Roche Registration Ltd, R (on the application of) v The Secretary of State for Health

This case concerns the way in which the Secretary of State, acting by the Medicines and Healthcare Products Regulatory Agency (“the MHRA”), acquired information from the appellant (“Roche”) and passed that information to the European Medicines Agency (“the EMA”) under the EU pharmacovigilance regime which sets out a system for scrutiny for and reporting of harmful effects of drugs when administered to patients. Although the background to this appeal is the pharmacovigilance regime established by EU law, the determination of the appeal itself turns principally on the application of the obligation of fairness under English law and English law principles in relation to the grant of declaratory relief.

The proceedings relate to re-inspections carried out by the MHRA of Roche’s facilities in the United Kingdom between 29 and 31 October 2013 and on 14 November 2013 and of the facilities of an affiliate company, Genentech Inc. (“Genentech”) between 18 and 22 November 2013 in the USA (together, “the Re-Inspection”). Based on the Re-Inspection, the MHRA compiled a draft and then final Re-Inspection Report.

The information in question in these proceedings, including in the final Re-Inspection Report, has already been supplied to the EMA by the MHRA. The EMA is an EU institution and any ruling that it is acting or has acted unlawfully is a matter for determination by the EU courts rather than by a national court: see Case 314/85 Firma Foto-Frost v Haumpzollamt Lübeck-Ost [1988] 3 CMLR 57. It will be for the EMA to decide what use, if any, to make of the information supplied to it by the MHRA, in relation to the EMA’s own public health and enforcement functions under the EU pharmacovigilance regime. However, in the present proceedings Roche seeks declaratory relief regarding the lawfulness of the past conduct of the MHRA.

This court has been much assisted by the clarity with which Carr J in her judgment set out the relevant facts. The parties accepted the accuracy of the judgment in dealing with these matters, subject only to a couple of minor quibbles and an issue regarding what had been said by MHRA representatives and what Roche representatives had understood by this at the commencement of the Re-Inspection meetings in the United Kingdom and the USA. I deal with that issue below. Subject to that, I gratefully adopt the judge’s account of the relevant facts.

At paras. [2] and [4]-[10] the judge sets the scene thus:

“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 1^st October 2013 and 17^th 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 13^th December 2013) was unlawful;

f)

that the findings of the MHRA in the Re-Inspection Report are unlawful.”

Like the judge, this court made a confidentiality order in respect of certain documents before the court. It is not necessary to refer to the detailed content of those documents in this judgment.

The MHRA has the responsibility at national level for pharmacovigilance in relation not only to products authorised in the United Kingdom but also products regulated centrally by the EMA and authorised by the European Commission under the 2004 Regulation. Title IX of the 2001 Directive headed “PHARMACOVIGILANCE” provides so far as material as follows :

“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)…”

Article 19(1) of the 2004 Regulation provides :

“…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].”

Title XI of the 2001 Directive then provides :

“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.”

The object of Article 111 of the 2001 Directive is to ensure that Member States, in co-operation with the EMA, supervise compliance with pharmacovigilance obligations, including by inspections.

Since July 2012 the 2001 Directive has been implemented in the national law of the United Kingdom by the 2012 Regulations.

Regulations 210 and 211 create criminal offences in relation to breach of pharmacovigilance obligations. Part 16 then provides in material part as follows :

-(1) An inspector may inspect anything mentioned in paragraph (2)-

The things mentioned in paragraph (1) are-

- (1) If the outcome of the inspection of things referred to in regulation 327(2)(g) (powers of inspection, sampling and seizure: information and documents relating to safety etc) is that the holder of a marketing authorisation or traditional herbal registration does not comply with the pharmacovigilance system as described in the pharmacovigilance system master file, or any provision of Part 11 (pharmacovigilance), the enforcement authority must-

Thus, the Secretary of State has very broad powers to enforce or secure the enforcement of obligations under the EU medicines legislation. Specific powers are then conferred on MHRA inspectors for the purpose both of enforcing the 2012 Regulations through domestic criminal proceedings and the relevant EU legislation, including the Penalties Regulation.

The Penalties Regulation provides so far as material as follows :

“COMMISSION REGULATION (EC) No 658/2007

of 14 June 2007 concerning financial penalties for infringement of certain obligations in connection with marketing authorisations granted under Regulation (EC) No 726/2004 of the European Parliament and of the Council

…

Whereas:

…

(3)

Moreover, in view of the provision made by Article 84(1) of Regulation (EC) No 726/2004, under which the Member States are to determine the penalties to be applied for infringement of the provisions of that Regulation or the Regulations adopted pursuant to it and to take the necessary measurers for their implementation, action at Community level should be taken only in cases where the interests of the Community are involved. In that way, the effective enforcement of Regulation (EC) No 726/2004 would be ensured by an appropriate management of the resources available at Community and national level…

(6)

In order to ensure the effective conduct of the inquiry stage of alleged infringements, the Agency and Commission should have recourse to the competent authorities of the Member States, designated as the supervisory authorities of medicinal products authorised through the centralised procedure by Regulation (EC) No 726/2004, to carry out the necessary measures of inquiry and to obtain information relating to infringements falling within the scope of this Regulation…

(8)

The decision to initiate an infringement procedure under this Regulation should be taken by the Agency, which should first inform the Commission and the Member States. In the course of an inquiry, the Agency should be empowered to require such information to be supplied as is necessary to detect any infringement. It should also be able to rely on the cooperation of national competent authorities. Any supervisory powers entrusted to the Agency by Community law as regards marketing authorisations for medicinal products granted in accordance with Regulation (EC) No 726/2004 may be used by it in the course of the investigation of an infringement…

(13)

When carrying out an infringement procedure, the Agency and the Commission must ensure the respect of the rights of defence and of the principle of confidentiality in accordance with the general principle of law, and the case-law of the Court of Justice of the European Communities. In particular, the marketing authorisation holder subject to the infringement procedure should have the right to be heard by the Agency during the inquiry stage and by the Commission once it has been notified a statement of objections as well as to access the file compiled by the Agency and the Commission. While the Commission should be entitled to compel marketing authorisation holders to provide the necessary information and documents relating to a presumed infringement, the right to silence in situations where the holder would be compelled to provide answers which may involve an admission on its part of the existence of an infringement, as developed by the Court of Justice should also be respected…

CHAPTER 1

GENERAL PROVISIONS

Article 1

Subject-matter and scope

This Regulation lays down rules concerning the application of financial penalties to the holders of marketing authorisations, granted under Regulation (EC) No 726/2004, in respect of infringements of the following obligations, in cases where the infringement concerned may have significant public health implications in the Community, or where it has a Community dimension by taking place or having its effects in more than one Member State, or where interests of the Community are involved:

…

13.

recording and reporting of suspected serious adverse reactions and, in the case of veterinary medicinal products, human adverse reactions, as referred to in Article 24(1) and Article 49(1) of Regulation (EC) No 726/2004;

…

15.

detailed recording of all suspected adverse reactions and submission of such records in the form of periodic safety update reports, as referred to in Article 24(3) and Article 49(3) of Regulation (EC) No 726/2004;

16.

communication of information relating to pharmacovigilance concerns to the general public, as referred to in Article 24/5 and Article 49(5) of Regulation (EC) No 726/2004;

…

Article 3

Cooperation by the competent authorities of the

Member States

1.

The competent authorities of the Member States shall cooperate with the Agency and the Commission to enable them to carry out their duties under this Regulation.

2.

Information provided by the national competent authorities in response to a request from the Agency or the Commission under this Regulation shall be used by the Agency and the Commission only for the following purposes:

(a)

as evidence for the purposes of applying this Regulation

(b)

for carrying out the tasks entrusted to them for the authorisation and supervision of medicinal products under Regulation (EC) No 726/2004…

The infringement procedure for the purposes of the Penalties Regulation is set out in detail in Chapter II of the Regulation, entitled “Infringement Procedure”. “Infringement procedure” is not itself a defined term, but its meaning appears from the provisions of Chapter II. Recital (13) to the Regulation, set out above, indicates that it is when carrying out an infringement procedure within the meaning of the Regulation that the EMA and the Commission must ensure the respect of the rights of defence and so forth. The Recital does not refer to national competent authorities, and under the scheme of the Regulation it is the EMA and the Commission (not those authorities) which initiate and implement an infringement procedure. The Recital indicates the intention of the EU legislator that the EMA and the Commission should ensure that there is proper protection of the rights of defence of an MAH in the course of the infringement procedure, and Chapter II includes specific protections applicable in the course of the infringement procedure as against the EMA and the Commission to give effect to that objective.

Section 1 of Chapter II deals with the inquiry stage as follows. Article 5 provides for the EMA to initiate the infringement procedure. Article 6 confers a power for the EMA to request from the MAH any information relating to an alleged infringement. Article 7 states that “The [EMA] shall send written notification of the initiation of an infringement procedure to the [MAH] concerned, to the Member States and to the Commission.” Article 8, relating to requests by the EMA, is set out below. Article 9 confers a right for the MAH to be heard by way of written observations before any report under Article 10 is adopted by the EMA and provided to the Commission and others. Under Article 10(2), where the EMA considers that the MAH has committed an infringement, “the report shall also include an assessment of the circumstances of the specific case in accordance with the criteria set out in Article 18(2) and a request to the Commission for application of financial penalties.”

Article 8 provides:

Article 8

Requests by the Agency

1.

The Agency may request the marketing authorisation holder to provide written or oral explanations, or particulars or documents.

Requests shall be addressed in writing to the marketing authorisation holder. The Agency shall state the legal basis and the purpose of the request, fix a time-limit by which the information is to be provided, which shall be at least four weeks, and inform the marketing authorisation holder of the fines provided for an Article 19(1)(a) and (b) for failing to comply with the request or for supplying incorrect or misleading information.

2.

The Agency may request national competent authorities to cooperate in the investigation in the following ways:

(a)

by performing any of the tasks entrusted to the supervisory authorities by Articles 19(1) and 44(1) of Regulation (EC) No 726/2004;

(b)

by performing inspections or other supervisory measures in accordance with Articles 111 to 115 of Directive 2001/83/EC and Articles 80 81 and 82 of Directive 2001/82/EC.

Requests shall be addressed in writing and shall state the legal basis and the purpose of the request. The time limit for the submission of the reply or the conduct of the measure of inquiry shall be determined by agreement between the Agency and the national competent authority to which the request is addressed, having regard to the specific circumstances of the case.

3.

The Agency may ask any natural or legal persons to provide information relating to the alleged infringement.

Requests shall be addressed in writing and shall state the legal basis and the purpose of the request, and shall fix a time limit by which the information should be provided, which shall be at least four weeks…

Section 2 of Chapter II deals with the decision-making stage. Subsection 1 deals with procedure. Under Article 11, if, following receipt of a report from the EMA under Article 10, the Commission decides to continue with the infringement procedure it has to notify the MAH of a statement of objections setting out the allegations against it and the evidence on which the allegations are founded. Article 12 provides for the MAH to have a right to reply. Article 13 provides for the MAH to have the right to request an oral hearing. Article 15 allows for the Commission to return the case-file to the EMA for a new period of inquiry if additional information is required. Article 14 provides a power for the Commission itself to make requests for information, as follows:

Article 14

Requests for information

1.

After receipt of a request from the Agency pursuant to Article 10(2) and before adoption of the decision referred to in Article 16, the Commission may at any time request the marketing authorisation holder to provide written or oral explanations, or particulars of documents, relating to the alleged infringement.

Requests shall be addressed in writing to the marketing authorisation holder. The Commission shall state the legal basis and the purpose of the request, fix a time-limit by which the information is to be provided, which shall be at least four weeks, and inform the marketing authorisation holder of the fines provided for an Article 19(1)(c) and (d) for failing to comply with the request or for supplying incorrect or misleading information.

2.

The Commission may request the Agency, the national competent authorities or any other natural or legal persons to provide information relating to the alleged infringement.

Requests shall be addressed in writing and shall state the legal basis and the purpose of the request. Where the request is addressed to the Agency or a national competent authority, the time-limit by which the information is to be provided shall be determined by the Commission after consultation of the Agency or the national competent authority to which the request is addressed, having regard to the specific circumstances of the case. Where the request is addressed to other natural or legal persons, it shall fix a time-limit by which the information is to be provided, which shall be at least four weeks.

Subsection 2 of Section 2 deals with “Decision and financial penalties”. Article 16 provides that where the Commission finds that the MAH has committed an infringement, it may adopt a decision imposing a fine not exceeding 5% of the MAH’s Community turnover in the preceding business year. Article 17 provides that such a decision shall be based exclusively on grounds on which the MAH has been able to comment. Article 18 provides in material part as follows:

Article 18

Principles governing the application and quantification of

financial penalties

1.

In determining whether to impose a financial penalty and in determining the appropriate financial penalty, the Commission shall be guided by the principles of effectiveness, proportionality and dissuasiveness.

2.

In each case, the Commission shall take into consideration, where relevant, the following circumstances:

(a)

the seriousness and the effects of the infringement

…

(c)

on the one hand, the degree of diligence and cooperation shown by the marketing authorisation holder in the detection of the infringement and the application of corrective action, or during the course of the infringement procedure or, on the other hand, any obstruction by the marketing authorisation holder of the detection of an infringement and the conduct of an infringement procedure, or any non-compliance by the marketing authorisation holder with requests made by the Agency, the Commission or a national competent authority in application of this Regulation;

…

Section 3 of the Penalties Regulation deals with sanctions for non-cooperation. Article 19(1) provides:

Article 19

Financial penalties

1.

The Commission may by decision impose on marketing authorisation holders fines not exceeding 0.5% of their Community turnover in the preceding business year where, intentionally or negligently:

(a)

they do not comply with a measure of inquiry adopted pursuant to Article 8(1);

(b)

they supply incorrect or misleading information in response to a measure of inquiry adopted pursuant to Article 8(1);

(c)

they do not comply with a request for information pursuant to Article 14;

(d)

they supply incorrect or misleading information in response to a request for information pursuant to Article 14.

…

Chapter III of the Penalties Regulation makes provision for access to the file, confidentiality and temporal provisions. Article 21 provides for the MAH to have access to the case file containing evidence of an alleged infringement. Article 22 provides for the MAH to have the right to legal representation during the infringement procedure. Article 23 provides that an infringement procedure must be carried out subject to principles of confidentiality and professional secrecy. Articles 24 to 26 set out various time limits and limitation periods.

Where the Commission makes a decision imposing a fine, the MAH may appeal on the merits to the General Court of the EU. There is an appeal from the General Court to the Court of Justice of the European Union (“the CJEU”). If the EMA or the Commission have acted unlawfully, or if they seek to rely on evidence where to do so would breach the rights of defence of the MAH, the Charter of Fundamental Rights or any general principle of EU law, the General Court or, as the case may be, the CJEU will be in a position to grant appropriate relief.

The relevant provisions of the 2001 Directive, the 2004 Regulation and the Penalties Regulation did not change in material ways when these legislative instruments were amended in the course of 2012.

As appears from the EU legislative framework, Roche will have the benefit of full protection for its rights of defence against the EMA and the Commission in the course of the investigation procedure. There is no possibility of Roche being made subject to a fine by the Commission under the Penalties Regulation without Roche first being subject to the investigation procedure with all the procedural protections which are inherent in that procedure. Nothing done by the MHRA has deprived or could deprive Roche of this protection and the MHRA has no power itself to subject Roche to a fine under the Penalties Regulation.

The judge refers at [5] and [22] to there being three different types of investigation by the MHRA: (i) inspections following the identification by the MHRA of deficiencies, which looks at the implementation of CAPAs (i.e. under Article 111(1)(b) of the 2001 Directive); (ii) inspections requested by the CHMP, the relevant body of the EMA (i.e. under Article 111(1)(c) of the 2001 Directive); and (iii) inspections for the purposes of the Penalties Regulation (i.e. pursuant to a request under Article 8 of that Regulation). This is not an exhaustive list.

The MHRA also, of course, carries out routine inspections under Article 111(1): it was such a routine inspection which identified deficiencies on the part of Roche and led to the requirement that CAPAs be implemented, which in turn led to the Re-Inspection to see if they had been. The MHRA may carry out its own enforcement investigations where the EMA is not involved under the Penalties Regulation. In addition, although EU law does not require the introduction of criminal offences in national law to back up the pharmacovigilance regime in the Regulations and the 2001 Directive, the United Kingdom has enacted law to create such offences. This means that, as the judge mentions at [137], in some cases in the United Kingdom a full domestic law criminal investigation may take place, involving the usual protections afforded under the Police and Criminal Evidence Act 1984 (“PACE”). There was some discussion at the appeal hearing of the significance of PACE. Mr Anderson QC for Roche suggested that protections under PACE would be relevant in an enforcement investigation by the MHRA under the EU pharmacovigilance regime, whether instituted of its own motion or at the request of the EMA. However, Mr Peretz QC for the MHRA explained that PACE would only be relevant to a criminal investigation conducted for the purpose of bringing domestic law criminal proceedings.

The judge’s account of the facts continues at paras. [21]-[75]:

“21.

There are four material witness statements addressing the factual background to the claim :

a)

for Roche : from Dr Peter De Veene dated 28^th January 2014 and Mr Nicholas Phillips dated 28^th January 2014. Dr De Veene has been the qualified person for pharmacovigilance ("QPPV") of Roche since June 2011. Mr Phillips has been the head of inspections management at Roche Products Limited since 2007;

b)

for the MHRA : Dr Anya Sookoo dated 28^th February 2014 and Mr Jonathan Rowell dated 10^th April 2014. Dr Sookoo is an expert inspector in Good Clinical Practice and pharmacovigilance for the MHRA. Mr Rowell is a senior pharmacovigilance inspector for the MHRA. It was Dr Sookoo and Mr Rowell who carried out the Re-Inspection, with Mr Rowell acting as lead inspector. In a covering letter dated 28^th February 2014 the Treasury Solicitor confirmed to Roche's solicitors that Dr Sookoo's statement gave "a full and fair account of the factual background to the matters of which [Roche] complain[ed]." Documents were exhibited which it was considered, in accordance with the duty of candour, should be disclosed.

22.

As explained in paragraph 5 above, there are different types of investigation by the MHRA : inspection following the identification by the MHRA of deficiencies which looks at the implementation of CAPAs and inspections requested by the CHMP and inspections for the purpose of the Penalties Regulation. The EMA refers to the first two categories of inspection in a document titled "PROCEDURE FOR THE PREPARATION OF A RISK-BASED PROGRAMME FOR ROUTINE PHARMACOVIGILANCE INSPECTIONS OF MAHs CONNECTED WITH HUMAN CENTRALLY AUTHORISED PRODUCTS" (April 2009):

"INTRODUCTION

According to the [2004 Regulation] the supervisory authorities shall be responsible for verifying on behalf of the Community that the holder of the marketing authorization of the medicinal product for human use...satisfies the requirements laid down in Titles IV, IX and XI of [the 2001 Directive]…The Competent Authority shall ensure, by means of repeated inspections, and if necessary unannounced inspections., that the legal requirements governing medicinal products are complied with…

According to the volume 9A, the CHMP, in conjunction with the Competent Authority of the Member State in whose territory the MAH's QPPV is located and applicable Pharmacovigilance and Inspectors' Working Parties, will determine a programme for inspection in relation to centrally authorised products. The inspections will be prioritised based on the potential risk to public health, the nature of the products, extent of use, number of products that the MAH has on the EEA market and other risk factors.

Based on this, a written procedure that covers the preparation, revision, implementation and supervision of an annual inspection programme is needed…Sufficient resources must be determined and made available to ensure that the designated programme of inspections can be carried out in an appropriate manner.

In general, it is anticipated that national inspection programmes will fulfil the need for the routine inspections of this programme and therefore it is expected that the programme described in this procedure focused on CAP products will be achieved mainly through the national programmes. However, there will be situations where these inspections might be specifically requested by the CHMP (eg global PhV sites in third countries). Targeted inspections will also be reflected in this programme as they may replace the need for a routine inspection."

23.

Roche emphasises that the attitude adopted by Roche (and indeed, it is said, by the pharmaceutical industry generally) in relation to inspections arising out of CAPAs and CHMP requests is one of deferential co-operation and openness. Dr De Veene states that such inspections are regarded as routine pharmacovigilance inspections. He wishes to ensure that Roche lives up to the MHRA's expectations and to maintain a good and cordial working relationship with the inspectors. The MHRA inspectors expect a MAH to act transparently and frankly. MAHs tend to accept the inspectors' findings unquestioningly even if such findings are not based on a strict application of relevant legal requirements or guidance. Rather the focus is on CAPAs. The hope is that by acting in this way MAHs can influence the tone and perhaps even the findings of a final inspection report. As set out above, the final report is shared routinely with the EMA and other Member States.

24.

Between 16^th and 20^th January and 28^th February and 1^st March 2012 the MHRA conducted a routine inspection of Roche's headquarters in the UK. On 4^th May 2012 it sent a draft first inspection report to Roche which included three serious findings of alleged non-compliance that were classified as "critical" ("the first inspection report"). A "critical" finding is "a deficiency in pharmacovigilance systems, practices or processes that adversely affects the rights, safety or well-being of patients or that poses a potential risk to public health or that represents a serious violation of applicable legislation and guidelines" (as defined in the EMA's standard operating procedures) .

25.

Roche's non-compliance related, amongst other things, to the processing of safety data that had arisen in the context of non-interventional programmes ("NIPs"). The MHRA had particular concerns relating to a programme called "Access Solutions" which was run by Genentech. Access Solutions offered doctors and patients in the United States assistance and advice relating to insurance coverage and funding for Genentech's products which corresponded to many products marketed by the Roche group of companies in Europe. It made use of a number of service providers, including an organisation called McKesson Speciality Arizona Inc ("McKesson"). The MHRA reported that McKesson and Genentech had received reports of adverse events in relation to relevant products and had failed to pass on these reports. The MHRA took the view that this constituted a breach by Roche of its pharmacovigilance obligations under the 2004 Regulation.

26.

On 9^th May 2012 the MHRA sent the final first inspection report to the EMA. On 8^th June 2012 the Commission requested the EMA to initiate an infringement procedure under the Penalties Regulation.

27.

On 13^th June 2012 the EMA sent Roche a request for information under Article 6 of the Penalties Regulation. On 19^th June 2012 the EMA wrote to Roche with a list of questions and requests relating to improvements in Roche's pharmacovigilance system.

28.

On 21^st June 2012 the EMA issued a press release in relation to its findings of alleged non-compliance in the first inspection report. It also stated that it was working with national medicines agencies to investigate deficiencies in Roche's medicine-safety reporting system.

29.

In July 2012 the MHRA decided not to refer its findings to its Enforcement Group with a view to investigating possible criminal offences.

30.

On 19^th July 2012 the EMA wrote again to Roche requesting a comprehensive response to questions listed in an attached assessment report. On 23^rd July 2012 Roche responded to the EMA's Article 6 request of 13^th June 2012.

31.

On 23^rd October 2012 the EMA notified Roche that it was initiating an infringement procedure under the Penalties Regulation.

32.

Between November 2012 and January 2013, the MHRA assisted the EMA and co-operated with it closely in connection with the infringement procedure. It committed to support the EMA in its enforcement activities as was required of it under the Penalties Regulation and in accordance with Article 111(8) of the 2001 Directive. Thus it assisted the EMA with the drafting of a request under Article 8(1) of the Penalties Regulation and discussed with the EMA whether it should conduct a re-inspection to validate Roche's response to that request. However, the EMA in the event did not make any such request.

33.

On 19^th December 2012 the EMA sent the MHRA an Article 8(3) request to which the MHRA responded on 14^th January 2013. On 30^th January 2013 the EMA sent Roche an Article 8(1) request, to which Roche responded on 5^th April 2013, and on 20^th March 2013 a second Article 8(1) request, to which Roche responded on 18^th April 2013.

34.

On 16^th May 2013 the MHRA advised the EMA in the context of the infringement procedure, including as to the type of evidence which might be needed by the EMA and the best plan of action, including whether or not there should be a re-inspection.

35.

In the summer of 2013 James Cooke from the MHRA was seconded to the EMA to assist with the infringement procedure and in the preparation of the EMA's draft Article 10 report. As already indicated, the EMA had not carried out an infringement procedure before and did not employ its own inspectors or enforcement officers.

36.

Between May and July 2013 Roche wrote several letters to the EMA arising out of the discovery by Genentech of some 1.2 million additional records relating to Access Solutions. On 2^nd July 2013 the EMA wrote to the MHRA seeking its view on these newly discovered source documents that might contain safety data. The MHRA responded indicating that the re-inspection timetable needed to be brought forward as a result of the discovery of this new material. It wished to complete an on-site assessment of Roche's review methods. On 3^rd July 2013 Dr Williams of the MHRA put to Mr Rowell proposals for consideration of the additional records. She stated that Roche needed to be asked for more information and could be told of the plan to bring the re-inspection forward. She referred to the fact that Mr Rowell was going to speak to the EMA about the implications for the infringement notice.

37.

On 4^th July 2013 Mr Rowell responded to Dr Williams stating that the EMA was consulting with the Commission as to whether the new failures could be added as an addendum to the existing infringement procedure or whether a second infringement procedure should be started :

"…Whatever the way forward, we aim to include theses additional cases in the ongoing infringement process in some way but are seeking advice. We are considering whether the interim re-inspection needs to take place at the US site as these are largely US Programmes and we may also visit some of the vendors Roche says were holding this additional information..."

38.

Further internal MHRA communications were exchanged that day. The view was expressed by Dr Williams that because of the additional records it would not be possible to conclude in July 2013. Ideally a formal CAPA was required. Interim re-inspection might be required in the United States.

39.

On 19^th July 2013 the EMA emailed Mr Rowell. The new data would need to be considered in the framework of the public health track. It would not form part of the infringement track :

" ..As regards the re-inspection, please go ahead as you, as supervisory authority, decides is the most appropriate way forward (regardless of the ongoing infringement procedure)….Depending on the outcome of the re-inspection findings, it will be up to the [Commission] to decide on how to proceed with the re-inspection findings, if at all, during "decision making phase" in the framework of the penalties procedure."

40.

The MHRA submits that this is clear evidence that the re-inspection was not being carried out for the purpose of the infringement procedure.

41.

On 22^nd July 2013 the MHRA sent an e-mail to the EMA requesting that the EMA adopt the Re-Inspection as a CHMP request and wishing "to know the process for triggering a CHMP-requested inspection at the US (Genentech) site".

42.

On 29^th July 2013 the MHRA emailed Dr De Veene about re-inspection :

"…With the public health track coming to an end, MHRA are starting to plan for the Roche re-inspection…this will take place at some point between 18 and 29 November 2013…the re-inspection will of course focus on the Non-Interventional Programme remediation project…"

This was, from Roche's perspective, standard procedure following an inspection where the MHRA had taken the view that there were significant failings.

43.

The MHRA having set the dates for re-inspection for the end of November 2013, on 8^th August 2013 the EMA asked the MHRA for a telephone conference to discuss the re-inspection and whether the dates for such inspection could be brought forward to allow the inspection findings to be available in the context of the EMA's draft Article 10 report. The next day Mr Rowell responded, stating that that was not possible, but the MHRA could aim to provide a comment on the inspection outcome pending the final report.

44.

In mid-August 2013 the EMA sent the MHRA a draft CHMP Inspection request ahead of a telephone conference to discuss the Re-Inspection. The telephone conference took place on 15^th August 2013 with a discussion that included discussion of the timing of feedback from the Re-Inspection. A final CHMP Inspection Request was issued on 22^nd August 2013. On 29^th August 2013 the MHRA wrote to the EMA stating that it had already advanced the UK site inspection as agreed, to allow the MHRA "to provide a summary of the findings for the EMA's Infringement Regulation report to the Commission". The EMA responded stating that it would be back in touch in a fortnight "to follow up on specific questions we would like to be included in the inspection….". There was in fact no such follow up.

45.

On 30^th August 2013 the EMA sent Roche formal notification of the CHMP request for inspection, which included the CHMP IREQ ("inspection request"). The inspection request was limited to four centrally approved products, namely Avastin, Bondronat, Bonviva and Zelbora. As set out in volume 9A of the "Rules Governing Medicinal Products in the EU – Guidelines on Pharmacovigilance for Medicinal Products for Human Use" (dated September 2008) ("volume 9A"), focusing on a sample of products is a standard way of dealing with system issues.

46.

Roche states that its understanding was that the Re-Inspection was to serve the dual purposes of meeting the CHMP request and MHRA standard procedure. This was confirmed by MHRA inspectors during a telephone call prior to the Re-Inspection between Mr Phillips and Mr Rowell on 18^th September 2013. Roche's notes of that discussion read as follows:

"Scope

Although the CHMP/EMA notification referred to 4 (3) products the lead inspector clarified that the scope of the inspection will be broad and the main focus is the implementation of the CAPA.

UK : Global oversight of NIPs

US : Access Solutions and other US programs. The MHRA do not plan to visit the NIP vendor McKesson but may ask for phone interviews with selected US NIP vendors."

47.

Roche thus understood that the Re-Inspection would be broader in scope than the four listed products and would focus on CAPAs and remediation efforts since last inspection.

48.

On 1^st October 2013 the MHRA received a request from the EMA stated to be under Article 8(3) of the Penalties Regulation. It stated as follows :

"…In the framework of [the investigation] the EMA would like to seek the cooperation of the MHRA in the form of a request for information pursuant to Articles 3(1) and 8(3) of [the Penalties Regulation]…"

REQUEST FOR INFORMATION

This letter is a formal request for information made in accordance with Articles 3(1) and 8(3) of Regulation (EC) No 658/2007 which empowers the EMA to seek the cooperation of the national competent authority to enable it to carry out its duties under this Regulation and, specifically, to ask any natural or legal person to provide information relating to the alleged infringement.

The information you are requested to provide in reply of this request for information is intended to further assess the circumstances of the case in the light of the criteria set forth in Article 18(2) of Regulation (EC) No 658/2007 for the report to be established by the EMA in accordance with Article 10 of Regulation (EC) No 658/2007.

In particular you are requested to provide a response to the following questions:

Can you please confirm that your Member State has not adopted any urgent action in accordance with article 20 of Regulation (EC) No 726/2004 as a result of any of the alleged infringements set forth in the article 7 notification letter dd. 23 October 2012 (Annex I);

Can you please inform the Agency if your Member State has imposed any prior sanctions, including penalties, on the same marketing authorisation holder on the basis of the same legal grounds and the same facts by reference to the alleged infringements set forth in the article 7 notification letter dd. 23 October 2012 (Annex I).

For the purpose of the inquiry the marketing authorisation holder is identified as Roche Registration Ltd with registered office at 6 Falcon Way, Shire Park, Welwyn Garden City, AL71TW, Hertfordshire, United Kingdom, registered at the UK's company house with no. 03028626 and/or any company or entity belonging to the same mother company or group of companies as Roche Registration Ltd.

Can you please inform the Agency on the degree of diligence and cooperation shown by the marketing authorisation holder in the detection of the infringement during the MHRA inspection conducted in January and February/March of 2012, on the one hand, or on the other hand, any obstruction by the marketing authorisation holder of the detection of the infringement during the MHRA inspection conducted in January and February/March of 2012 or any non-compliance by the marketing authorisation holder with requests made by the MHRA during the inspection in January and February/March of 2012.

Can you please inform the Agency on the degree of diligence and cooperation shown by the marketing authorisation holder in the application of corrective action following the MHRA inspection conducted in January and February/March of 2012 or on any non-compliance by the marketing authorisation holder with requests made by the MHRA before, during or following the inspection in January and February/March of 2012 as well as in the context of the follow-up inspection to be undertaken by the MHRA in October/November 2013.

Please note that the information provided by the MHRA will only be used as evidence for the purpose of Regulation (EC) No 658/2007, as appropriate."

49.

It can readily be seen that these questions mirror the individual factors identified in Article 18 of the Penalties Regulation.

50.

On 17^th October 2013 the EMA sent Roche a third request under Article 8(1) of the Penalties Regulation. The EMA also sent a further request to the MHRA again expressed to be under Article 8(3):

" …

In the framework of this investigation the EMA would like to seek the cooperation of the MHRA in the form of a request for information pursuant to Articles 3(1) and 8(3) of Regulation (EC) No 658/2007.

REQUEST FOR INFORMATION

This letter is a formal request for information made in accordance with Articles 3(1) and 8(3) of Regulation (EC) No 658/2007 which empowers the EMA to seek the cooperation of the national competent authority to enable it to carry out its duties under this Regulation and, specifically, to ask any natural or legal person to provide information relating to the alleged infringement.

The information you are requested to provide in reply of this request for information is intended to further assess the circumstances of the case in the light of the criteria set forth in Article 18(2) of Regulation (EC) No 658/2007 for the report to be established by the EMA in accordance with Article 10 of Regulation (EC) No 658/2007.

We would like to request the MHRA to provide the following documents in relation to the Pharmacovigilance (PhV) inspection, which has been requested by CHMP on 22 August 2013 and that the MHRA will conduct at Roche's premises in the UK and the USA in October/November 2013:

Preliminary PhV Inspection Report;

Responses received from Roche on the above mentioned report

Final PhV Inspection Report

Please note that the information provided by the MHRA will only be used as evidence for the purpose of Regulation (EC) No 658/2007, as appropriate."

51.

The email covering this request stated that the information was "intended to establish whether certain provisions of [the Penalties Regulation] have been infringed by Roche and to assess the circumstances of the case in the light of the criteria set forth in Article 18(2) of [the Penalties Regulation]. Please note that the information provided will only be used as evidence for the purpose of the [Penalties Regulation]."

52.

An internal MHRA email to the Divisional Director stated : "Don't worry about this. This would be something we would do as standard with a CHMP requested inspection".

53.

The MHRA responded in part to the Article 8(3) request of 1^st October 2013 on 18^th October 2013. In summary, the MHRA had not taken action to suspend Roche medicinal products; no sanctions had been imposed by the MHRA on Roche; Roche had co-operated fully with the inspections in 2012, and had been co-operative during the subsequent public health investigation. Roche had responded to all information requests as far as was possible from available data. The MHRA stated that it would respond to additional questions following the Re-Inspection.

54.

As set out above, the Re-Inspection of Roche in the United Kingdom took place at the end of October and on 14^th November 2013 (and so was brought forward as the EMA had requested). Re-Inspection at Genentech took place between 18^th and 22^nd November 2013.

55.

At the time of the Re-Inspection, as set out in the witness statements of Mr Phillips and Dr De Veene, Roche did not know that the EMA had made Article 8(3) requests of the MHRA.

56.

There was reference to the infringement proceedings in the opening meetings. There is a document prepared by Mr Phillips dated 29^th October 2013 headed "Daily/Periodic Inspection Debrief". The inspection scope is described as "Implementation of CAPA from MHRA PV Inspection 2012". In the executive summary the following entry appears :

"The lead inspector confirmed that this is a re-inspection due to the critical findings noted from the 2012 PV inspection. CHMP also requested an inspection to verify the extent of CAPA fulfilment. Inspection report will be shared with the member states and EMA. Aspects of the inspection report will be used for the infringement procedure but this is not the primary purpose why they are here."

57.

Scribe notes for the 29^th October 2013 opening session are also available. The following opening exchange is recorded :

"[Mr Rowell] – Scope – Recap on previous interaction and inspection feedback will distribute to EMA as routine information sharing. Report will also be shared with FDA. CAPA status check; NIP data collection progress; new regulation activities; formal response will be provided after the second visit at USA. Preliminary feedback will be provided at the end of the UK visit.

[Mr Phillips] – Infringement procedure clarification with regards to findings from MHRA from this Inspection.

[Dr Sookoo] – We will just feed into the current infringement process…"

58.

Mr Phillips' manuscript notes of the meeting refer to Dr Sookoo stating that the MHRA re-inspection "may" feed into the infringement process. He went on to note the inspectors stating that "parallel action could be taken but would muddy the waters". Mr Phillips states that when told that aspects of the inspection report would be used for the infringement procedure, he thought this was "almost as an aside". It is nevertheless common ground that it was said in terms that the MHRA would (or at the very least might) feed into the infringement process.

59.

In response to the letter before action the Treasury Solicitor stated by letter dated 27^th January 2014:

"…the MHRA made it clear to Roche at the start of the re-inspection that the re-inspection was for standard pharmacovigilance purposes. Although Jonathan Rowell, MHRA lead inspector, cannot remember the conversation verbatim, he is clear that he did not suggest that the re-inspection was in any part being carried out for the purposes of the infringement procedure under the Penalties Regulation…"

60.

Roche states that it believed that the Re-Inspection was a normal routine inspection. As a result, according to Mr Philips and Dr De Veene, no special precautions were taken to protect Roche's position.

61.

A similar position existed at the opening of the Re-Inspection at Genentech on 18^th November 2013. Mr Phillip's executive summary of the opening meeting in the inspection debrief stated:

"The lead inspector confirmed the inspection scope, and that it is to follow-up on the non-compliances noted from 2012 PV inspection, focusing on [NIPs] and a review of the Access Solution program. It is also request by the EMA to verify the extent of CAPA fulfilment. Inspection report will be shared with the member states and EMA and the FDA. The inspection is to follow-up on the public health track and the impact assessment submitted to PRAC and to ensure that the activities implemented by Roche/GNE are comprehensive. Aspects of the inspection report will be used for the infringement procedure…"

62.

The scribe notes for 18^th November 2013 read as follows:

"[Mr Rowell] EMA request CAPA follow-up and how CAPAs were addressed by Roche. Inspection report will be shared with FDA…Inspector's interest in an "open dialogue" is mentioned by [Mr Rowell]…Wishes to follow up on "public health track". PRAC wishes to obtain information about NIPs managed by Roche to ensure activities we committed to were addressed comprehensively. Inspectors will share report with EMA/PRAC. EMA may use report for infringement procedure (NB : not further specified how exactly this would be done)."

(According to Mr Phillips, the last comment in brackets was made by the scribe because of the lack of clarity from the inspectors as to how information gathered in the re-inspection was to be used. It does not appear that the inspectors were pressed for any further clarification.)

63.

On 19^th November 2013 the EMA issued a press release stating that no new safety concerns were identified in relation to the first inspection report.

64.

On 22^nd November 2013 Roche responded to the EMA's Article 8(1) request of 17^th October 2013.

65.

On 27^th November 2013 Mr Rowell sent a "briefing note" to the EMA, including to the EMA's legal services, setting out the findings of the Re-Inspection. It recorded two critical, two major and at least 2 minor findings. It went on to make proposals for consideration by the EMA and PRAC for a proportionate approach to inspection and reporting of additional safety data.

66.

On 2^nd December 2013 Mr Rowell circulated a draft Re-Inspection Report internally for peer review, stating that he needed to get it out to Roche as soon as possible "so that the EMA can append it to their report to the Commission".

67.

On 3^rd December 2013 Dr Sookoo reviewed the draft stating:

"Given that the report is so important for the Infringement Regulation case, I am going to spend most of the day (and possibly the night) reviewing the report…"

She stated that she had tried to address some of the lawyers' comments, but that Mr Rowell might wish to think about how to "stress certain points". In her witness statement Dr Sookoo states that, amongst other things, she bore in mind making the draft clear to all readers, including the EMA's legal team who were not pharmacovigilance specialists. She wanted to ensure that the findings were communicated clearly. There was no resulting change to the nature or grading of the findings or any other fundamental change.

68.

Dr Sookoo also, on 5^th December 2013, informally reviewed parts of the EMA's draft Article 10 report.

69.

On 8^th December 2013 the MHRA sent the initial Re-Inspection Report ("the Re-Inspection Report") to the EMA, before sending it to Roche on 9^th December 2013. The draft report is confidential. But it can be said that it made critical findings of Roche. Roche made comments on 17^th January and 7^th March 2014.

70.

On 13^th December 2013 the MHRA provided the balance of its response to the EMA's Article 8(3) request of 1^st October 2013. It stated that Roche had made its personnel and documents fully available at the Re-Inspection. The MHRA considered that Roche had co-operated fully. But Roche had not been fully diligent in the application of the agreed CAPAs. Examples were given.

71.

On 20^th December 2013 the EMA sent its draft Article 10 report to Roche. It was critical of Roche. Roche submitted its comments on the draft Article 10 report on 14^th February 2014.

72.

On 19^th March 2014 the MHRA sent its final Re-Inspection Report to the EMA ("the final Re-Inspection Report").

73.

On 3^rd April 2014 the EMA sent Roche the final Re-Inspection Report.

74.

On 14^th April 2014 the EMA announced that it had concluded its inquiry and sent its Article 10 report ("the Article 10 report") to Roche, to the Member States and to the Commission for its consideration.

75.

Before leaving the facts, Roche sounds a general note of concern as to the approach adopted to disclosure by the MHRA and the EMA. It says that the full extent of co-operation between the MHRA and the EMA as set out above has only emerged as a result of repeated document requests and of the MHRA's acknowledgement of its duty of candour. But it is right to record that, for example, only a summary has been given of (and not all documents relating to) the various interactions between the EMA and the MHRA relating to Roche in 2013.”

Standing back from the detail, the following are salient features in this case: (i) Roche knew from the MHRA’s routine inspection in early 2012 that three serious or “critical” findings had been made against it in relation to compliance with the EU pharmacovigilance regime and knew that the Re-Inspection related to these matters and the corrective action it had been told to take; (ii) on 23 October 2012 the EMA gave formal notification to Roche under Article 7 of the Penalties Regulation that Roche was the subject of an infringement procedure under that Regulation in respect of those matters; (iii) on 22 August 2013, as Roche was aware, the CHMP itself requested the MHRA under Article 111(1)(c) to carry out the Re-Inspection; (iv) the scope of the Re-Inspection was determined solely by reference to what was needed for the MHRA to examine Roche’s implementation of the CAPAs and not by any request from the EMA for additional information; (v) Roche was on notice from the terms of Article 111 of the 2001 Directive, from published EMA guidance and from published Commission guidance that the MHRA was bound to share information from the Re-Inspection with the EMA and that such information could provide a basis for enforcement action under the Penalties Regulation; (vi) Roche knew, from the terms of Article 18(2) of the Penalties Regulation, that questions of diligence in implementation of corrective action in the form of implementation of the CAPAs would be relevant to the questions whether a penalty would be imposed under that Regulation and in what amount; and (vii) at the opening of the Re-Inspection meetings in both the United Kingdom and the USA, both attended by Mr De Veene and Mr Phillips for Roche, there was explicit mention by MHRA representatives that information from the Re-Inspection would be sent to the EMA who might use it in the ongoing infringement procedure under the Penalties Regulation.

This is not a promising factual basis for Roche on which to allege material unfairness by the MHRA in the way it conducted the Re-Inspection. However, Roche contends that there was unlawful unfairness on the part of the MHRA because it did not inform Roche at the time of the Re-Inspection that it had received the Article 8(3) requests of 1 and 17 October 2013 from the EMA and had been co-operating with the EMA in formulating those requests and in bringing forward the timing of the Re-Inspection to assist the EMA in the conduct of the infringement procedure.

As to the EMA guidance and Commission guidance referred to in point (v) above, Mr Anderson submitted that both sets of guidance should be read as restricted to using information from an inspection or re-inspection as a basis for the commencement of infringement proceedings, but not as evidence which could be used in the course of infringement proceedings as a basis for enforcement action. The judge rightly rejected this submission at [138]. In my view, the guidance makes it clear in each case that information from an inspection or re-inspection may be used for the purposes of enforcement action in the course of infringement proceedings, whether those proceedings are already on foot or yet to be commenced. The language used (“a basis for enforcement action”) is wider than the meaning suggested for it by Mr Anderson (whose suggestion was that it should be read, in effect, to say “a basis for the commencement of infringement proceedings”). The language used is apt to cover enforcement action sought to be taken at any stage, including in the course of infringement proceedings already on foot. There is good reason to think this is the true meaning. It makes no sense to draw the distinction proposed by Mr Anderson: the public interest in the EMA and the Commission being in a position to rely on such materials coming to them under Article 111 of the 2001 Directive may be as strong where infringement proceedings are already on foot and the evidence is relevant to those proceedings as it is where the information provided is what triggers the commencement of infringement proceedings in the first place. In both cases, it is very difficult to see why the relevant regulator in the highly sensitive field of human safety in relation to use of medicines should be precluded from making use of relevant information with which it has been provided. Moreover, Article 18(2)(c) of the Penalties Regulation makes it clear that information arising from an inspection or from a re-inspection may be highly relevant to the application and quantification of financial penalties (that is to say, enforcement action) under the infringement procedure, and again, against that background, it would make no sense to interpret the guidance so as not to cover use of information derived from an inspection or re-inspection for Article 18 purposes in the context of an infringement procedure which is already on foot.

In any event, of greater importance than the EMA guidance and Commission guidance for the purposes of the judge’s analysis and the analysis below regarding the application of the MHRA’s duty to act fairly is what can reasonably be expected to happen in light of the applicable legislative framework, in particular from the application of the duty of co-operation under Article 111 of the 2001 Directive and from Article 18(2) of the Penalties Regulation. I address this below.

As to point (vi) above, Mr Anderson emphasised that neither Mr De Veene nor Mr Phillips are lawyers. In consequence, he said, they could not reasonably be expected to pick up and understand the significance of what they were being told at the Re-Inspection meetings; nor did any lawyer attend these meetings on behalf of Roche. Against this, however, Mr Peretz submitted that neither Mr De Veene nor Mr Phillips could be regarded as ingénus in the field of pharmacovigilance. On the contrary, Mr De Veene has been Roche’s officially designated QPPV for the purposes of the European pharmacovigilance regime since June 2011, and before that was the deputy QPPV and head of the QPPV office from June 2008. In that capacity Mr De Veene has been responsible for establishing and maintaining Roche’s pharmacovigilance system and acts as the primary point of contact for EU and national regulatory authorities in relation to pharmacovigilance-related matters. Mr Phillips has been Head of Inspections Management at Roche since 2007, with responsibility for coordinating and overseeing pharmacovigilance inspections globally.

It does rather strain credulity that persons as experienced in operating with the pharmacovigilance regime as Mr De Veene and Mr Phillips for a company as large and professionally organised as Roche would be as ignorant of the legislative framework as Mr Anderson appeared to suggest they were. They did not themselves, in their evidence, hold themselves out as being ignorant of that framework. They did not say that they understood the EMA guidance and Commission guidance as bearing anything other than its natural meaning as set out above. Moreover, Mr Phillips’ own manuscript notes from the introductory meeting for the Re-Inspection in the United Kingdom on 29 October 2013 include as one of five items under the heading “Introduction” a note of the point that the re-inspection could be relevant to the existing infringement procedure, as material which could feed into that process. It does not appear to have been a matter which went over his head or which was of no interest to him. I think the judge was plainly entitled to find on the evidence before her that Mr De Veene and Mr Phillips “knew, not least because they were told in terms, that the Re-Inspection report would (or at the very least might) be fed into the infringement procedure …” ([150]).

Mr Anderson submitted that this court should be prepared to make its own assessment of the facts in relation to this, since all the evidential material available before the judge was equally available before us. The judge had heard no oral evidence.

However, an appeal will only be allowed where the decision of the lower court was “wrong” or was “unjust because of a serious procedural or other irregularity in the proceedings of the lower court”: CPR Part 52.11(3). The latter part of the Rule is not relevant here. In accordance with the usual position under CPR Part 52.11(1), the appeal is limited to a review of the decision of the lower court; there is no good reason to go further and hold a re-hearing. On the material available to us and to the judge, it cannot be said that the judge was “wrong” in relation to her assessment of the relevant facts. It is not sufficient that this court might have reached a different view of the facts if it had started from scratch or had decided to hold a re-hearing. As it happens, however, I agree with the judge’s assessment of the facts on this point and generally.

Having made these points, however, it would not be right to give undue weight to them in the overall context of the case. The main foundation for the judge’s rejection of the claim under each Ground was an appreciation of the legislative framework and of the respective roles of the MHRA, the EMA and the Commission within that framework.

After setting out the facts, the judge dealt with various jurisdictional questions: [76]-[96]. The EMA, as an Interested Party, submitted that the English court had no jurisdiction to entertain any part of the claim. Roche and the MHRA adopted more nuanced positions, which in the end came to much the same thing and was accepted by the judge: the court had formal jurisdiction to consider matters raised, but questions as to how it should exercise its jurisdiction remained to be answered in relation to the substantive claims. The EMA does not appear on this appeal to contest any of this. None of the grounds of appeal nor the respondent’s notice relate to this part of the judgment.

In the next section of the judgment, the judge addressed the substantive claim under each Ground in turn: Ground 1, concerning the significance of the reliance by the EMA upon Article 8(3) of the Penalties Regulation in making its requests to the MHRA of 1 October and 17 October 2013 for information and the request by Roche for a reference to the CJEU under Article 267 TFEU in relation to this (“the Article 8(3) issue”), at paras. [97]-[113]; Ground 2, concerning the duty of the MHRA under English public law to act fairly (“the fairness issue”), at paras. [114]-[153]; and Ground 3, concerning alleged errors of law in the Re-Inspection Report and the request by Roche for a further reference to the CJEU in relation to this (“the errors of law point”), at paras. [154]-[184].

Under Ground 1, in respect of the Article 8(3) issue, Roche argued that the EMA had no power under Article 8(3) of the Penalties Regulation to make a request for information to be provided by a national competent authority such as the MHRA. Roche says that Article 8 has a clear structure: Article 8(1) governs requests by the EMA for information from the MAH itself; Article 8(2) governs requests made by the EMA directed to a national competent authority; and Article 8(3) is limited to requests made by the EMA directed to anyone else. In this case, for its requests dated 1 and 17 October 2013 to the MHRA, the EMA relied upon Article 8(3); but, on Roche’s argument, the EMA had no power under that provision to make such a request. Therefore, Roche submitted, the MHRA had no power to provide the information it did in response to those requests, and the court should so declare. The MHRA, on the other hand, contended that Article 8(2) is not the sole and exhaustive power within Article 8 for the EMA to request information from a national competent authority, and that on its clear wording Article 8(3) also confers on the EMA power to request a national competent authority to provide it with information and so was properly and lawfully invoked by the EMA in its requests to the MHRA.

The judge held that Roche’s proposed interpretation of Article 8 is properly arguable ([102]), with the result that, according to the principle in Foto-Frost, the court would have had to make a reference to the CJEU if a determination on the proper effect of Article 8 were necessary in order for the claim in the national court to be resolved: [103] et seq. Accordingly, Roche’s request for a reference to the CJEU could not be dismissed on the basis that its contention regarding the proper interpretation of Article 8 was unarguable. On this appeal, the MHRA by its respondent’s notice takes issue with the judgment on this point.

However, the judge held that it would not be appropriate to make a reference because, as was common ground, a court should not grant relief in relation to an error of law where such error is immaterial to the decision complained of. That was the position here, since the MHRA was obliged to pass all the information it did to the EMA under its general obligations of co-operation with the EMA under Article 111 of the 2001 Directive and Article 3(1) of the Penalties Regulation: [109]-[113]. The judge rejected the suggestion that the issuing by the EMA of requests under Article 8(3) could overtake or eclipse these general obligations. There were also public interest considerations which militated against the making of a reference, including that it would be directed primarily to the lawfulness of the actions of the EMA and it would be undesirable to pre-empt the acts of an EU institution and to anticipate the arguments on the substance of the case ([112] and [182]).

The judge noted at [110] that the only possible exception, where material was supplied by the MHRA which may not have been covered by the general obligation of co-operation under Article 111 of the 2001 Directive, was information contained in two sentences in the MHRA’s letter to the EMA dated 13 December 2013. The sentences stated:

“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).”

Those sentences were part of the MHRA’s letter in response to the request by the EMA in its Article 8(3) request of 1 October 2013, in which the EMA asked the MHRA to inform it “on the degree of diligence and cooperation” shown by Roche in relation to the implementation of the CAPAs arising out of the inspection in early 2012 and of any non-compliance by Roche in respect of requests made by the MHRA in relation to that inspection and the Re-Inspection.

As the judge observed at [110], that part of the MHRA’s response, regarding co-operation by Roche, was positive from Roche’s point of view and she rejected the contention that it would be appropriate to grant any substantive relief by reason of this.

As to Ground 2 (the fairness point), it was common ground between the parties that this should be addressed on the basis of the domestic public law duty to act fairly. The judge rejected Roche’s claim that the MHRA had acted unfairly: [117]-[153]. At [138], set out below, the judge explained the significant aspects of the factual and legal context which led to her conclusion. She also reviewed the evidence in detail and found that the MHRA’s purpose in carrying out the Re-Inspection was to comply with its public health obligations under the 2001 Directive and the 2004 Regulation, and that the scope of the investigation and questions in the Re-Inspection were determined accordingly. The Article 8(3) requests “did not affect the scope or purpose of the Re-Inspection” ([140]). Sharing the inspection report with the EMA would be routine, in line with standard practice; and, indeed, as with all CHMP-requested inspections, Roche paid the inspection fee to the EMA, not the MHRA ([140]). Further, “The question of diligence on the part of Roche was always at the heart of the CAPA investigation and the Re-Inspection” ([141]); and at [144] she said:

“I do not accept the submission that the MHRA was obliged as a matter of fairness to inform Roche in terms on, for example, 18^th 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.”

At [145]-[146] the judge referred again to Roche’s general background knowledge and understanding, adding that if more were needed and that background knowledge was not enough to answer Roche’s fairness point (as the judge clearly thought it was), it was also relevant that Roche was told in terms at the commencement of the Re-Inspection meetings in the United Kingdom and the USA “that the Re-Inspection results would (or at the very least might) feed in to the infringement procedure” (a point she again referred to at [150] and [152]). Although Mr De Veene and Mr Phillips gave evidence of their surprise when they discovered the full facts of engagement between the MHRA and the EMA and said they believed they would have behaved differently if given more information by the MHRA about that engagement, the judge observed that “their beliefs do not determine the question of whether the MHRA treated Roche fairly”, and “Given the relevant background, coupled with what Roche was actually told in opening session, it cannot be said that the MHRA unfairly took advantage of Roche or in some way abused the inspection process as Roche suggests” ([150]).

At [151] the judge noted that Roche did not give particularised details about information which it would have withheld from the MHRA if told about the extent of engagement between the MHRA and the EMA, and observed that Roche would have the opportunity in the context of the infringement procedure to advance all its arguments as to whether it was impermissible for the EMA or the Commission to rely on any part of the information provided by the MHRA.

The judge then turned to consider Ground 3 (the errors of law point). Two alleged errors of law were in issue. The first was whether Roche as MAH was properly to be treated as responsible under the EU regime in respect of information regarding things done by Genentech (at the suggestion of the parties the judge called this the “MAH identity point”, but a more accurate label is “the MAH responsibility point”). At points in the final Re-Inspection Report the MHRA referred to things done by “Roche/Genentech” and referred to deficiencies in pharmacovigilance information which had been gathered by Genentech in the USA in the database for the Access Solutions Patient Support Programme. The second was whether the MHRA had inappropriately made criticisms of Roche retrospectively by reference to the more stringent pharmacovigilance obligations introduced in 2012 which were referred to at certain points in the final Re-Inspection Report (“the retrospectivity point”).

Before the judge the MHRA accepted that the extent of an MAH’s pharmacovigilance obligations under EU law for the purposes of the MAH responsibility point is an arguable issue which is not acte clair: [155]-[160]. The judge also found the retrospectivity point to be properly arguable ([168]) and regarded it as material, in the sense that it was arguably capable of making a difference to what the MHRA set out in the draft and final Re-Inspection report ([167]).

However, the judge declined to make a reference to the CJEU: [169]-[184]. This was because she considered that for the national court to proceed to grant declaratory relief would be contrary to a principle which she derived from the judgment of the ECJ in Case C-344/98 Masterfoods Ltd v HB Ice Cream Ltd [2000] ECR I-11369, that national courts should endeavour to avoid a risk of reaching conclusions inconsistent with those reached by the Commission or by the EU courts. Any ruling by the English court would not bind the Commission: see the judgment in Masterfoods at para. 48. Rather, the lawfulness of the Commission’s actions could be the subject of proceedings in the EU General Court and the CJEU. It would be undesirable to pre-empt the acts of an EU institution and to anticipate the arguments on the substance of the case; and it would be desirable not to confuse different administrative and judicial procedural powers and not to act incompatibly in connection with the division of powers: [182]. In the judge’s view, “it would be wrong in principle for this Court to pre-empt the decision of the Commission (and ultimately of the General Court on any appeal and thereafter the CJEU if necessary) either by way of substantive ruling or the making of a reference”: [183]. The judge noted that Roche still has a full opportunity to advance its case on these issues in the infringement procedure and any EU court proceedings following from that procedure and stated, “The appropriate forum and course is for Roche to maintain these arguments before the Commission, as it sees fit, and thereafter to pursue any appeal that it needs or wishes to”: [183]. Particularly given the public health and safety context, the judge considered that the public interest was “heavily in favour of allowing the regulatory proceedings to take their normal passage as swiftly as possible, without external interference or delay”: [183].