Genmark Pharma Ltd. v. Minister for Health [1997] IEHC 121; [1998] 3 IR 111 (11th July, 1997)

Judgment of Ms. Justice Carroll delivered on the 11th day of July, 1997. 1. This is an Application for Judicial Review by way of Certiorari quashing a decision of the Minister of State at the Department of Health dated the 20th May, 1994 under powers delegated to him by the Minister for Health, which refused an application for product authorisation for a drug known as Edelfonsine. The power was delegated under the Health (Delegation of Ministerial Function) Order, S. I. No. 62 of 1993. No point is taken in relation to this delegation. References to "the Minister" include the Minister for Health or the Minister for State (as the case may be). The Applicant, Genmark Pharma Limited ("Genmark"), also seeks declarations that the Minister failed properly to apply EC Directives 65/65 (as amended) and 75/318 (as amended) as also Statutory Instrument No. 210 of 1984, being the Medical Preparations (Licensing Advertisement and Sale) Regulations 1984. 2. EC Directive 65/65 (as amended) provided in Article 3 that no medicinal product could be placed on the market of a member state unless a marketing authorisation had been issued by the competent authority of that member State in accordance with the relevant procedures. Article 5 provided that an authorisation should be refused if (inter alia):- "After verification of the particulars and documents listed in Article 4 it proves that the proprietary medicinal product is harmful in the normal conditions of use or that its therapeutic efficacy is lacking or is insufficiently substantiated by the applicant....." 3. There is provision under Article 7 that the procedure should be completed within 120 days of the date of application. In certain circumstances this could be extended for a further 90 days. 4. Where an application is refused, Article 12 provides that the decision should be notified to the party concerned stating in detail the reasons on which it was based and at the same time the party shall be informed of the remedies available under the law in force and the time limit allowed for the exercise of those remedies. Article 21 provides that an authorisation to market a medicinal product shall not be refused, suspended or revoked except on the grounds set out in the directive. The statutory instrument implementing Directive 65/65 (as amended) is the Medical Preparations (Licensing, Advertisement and Sale) Regulations, 1984, S. I. 210 of 1984 ("the 1984 Regulations"). Under those regulations medical preparations could only be sold or manufactured if licensed for that purpose under the regulations by the Minister (Article 4). This is referred to as "product authorisation". 5. The Minister was designated the competent authority for the grant of product authorisations. Article 7 of the 1984 Regulations provides:- "(1) An application for a product authorisation shall be made to the Minister and shall be in such form and be accompanied by the appropriate charge provided for under Article 10 and by such information documents, samples and other materials as the Minister may require. (2) ...... (revoked). (3) In the examination and determination of an application for a product authorisation, the Minister shall take into consideration such criteria as appear to him to be relevant in the case of the application and, in particular, the information supplied by the applicant in relation to (a) the safety and efficacy of the medical preparation to which the application relates and the purpose for which the medical preparation is intended by the applicant to be administered, and (b) the quality of the medical preparation." 6. Article 9(1) of the 1984 Regulations provides:- " (1) The Minister may refuse an application for a product authorisation where - (a) the applicant fails to submit information, documents, samples or other materials in accordance with Article 7 (1), or (b) the Minister is satisfied, following examination of such information, documents, samples or other materials that - ........ (iii) the therapeutic efficacy of the preparation is lacking or is insufficiently substantiated by the applicant........" 7. This mirrors the provisions of Article 5 of Directive 65/65. 8. Directive 65/65 was amended by Directive 75/318 and 91/507. Among the recitals to Directive 75/318 it is stated:- "Whereas the concepts of 'harmfulness' and 'therapeutic efficacy' referred to in Article 5 of Directive 65/65 can only be examined in relation to each other and have only a relative significance depending on the progress of scientific knowledge and the use for which the (...) medicinal product is intended; whereas the particulars and documents which must accompany an application for authorisation to place a (...) medicinal product on the market demonstrate that potential risks are outweighed by the therapeutic efficacy of the product; whereas failing such demonstration the application must be rejected; whereas the evaluation of 'harmfulness' and 'therapeutic efficacy' may be modified in the light of new discoveries and standards and protocols must be amended periodically to take account of scientific progress." 9. Article 2 provides:- "Notwithstanding the provisions of other directives on (....) medicinal products, Member States shall take all appropriate measures to ensure that the competent authorities examine the particulars and documents submitted in support of applications for marketing authorisation in accordance with the criteria of the Annex to this directive." 10. Part 4 of the Annex deals with clinical documentation. 11. Part 4, Section F is headed 'Clinical Efficacy and Safety' and provides (at paragraph 1):- "(1) In general, clinical trials shall be done as 'controlled clinical trials' and if possible, randomised; any other design shall be justified. The control treatment of the trials will vary from case to case and also will depend on ethical considerations; thus it may, in some instances, be more pertinent to compare the efficacy of a new medicinal product with that of an established medicinal product of proven therapeutic value rather than with the effect of a placebo. As far as possible, and particularly in trials where the effect of the product cannot be objectively measured, steps should be taken to avoid bias, including methods of randomisation and blinding." 12. Part 4, Section G is headed 'Documentation for Applications in exceptional circumstances'. It provides that when in respect of particular therapeutic indications, the applicant can show that he is unable to provide comprehensive data on the quality, efficacy and safety under normal conditions of use because (inter alia) it would be contrary to generally accepted principles of medical ethics to collect such information, marketing authorisation might be granted subject to certain conditions. 13. The medical product concerned in this case is Edelfonsine. It is intended for use in cases of inoperable small cell lung cancer. Dr. Rabbe Nordstroem who swore the grounding affidavit says that it is an anti neoplastic agent unlike chemotherapy drugs which operate to destroy the neoplastic cells. Edelphonsine operates to induce cells to terminal proliferation or to inability to proliferate. It was invented by scientists of the Max Planck Society in Germany and a German company, Medmark Pharma GmBh. was licensed to develop and exploit the invention in 1987. 14. Genmark is an associated company of Medmark Pharma and plans to manufacture the drug in Ireland if permitted. Doctor Nordstroem sets out claims for the efficacy of the drug but the Court is not concerned with the question of efficacy. It is only concerned with the validity of the decision making process. 15. The application for product authorisation for Edelfonsine was made by Waterford Clinical Associates Limited (t.a. Shandon Clinic) on the 7th March, 1991 to the Secretary of the Department of Health. In the application form the company is stated to be the "product authorisation holder". 16. This was acknowledged on the 7th March, 1991 and the company was told that the application would be processed in consultation with the National Drugs Advisory Board ("the NDAB"). It was therefore necessary to furnish the NDAB with such information and facilities as they might require in the course of examination of the application for the purpose of advising the Minister. 17. The application comprised 45 volumes of text in German. Doctor Teeling of the NDAB wrote to Professor Cleary of Shandon Clinic on the 5th February, 1992 to say that dossier had been found to be impossible to assess and asking the company to resubmit the application taking the CPMP (Committee for Proprietary Medicinal Products) guidelines into account. He was asked if it was intended to undertake phase III clinical trials. Professor Cleary replied on the 10th February, 1992 requesting a meeting between Doctor Teeling and the Clinical Research Director of the sponsoring company. On the 11th February, 1992 Doctor Teeling said that until the dossier was in the standard form it would be impossible to assess the product and asked for an amended dossier using the standard headings outlined in the enclosed guidelines in order to proceed with assessing it. If considered necessary after initial assessment, Doctor Teeling said a meeting could be arranged. 18. Doctor Nordstroem says in his grounding affidavit that subsequent to this Genmark took over the conduct of the application. On 20th May 1992 it lodged 16 books in English. On the 21st September, 1992 Doctor Nordstroem wrote to Doctor Teeling enclosing the analysis of an ongoing clinical study with the drug and asked that marketing approval would be granted as soon as possible. 19. On the 7th April, 1993 Doctor Teeling wrote to Doctor Nordstroem in the following terms:- "Thank you for your application for product authorisation on the above product. The application has been reviewed by the Committees of the Board who have directed me to inform you that they have recommended rejection of this product on the basis of inadequate data as follows:- (1) The data on the pre-clinical studies were based on published reports from which it is impossible to extract original data or to statistically test the validity of the conclusions. Furthermore, most of these data were not relevant to the proposed indication for use claimed by the company. (2) The clinical data were found to be completely inadequate. Specifically no phase III and only two phase II open trials treating patients with non small cell lung carcinoma were submitted. The entry criteria for these studies were violated on a number of occasions and a comparison in one of the studies with historical controls was judged to be invalid and could not be used to draw any conclusions about the efficacy or safety of the product in this patient group. The Committees' recommendation for rejection of this product will now go forward to the June meeting of the National Drugs Advisory Board. I would be grateful if you could inform me within 30 days of receipt of this letter whether you wish formal rejection to take place or whether the company wishes to withdraw this product." 20. The correspondence was then taken over by Genmark's solicitors who wrote to Doctor Teeling on the 6th May, 1993 enclosing a formal response by Dr. Nordstroem dated 5th May, 1993 to the issues raised by the letter of the 7th April. The solicitors said that the response required to be considered in conjunction with the original detailed application and requested that any additional queries should be directed to them. The formal response of Doctor Nordstroem disagreed with the statement that the data was inadequate and set out reasons in an eight page letter together with enclosures. A further audit report by Professor Murphy of University College Cork dated the 5th July, 1993 was forwarded by Genmark's solicitors on the 15th July, 1993 for the attention of the members of the NDAB. 21. On the 3rd August, 1993 the acting secretary of the NDAB wrote to Genmark's solicitors to say the supplementary data had been reviewed by the Board's Committees and he was directed by the Board to inform him that it upheld its original decision to recommend the rejection of the application. 22. Genmark's solicitors replied on the 18th August, 1993 requesting the Board to indicate in detail in writing the reasons the product had been rejected. They requested that the Board would nominate some person with whom their clients could liaise for the purposes of discussing the Board's requirements. They also asked for a list of the members of the Board with details of their professional qualifications and experience in the subject area. They further asked if the Board received advise from any outside sources to confirm the position, indicating the source of that advice. 23. The acting secretary of the NDAB replied on the 20th August, 1993 saying the reasons for recommending the rejection of the application were contained in Doctor Teeling's letter to the company on the 7th April, 1993 and he enclosed a copy. He added that the company could still withdraw its application at that stage prior to formal rejection. 24. On the 24th August, 1993 Genmark's solicitors enquired from the secretary of the NDAB whether the decision could be appealed in any way and within what time frame and also asked for a reply to the letter of 18th August. The acting secretary wrote on the 6th September, 1993 to say the matter was discussed by the Committee on Drug Usage and Adverse Reactions at its meeting on the 2nd September, 1993 and it was recommended that it be brought to the Board for further consideration at its meeting on the 7th October, 1993. 25. On the 4th October, 1993 Genmark's solicitors enclosed a further document entitled "Edelfonsine - Summary", for circulation to the Board members for the meeting on the 7th October, 1993. 26. On the 15th October, 1993 the acting secretary wrote to Genmark's solicitors to say the Board had considered the additional information at its recent meeting and the application was not approved because of the absence of adequate efficacy data i.e. randomised clinical trials. He said that it was intended that the application would be formally rejected at the December meeting of the Board. Alternatively, they could withdraw the application and resubmit when appropriate efficacy data were available. 27. On the 24th November, 1993 Genmark's solicitors wrote to say their client's position and proven experience was that randomised clinical trials were neither appropriate nor permissible in the case of Edelfonsine. They enclosed a detailed memorandum explaining their client's position and containing proposals to enable the application to proceed for circulation to the Board members. On the 22nd December, 1993 Genmark's solicitors were notified by the acting secretary of the NDAB that the matter was reviewed by the Board at its meeting on the 2nd December, 1993 and it recommended the rejection of the application on grounds of inadequate evidence of efficacy. He said the Board's recommendation was being communicated to the Minister for Health. This was done by letter to the Minister dated 23rd December 1993 saying a detailed letter specifying the grounds for recommending rejection would be sent shortly. 28. Genmark's solicitors replied to the NDAB on the 6th January, 1994 and said in the circumstances they insisted on a reply to their letter of the 18th August, 1993. Genmark's solicitors wrote to the Minister for Health on the 6th January, 1994 criticising the Board's recommendation. They said the application fell to be decided by him as Minister and that in order that he might be fully briefed they enclosed a booklet of correspondence between their firm and the Board. They claimed the documentation would justify him in either granting the product authorisation or at the very least in instructing the Board to reconsider the matter in accordance with the EC legislation and guidelines. The receipt of this letter was acknowledged on 7th January, 1994. 29. On the 7th January, 1994 the secretary of the NDAB wrote to the secretary of the Department of Health concerning the application. This letter was not seen by Genmark until after discovery was made. It was in the following terms:- "The above product was recommended for rejection at the December meeting of NDAB. In arriving at this decision the Board accepted the advise of its Committees on Drug Evaluation and Toxicity and on Drug Usage and Adverse Reactions, both of which had recommended that the product application should not be approved. The reasons for rejection are as follows:- (1) The pre-clinical data submitted were inadequate. The data was based on published reports from which it is impossible to extract original data or to statistically test the validity of the conclusions. Furthermore, most of the data was not relevant to the proposed indication for use. (2) The clinical data submitted was inadequate to support the claims made for the product. (a) Pharmacokinetic data was incomplete. (b) The dose-response relationship was not satisfactorily investigated. (c) No controlled clinical trials were carried out. Only phase II open studies treating small numbers of patients with non-small cell lung cancer were submitted. Even these were flawed since the entry criteria were violated on a number of occasions, thus invalidating the results. The only comparative data submitted used historical controls (which is not acceptable) and could not be used to draw any conclusions about the efficacy of the product in this specific patient group. Furthermore, although the Applicant claimed that use of this product improved quality of life the data provided did not substantiate this claim. Similarly, data on side effects was completely inadequate to assess the safety of use of the product. (d) No randomised clinical trials (phase II or III) were submitted. In conclusion the dossier does not comply with either (i) National/EC guidelines for applications for product authorisations in respect of medicinal preparations for human use, containing novel active ingredients nor (ii) EC guideline on 'Evaluation of Anti-Cancer Medicinal Products in Man'. The product has now been formally been recommended for rejection by the National Drugs Advisory Board." 30. The matter was submitted to the Minister for decision by Minute dated 20th January, 1994. The matter was then resubmitted on 3rd February, 1994 to the Minister for State at the Department of Health to whom the power to make a decision under the regulations had been delegated. As already stated no point arises in respect of this delegation. 31. On the 23rd February, 1994 the Minister for State wrote to Waterford Clinical Associates Limited (trading as Shandon Clinic) saying:- "On the basis of the material before me including the recommendations of the National Drugs Advisory Board it would appear that you have not made out a case for the granting of a product authorisation in respect of Edelfonsine. However, I will refrain from making a decision on the matter for a period of 8 weeks from the date hereof to enable you to meet further with officials of the National Drugs Advisory Board. You should contact Mr. Cyril O'Sullivan, Chief Executive Officer of the Board.....who will arrange a meeting for you." 32. A copy of this letter was sent to the NDAB on 14th March, 1994. Genmark's solicitors replied to the letter of 23rd February, 1994 on the 9th March, 1994 saying:- "Please note that Waterford Clinical Associates Limited are no longer involved in this application which was taken over by Genmark Pharma Limited of Castletownroche, Co. Cork in May 1992. Since May 1993 all correspondence in this matter has been through this firm and we would appreciate if you would note your records accordingly." 33. They confirmed that a meeting would be arranged. 34. In writing on 24th March, 1994 to arrange the meeting, Genmark's solicitors asked the CEO of the NDAB if he would confirm that the NDAB would at least in principle be prepared to reconsider its advice to the Minister on foot of what transpired at the meeting. They also asked for copies of all communications between the NDAB and the Minister in respect of the product Edelfonsine. 35. The CEO replied on the 7th April, 1994 saying that as the Board had made its recommendation to the Minister following an exhaustive review of all data submitted, reconsideration of the advice to the Minister would not be possible. He also pointed out that correspondence between the Board and the Minister could not be provided and said they would have received any relevant correspondence in the course of the evaluation of the application. He said that in the course of the meeting they could confirm the reasons for their recommendations to the Minister. 36. On the 27th April, 1994 Genmark's solicitors wrote to the Minister for State at the Department of Health referring to the meeting between the CEO and the secretary of the NDAB and their clients on the 18th April. At the meeting the CEO of the NDAB outlined the procedures adopted in evaluating the application and making its recommendation to the Minister. He also said that correspondence between the NDAB and the Minister could not be provided and that the Minister would state the reasons for his decision when communicating his decision to Genmark. The solicitors complained there was no discussion or debate on the medicinal aspects of the application or on the ethical consideration affecting clinical trials. They said the Minister was required to consider not just the advice received but also Genmark's response thereto and it was necessary for Genmark to be appraised of all communications from the NDAB so as to enable it to put its response before the Minister. They complained Genmark had not had any opportunity of putting its case directly to the Minister. They pointed out that it appeared to Genmark that there had been a misinterpretation of the EC directives by the NDAB, specifically by indicating that they required proof of efficacy in the form of randomised phase III studies which in view of Genmark was erroneous and not in accordance with Directive 91/507. They asked the Minister to hold a formal hearing to allow Genmark to put its case and to bring evidence before the Minister of the benefits of the drug and the difficulties in obtaining phase III studies and to contest any contrary views that were advanced. They referred back to the communication with the NDAB the previous August, 1993 and complained that no one had been appointed with whom they could liaise and that they were not given information to enable them to assess the professional status and experience of the evaluators in the NDAB. They submitted that the Minister could not discharge his duties by accepting the recommendation of the NDAB without giving Genmark the opportunity of ascertaining the grounds for the recommendation and contesting the same. This could only be done by full disclosure of all communications and by holding a ministerial hearing to enable the Minister to evaluate the grounds for the recommendation of the NDAB. 37. The request for a ministerial hearing was refused by the Minister of State at the Department of Health by letter dated the 23rd May, 1994. 38. By letter of the same date addressed to Waterford Clinical Associates Limited the company was informed that the Minister for State had made an order refusing their application of the 7th March, 1991 for product authorisation and enclosing the order. The order of the Minister for State dated the 20th May, 1994 stated in the operative part as follows:- "I, William O'Dea, Minister for State at the Department of Health by virtue of the powers conferred by me by the Health (Delegation of Ministerial Functions) Order, 1993 have pursuant to Articles 9(1)(a) and 9 (1)(b)(iii) of the Medical Preparations (Licensing, Advertisement and Sale) Regulations, 1984 hereby refuse the application." 39. The affidavit grounding the statement in opposition was made by John Gillen of the Department of Health. He said that there was no application for product authorisation from Genmark. The application was made on the 7th March, 1991 by Waterford Clinical Associates Limited and the Minister's decision of the 20th May, 1994 was addressed to that company. He said the application made on the 7th March, 1991 was incomplete and did not comply with EC law. The NDAB was established by the Minister by S. I. 163 of 1966, the National Drugs Advisory Board (Establishment) Order, 1966 pursuant to powers conferred on him by the Health (Corporate Bodies) Act, 1961 . Among the functions of the Board is a general power to consider and report to the Minister on such general or particular matters in regard to drugs as he may refer to the Board for advice. In 1987, the NDAB published guidelines on behalf of the Minister in accordance with his guidelines published in August, 1984 to assist applicants for product authorisation under the 1984 regulations. They are not themselves regulations. Mr. Gillen said the Minister received from the NDAB letters dated the 23rd December, 1993 and the 7th January, 1994 and a substantial volume of documentation from Genmark's solicitors on the 7th January, 1994. He said it was following a consideration of this documentation that the Minister wrote to Waterford Clinical Associates Limited indicating the decision contemplated and providing further opportunity for contact with NDAB. 40. By letter dated the 5th July, 1995 it was confirmed to Genmark's solicitors that the documentation before the Minister were the documents set out at numbers 1 to 14 and 19 to 29 in the first schedule (first part) of the affidavit of discovery sworn by Mr. Gillen on 3rd July 1995. The documents Nos. 1-14 were basically correspondence between the NDAB and the Minister, the most important of which was the letter dated 7th January, 1994 which was not disclosed to Genmark, and correspondence between Genmark's solicitors, Waterford Clinical Associates Limited and the Minister and also four minutes to the Minister. The documents Nos. 19-29 do not appear to have any relevance in the context of this application. 1. The first point to be considered is the Minister's claim that Genmark has no standing to bring this application as it was not the company which applied for product authorisation; this was Waterford Clinical Associates Limited. The Minister says that when Genmark took over the conduct of the application it was to be assumed that it did so as agent for Waterford Clinical Associates Limited. There is no provision for the assignment of applications. When this point was raised in the Notice of Opposition, no evidence was produced concerning the relationship of Genmark with Waterford Clinical Associates Limited. 41. Genmark says it has "sufficient interest" within the meaning of Order 84 Rule 20(4). It says the NDAB were notified in 1992 that it was taking over the conduct of the application. The NDAB and the Minister corresponded with Genmark and the NDAB acknowledged receipt of an application from Genmark. 42. The first evidence on this point is the letter of the 10th February, 1992 where Dr. Leary of Waterford Clinical Associates Limited asked Dr. Teeling of the NDAB if Dr. Drehsen could visit her in order to fully identify and discuss the problems. He said she was employed "as Clinical Research Director of the sponsoring company". Dr. Teeling replied to Dr. Leary on the 11th February, 1992 refusing a meeting for the moment. The next letter is from Dr. Nordstroem on the 21st September, 1992 to Dr. Teeling on Genmark Pharma note paper headed "Our application for marketing approval of Edelfonsine from March 7th, 1991" (which was not correct). On the 7th April, 1993 Dr. Teeling wrote to Dr. Nordstroem thanking him for his application for product authorisation and saying the committees of the NDAB recommended rejection. She asked whether the company wished to withdraw the product. Following this letter correspondence was taken over by Genmark's solicitors. Ultimately, the NDAB wrote to the Genmark's solicitors on the 22nd December, 1993 to say it was recommending rejection. The solicitors then wrote directly to the Minister on the 6th January, 1994 stating Genmark applied for product authorisation on the 7th March, 1991 (which was not correct). An acknowledgement on behalf of the Minister dated the 7th January, 1994 simply repeated the same formula of words as in the solicitor's letter. When the Minister indicated what his decision was likely to be in respect of the application by Waterford Clinical Associates Limited he wrote to that company suggesting a meeting with the NDAB on the 23rd February, 1994. Genmark's solicitors replied to that letter on the 9th March, 1994 saying Waterford Clinical Associates Limited were no longer involved in the application which was taken over by Genmark in May 1992. At the meeting which took place on 18th April, 1994, Dr. Cleary of Waterford Clinical Associates Limited was present. The Minister ultimately made his decision on the 7th March, 1991 on the application made by Waterford Clinical Associates Limited which was communicated to that company on the 23rd May, 1994. 43. It is extraordinary that when the Minister raised this point, that Genmark did not immediately furnish proof by way of supplementary affidavit that Waterford Clinical Associates Limited had either transferred all their rights under the application to Genmark or that Genmark were processing the Judicial Review proceedings on its behalf. Alternatively, Waterford Clinical Associates Limited could have applied to be joined as a co-applicant. 44. The Minister claims that there is no provision for the assignment of rights under an application for product authorisation. However, in my opinion, that point does not fall to be considered here. There is no claim in the statement of grounds that Genmark are entitled to have authorisation issued to them and not to the original applicant, Waterford Clinical Associates Limited. The statement of grounds is based on the incorrect premise that the application for product authorisation was the application of Genmark. In my opinion, the only point in relation to this issue is whether Genmark have sufficient interest to prosecute the Judicial Review proceedings in respect of the decision made on the application by Waterford Clinical Associates Limited. 45. In spite of the lack of any documentary proof for Genmark's claim to be entitled to prosecute this claim, there seems to be no doubt that Waterford Clinical Associates Limited have acquiesced in Genmark's course of action, even to the extent that letters to Waterford Clinical Associates Limited from the Minister were passed to Genmark's solicitor to be replied to by them on behalf of Genmark. But it is also clear that Waterford Clinical Associates Limited have not dropped out of the picture as Dr. Cleary attended the meeting with the NDAB in April 1994. 46. While the correct approach would appear to have been to join Waterford Clinical Associates as co-applicants, it would be unreal to hold that Genmark have no standing because they have not produced direct evidence that they are acting with the approval of Waterford Clinical Associates Limited. I think the implication from the evidence that does exist must be that Waterford Clinical Associates Limited know of and acquiesce in Genmark's actions. Accordingly, even though the action is not constituted perfectly nevertheless, it seems to me, that Genmark have demonstrated sufficient interest to prosecute the Judicial Review proceedings. 2. Genmark claims that the Minister delegated his function to make a decision to the NDAB. However, the Minister points to the uncontested averment of John Gillan who says the Minister took advice from the NDAB. When he received the letter of the 7th January, 1994 with detailed advice he also had a substantial volume of documentation from Genmark's solicitor. Following consideration of this he wrote the letter of the 23rd February, 1994. The meeting envisaged in that letter took place on the 18th April, 1994. Then following further correspondence from Genmark's solicitor, further substantial documentation was considered by the Minister and he made his decision on the 7th March, 1991. 47. I am satisfied that it was the Minister who actually made the decision following consideration of all the submissions of Genmark. The fact that the Minister has never departed from the NDAB's recommendations to date is hardly surprising. The only decisions he had to make to the present, were cases where the NDAB recommended granting the approval. In other cases where refusal was going to be recommended the applicants in question withdrew their applications. Neither of these considerations go to prove that the Minister did not himself make the decision. 48. Genmark also alleges that there was an improper delegation of power in that the NDAB made regulations under the 1984 Regulations which they were not entitled to do. This allegation is not correct. The NDAB issued guidelines for applications for authorisations under the 1984 Regulations. They did not make regulations. 3. The next submission by Genmark is that the Minister was not entitled to seek advice from the NDAB as this was not provided for in the 1984 Regulations. However, the NDAB was a body set up to give advice under S. I. No. 163 of 1966 (as amended by S. I. No. 1996 of 1974) and it was proper for them to do so. An application for product authorisation for a medicinal product is by definition very technical and any Minister would require assistance to know what the salient points were. Genmark's solicitors themselves acknowledged in their letter of 27th April, 1994 that they did not dispute that the Minister was entitled to and, as a matter of common sense, ought to obtain expert advice. 4. Among the points raised by Genmark are the following:- 49. That the Respondent was in breach of natural and constitutional justice and in breach of Directive 65/65 (as amended) and the 1988 Regulations in that he: (i) failed to exercise independent judgment by getting advice from the NDAB in the form he did; (ii) failed to consider the information supplied by Genmark (contrary to Article 7(3) of the 1984 Regulations); (iii) took into account information not available to Genmark (i.e. the letter of the 7th January, 1994); (iv) failed to give detailed reasons for his decision. 50. In my opinion, while the Minister was entitled to seek advice, he was not entitled to rely on advice in the form of conclusions without reference to the basic material on which those conclusions were based. See Flanagan -v- University College Dublin 1988 I. R. 724 and Jeffs -v- New Zealand Dairy Production and Marketing Board 1967 I AC 551. 51. As the competent authority the Minister must be in a position to make his own evaluation of the advice received based on relevant documentation submitted. This he failed to do. Neither the documentation furnished by Genmark to the NDAB nor a reasonable summary of it was forwarded to the Minister. 52. The advice he received did not even deal with a major point made by Genmark relying on Directive 75/318 Annex Part 4 Sections (F) & (G), namely, that Grade III clinical trials were neither possible nor necessary. The advice did not say why the absence of Grade III trials was fatal. While the Minister would be entitled to make up his own mind on this question whether he received advice on it or not, he would nevertheless have to give reasons why he rejected Genmark's arguments. 53. It seems to me that the advice did not relate specifically to the documentation so that the Minister could evaluate the advice at the same time as he evaluated the submissions of Genmark. The Minister should have been sent whatever documentation was relevant to enable him to evaluate the advice and the submissions. (iii) Another flaw in the decision process was the failure to disclose to Genmark the letter of the 6th January, 1994 which was not just a repeat of the letter of the 7th April, 1993 sent to Genmark. The letter of the 6th January, 1994 contained additional matters e.g. there is reference to Pharmacokinetic data, dose response relationship, data on improved quality of life, data on side effects. It also says the dossier did not comply with National/EC guidelines. 54. Genmark was entitled to know what were the final grounds put forward by the NDAB so that it could respond to them before the Minister made his decision. It is not enough to say that Genmark was aware of the main ground i.e. lack of randomised Phase III clinical trials. It was entitled to be informed of all the grounds (see Geraghty -v- Minister for Local Government 1976 IR 153). (iv) Genmark also complains that the Respondent failed to give reasons for his decision. This is not just required by natural and constitutional justice but it is specifically required by Directive 65/65. Article 12 requires a refusal to be notified stating in detail the reasons on which it was based. In my opinion, it was not sufficient for the Minister just to refer to the Regulations. Article 12 requires detailed reasons to be given. The Regulations deal with generalities. The Minister's Order refers to Article 9(1)(a) and 9(1)(b)(iii). The question arises concerning Article 9(1)(a) as to what information, document, samples or other materials were required by the Minister (or NDAB) which Genmark failed to submit. In relation to the reference to Article 9(1)(b)(iii) the question arises whether the refusal was because therapeutic efficacy was lacking or whether it was insufficiently substantiated. 55. The Minister argued that because Genmark did not at any stage prior to the issue of proceedings ask the Minister to specify in more detail the reasons for his refusal, this was a factor to be taken into account in deciding whether the reasons were specifically stated (see O'Keeffe -v- An Bord Pleanala 1993 1 I. R. 39 at 76). In that case the decision in question was a decision of An Bord Pleanala on appeal granting planning permission subject to conditions. It was held that the document in question sufficiently identified the reasons by which the Board reached its decision. In my opinion, that case is not similar to the present one which requires, according to the Directive, detailed reasons which were not supplied. 56. For all these reasons it seems to me that an Order of Certiorari should issue. 5. There are other matters raised by Genmark which of themselves do not merit making an Order of Certiorari. (i) Genmark claims that the Minister did not observe the time limits laid down contrary to Article 7 of Directive 65/65 (as amended) and (ii) did not supply in his decision any information on available remedies contrary Article 12 of Directive 65/65 (as amended). (i) In relation to the time limit of 120 days (plus, in exceptional cases, 90 days) this was breached though not from the date of lodgement of the application. Even allowing for a delayed start, the procedure was not completed within the 120 days or even the extended period. However, the breach of the time limit does not give rise to a default grant of authorisation. Delay would be relevant in the context of an Application for Mandamus, but it is irrelevant in the context of an Application for Certiorari. (ii) While Article 12 of Directive 65/65 (as amended) requires that at the same time as the party is informed of the refusal, he should be informed of the remedies available under the law in force and the time limit allowed for the exercise of those remedies. The Minister claims there is no provision for an appeal against the decision of the Minister nor do the Directives require one. An application for Judicial Review is not an appeal against the order and is not a remedy of the type contemplated by Article 12. Genmark's complaint is that its solicitors asked the NDAB if its decision could be appealed and were given no information. This is irrelevant as it is not the decision of the NDAB but the decision of the Minister which is referred to in Article 12 of the Directive. Since there is no appeal against the order of the Minister, there has been no breach of the Directive. Even if Judicial Review is a remedy within the meaning of Article 12, Genmark has suffered no prejudice since it did, in fact, bring Judicial Review proceedings within the appropriate time limit. 6. Yet another ground was Genmark's claim that the Minister was in breach of natural and constitutional justice in that he failed to give an opportunity to Genmark to be heard. 57. It is abundantly clear that the Minister did not fail to give Genmark an opportunity to be heard. He received a bulky submission from Genmark's solicitors on the 6th January, 1994 enclosing documents in order that he might be fully briefed. On the 27th April, 1994 he had another letter making a variety of points on behalf of Genmark. The Minister was not obliged to direct an oral hearing, therefore, failure to hold one does not give rise to any claim. There was no attempt to close out Genmark from making any submission it wished to the Minister. There was no right, statutory or otherwise, to have an oral hearing. The refusal to allow an oral appeal was not a refusal to allow Genmark to make any points it wished to make. The decision making process was flawed because information on which the Minister reached his decision was not available to Genmark and therefore Genmark could not make submissions on that information. It was not flawed because of a general failure to give Genmark an opportunity to be heard. 7. Genmark also claims that the NDAB were in breach of natural and constitutional justice:- (i) in refusing to disclose the identity of members of its Committees; (ii) in refusing to give to Genmark the grounds for recommending rejection; (iii) in refusing to nominate a person to discuss matters with Genmark; (iv) in failing to supply details of advice and information obtained from outside sources. 58. In relation to these:- (i) The Genmark does not point to any principle which obliges the NDAB to disclose the identity of the members of the Committees and I can see no reason why it should be obliged to do so. (ii) The question of whether there was any duty at all on the NDAB to furnish to Genmark a copy of their final advice to the Minister was not canvassed in argument. Since there was clearly a duty on the Minister to disclose the advice, the question of the duty of the NDAB to furnish a copy of their advice to Genmark is moot. (iii) The NDAB were under no duty to assign a person to discuss matters with the Genmark. The Board is entitled to regulate its work as it deems proper. This does not include an obligation to provide for a meeting with a particular individual. (iv) If the NDAB had obtained outside advice and information unknown to Genmark, then Genmark would be entitled to be so informed. There is, however, no proof that the NDAB went outside the Board. Accordingly, this claim is irrelevant. 59. In the circumstances the appropriate Order is an Order of Certiorari quashing the Minister's Order of 20th May, 1994. © 1997 Irish High Court BAILII: Copyright Policy | Disclaimers | Privacy Policy | Feedback | Donate to BAILII