. What is important is to recognise the approach that fairness demands.”

“What does fairness require in the present case? My Lords, I think it unnecessary to refer by name or to quote from, any of the often-cited authorities in which the courts have explained what is essentially an intuitive judgment. They are far too well known. From them, I derive that (1) where an Act of Parliament confers an administrative power there is a presumption that it will be exercised in a manner which is fair in all the circumstances. (2) The standards of fairness are not immutable. They may change with the passage of time, both in the general and in their application to decisions of a particular type. (3) The principles of fairness are not to be applied by rote identically in every situation. What fairness demands is dependent on the context of the decision, and this is to be taken into account in all its aspects. (4) An essential feature of the context is the statute which creates the discretion, as regards both its language and the shape of the legal and administrative system within which the decision is taken. (5) Fairness will very often require that a person who may be adversely affected by the decision will have an opportunity to make representations on his own behalf either before the decision is taken with a view to producing a favourable result; or after it is taken, with a view to procuring its modification; or both. (6) Since the person affected usually cannot make worthwhile representations without knowing what factors may weigh against his interests fairness will very often require that he is informed of the gist of the case which he has to answer.”

“138. As already stated, the question of fairness is ultimately one of fact to be decided in all the circumstances. Relevant circumstances here include the following factors: a) first, Roche is and was at all material times a highly sophisticated and resourced commercial organisation acting by personnel expert in the field of pharmacovigilance; b) secondly, a quasi-criminal infringement procedure against Roche was, to Roche’s knowledge, underway under the Penalties Regulation. The ultimate sanction in any infringement proceedings is potentially very significant. The procedure carried with it safeguards, such as the right to silence, the right against self-incrimination and the right to require a warrant. Roche was in fact of course already addressing the infringement procedure under the Penalties Regulation directly, not least because of the EMA’s Article 6(1) request of 13th June 2012 and Article 8(1) requests of 30th January 2013, 20th March 2013 and 17th October 2013. Roche responded to each of these requests, including to the request of 17th October 2013 on 22nd November 2013, that is to say actually over the period of the Re-Inspection; c) thirdly and importantly, Roche can be taken to have known of the relevant legislative background. It can be taken to have known of the MHRA’s obligations to co-operate with the EMA as referred to, for example, in the Penalties Regulation, and, for example, of the obligation on the MHRA to provide the EMA report under Article 111(8) of the 2001 Directive. Under Article 111 of the 2001 Directive the MHRA was required to co-operate with the EMA to ensure that the legal requirements governing medicinal products were complied with and required the MHRA to act in co-operation with the EMA. That co-operation was stated expressly to consist in the sharing of information with the EMA on both inspections that are planned and that have been conducted; d) fourthly, Roche can also be taken to have known of its rights under the Penalties Regulation as referred to in subsection b) above; e) fifthly, Roche was aware at all material times that the MHRA was in fact working with the EMA for the purpose of investigating deficiencies in Roche’s systems, for example from the June 2012 press release; f) sixthly, Roche can also be taken to have known of relevant guidance such as the general guidance in GVP Module III. In the introduction it is stated: “The objectives of pharmacovigilance inspections are : i) to determine that the marketing authorisation holder has personnel, systems and facilities in place to meet their pharmacovigilance obligations; ii) to identify, record and address non-compliance with may pose a risk to public health; iii) to use the inspection results as a basis for enforcement action, where considered necessary…”

“…The [inspection] results will be used to help [MAHs] improve compliance and may also be used as a basis for enforcement action…”