Hospira Pty Ltd and Minister for Health

Case •

[2017] AATA 2719

•

20 June 2017

Hospira Pty Ltd and Minister for Health [2017] AATA 2719 (20 June 2017)

Division:GENERAL DIVISION

File Number:           2016/0776

Re:Hospira Pty Ltd

APPLICANT

AndMinister for Health

RESPONDENT

AndJanssen-Cilag Pty Ltd

OTHER PARTY No 1

AndPfizer Australia Pty Ltd

OTHER PARTY No 2

REASONS FOR DECISION

Tribunal:Miss E A Shanahan, Member

Date of decision:                   20 June 2017

Date of written reasons:        18 December 2017

Place:Melbourne

On 20 June 2017 the Tribunal handed down an Oral Decision setting aside the decision and remitting the matter to the Minister for Health for reconsideration in accordance with the reasons now provided.

...............[sgd].........................................................

Miss E A Shanahan, Member

HEALTH – registration of therapeutic goods – biological medicines – adopted international guidelines – assessment of biosimilar criteria of internationally approved biologicals – question as to whether approval of registration is inseparable from approval of the product information – review of product information sought – product information amended by authorised review officer – statutory interpretation in relation to the power to amend product information in accordance with ss 25 and 25AA – object of the Act to ensure quality, safety and efficacy of therapeutic goods – decision set aside and remitted for reconsideration

Legislation

Administrative Appeals Tribunal Act 1975; ss 35, 37
Therapeutic Goods Act 1989; ss 4, 7D, 9D, 23, 25, 25AA, 25AB, 60, 60A
Therapeutic Goods Amendment (2013 Measures No 1) Act 2014; Sch 5
Therapeutic Goods Amendment (2013 Measures No 1) Bill 2013

Cases

Project Blue Sky Inc and Others v Australian Broadcasting Authority (1998) 194 CLR 355

Re Pfizer Pty Ltd & Department of Health, Housing and Community Services (1993) 30 ALD 647

Sanofi-Aventis Australia Pty Ltd v Apotex Pty Ltd (No 4) (2011) 202 FCR 56

Secondary Materials
Explanatory Memorandum to the Therapeutic Goods Amendment (2013 Measures No 1) Bill 2013
Oxford Encyclopaedic English Dictionary (1991)

Macquarie Concise Dictionary (5th Ed, 2009)

REASONS FOR DECISION

Miss E A Shanahan, Member

18 December 2017

  1. On 11 February 2016 Hospira Pty Ltd (Hospira) lodged an application for review by the Administrative Appeals Tribunal of the decision of a delegate of the Minister for Health (the Minister) dated 15 January 2016. The delegate (Dr McEwen) had set aside the primary determination of the departmental decision-maker (Dr Mackay) on the application of Janssen-Cilag Pty Ltd (Janssen) (1st Other Party), Janssen having, as provided by s 60(2) of the Therapeutic Goods Act 1989 (the Act), requested that several amendments be made to Hospira’s Product Information (PI) document. Dr Mackay had made two decisions, being: 1) to register Hospira’s therapeutic good, Inflectra, on the Australian Register of Therapeutic Goods; and 2) to approve a product information statement for Inflectra. Janssen had applied for internal review relating to the approval of the PI, not the decision to register Inflectra.

  2. While 24 amendments were sought, the majority had no or little impact on the eligibility for registration or the scientific content and veracity of the PI. Hospira’s application for review by this Tribunal relates to three of these amendments.

  3. While the application for review by the Administrative Appeals Tribunal had been afoot for nearly 18 months, it was not until 15 June 2017 that the parties raised the question of the legal construction of, primarily, s 25AA of the Act and the possibility that the delegate of the Minister who made the reviewable decision had exceeded the powers vested in him by the Act in amending the PI of the sponsor Hospira. 

  4. A directions hearing was held on 16 June 2017. The Applicant, Hospira, the Respondent Minister and the 2nd Other Party, Pfizer Australia Pty Ltd (Pfizer) requested that the legal construction question be heard and, if possible, determined before proceeding to the substantive issue. They also requested that the only evidence to be called would be that of Dr Mackay, the primary decision‑maker, should the Tribunal decide it would be advantageous to do so.

  5. While counsel for the Minister had raised the legal construction question, Pfizer and Hospira both agreed that the reviewable decision made by Dr McEwen on 15 January 2016 could be ultra vires. Janssen opposed the request, submitting that the Tribunal should proceed to hear the substantive issue. Each party supplied short written submissions for the Tribunal’s consideration. The Tribunal was persuaded by argument to address the legal question first and elected to wait until such arguments had been heard before deciding whether Dr Mackay’s evidence would be of assistance.

  6. The hearing took place over two days, 19 and 20 June 2017. Mr Jeremy Kirk SC with Mr Henry El-Hage of counsel, instructed by Mr Jonathan Kelp of Minter Ellison, appeared for Hospira and Pfizer. Mr Jason Pizer QC with Ms Kathleen Foley of counsel instructed by Mr Kenneth Teoh of the Therapeutic Goods Administration (TGA) appeared for the Minister. Mr Stephen Free of counsel instructed by Ms Sheena McKie of Clayton Utz appeared for Janssen. In accordance with s 37 of the Administrative Appeals Tribunal Act 1975 (the AAT Act) the Minister had lodged the required T-documents of which there were 20 volumes, totalling over 7,500 pages. These were tendered into evidence (Exhibit R1). The Minister also provided the affidavit of Dr Kerri Mackay dated 6 June 2017 (Exhibit R2). Janssen tendered the PI document as approved by Dr McEwen (Exhibit OP1).

  7. By consent of the parties, Confidentiality Orders (in accordance with s 35 of the AAT Act) have been made in relation to many entries in the T-documents and the evidence of Dr Mackay as recorded in the transcript of the hearing. The Confidentiality Orders were issued on the basis that these sections of the documents and the evidence contained commercially sensitive information.

    BACKGROUND TO THE APPLICATION

  8. While not necessary in relation to the decision made on the question of statutory interpretation, the Tribunal includes the facts leading to the application, as they may assist the reader to understand what appears to be a need for legislative clarification of the registration of so-called biological medications. The 2014 amendments to the Act provided that biological medications may be assessed and registered on the basis of their biosimilarity to medications approved in accordance with the Mutual Recognition Convention of Geneva, edicts of national regulatory authorities and the European Medicines Agency (EMA and formerly EMEA, European Medicines Evaluation Agency). These amendments to the Act are reflected in the substance of the PI attached to the application.

  9. In Australia, the medical profession is informed of the availability of new medications and the PI is reproduced in the publication known as MIMS (the Monthly Index of Medical Specialties, edited in the United Kingdom and provided to several jurisdictions throughout the world). The PI is both instructive and educational.  The Tribunal is aware that in the past 10 to 20 years there has been a major acceleration in the development of monoclonal antibody agents for use in the treatment of both inflammatory disorders and malignancy. These medications have attracted a vast coverage in the daily press.

  10. The Applicant, Hospira, became a fully owned subsidiary of Pfizer in August 2015. Janssen is the pharmaceutical company providing research functions for Johnson & Johnson, with whom it merged in 1961. Janssen developed the monoclonal antibody known as Remicade® the active component of which is Infliximab. Hospira’s monoclonal antibody, marketed as INFLECTRATM (Inflectra), has the same active component Infliximab. Remicade® received approval in multiple jurisdictions in August 2000. Infliximab binds to and blocks the activity of Human Tumour Necrosis Factor alpha (TNFα). TNFα activates pro-inflammatory enzyme cytokines said to mediate (i.e. play a role in) certain disease processes. These include rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease and ulcerative colitis. By blocking the effect of increased amounts of TNFα, Infliximab positively improves the performance of certain other cytokines, activates neutrophils, alters the status of endothelial cells and induces proliferation of cells such as fibroblasts.

  11. Infliximab is an antibody and a gamma globulin. It is produced by harvesting human cells of various types, injecting them into genetically modified mice which produce the monoclonal antibody. This is harvested and tissue cultured to produce a monoclonal antibody targeted at a specific receptor site on the host cell membrane. Using recombinant DNA techniques this can be altered to target two receptor sites. The immunoglobulin is converted to a powder mixed with a variety of excipients. Given the number of variables present including the human source, the mouse/murine host, the harvesting and tissue culture procedures and then the actual presentation in a powdered form reconstituted with various diluents and pH correcting chemicals, no two batches of Infliximab are the same, let alone those produced by different pharmaceutical companies. They may be biosimilar but they are not bio-identical. 

  12. The first of the three amendments to Hospira’s PI under challenge relates to the extrapolation of data from Remicade® trials to Hospira’s Inflectra and in particular to the indications for its use in gastro-intestinal disease. The second amendment in contention, based on the lack of clinical trial data, relates to the switching provisions, that is, the switching from one Infliximab product to another. The third and final amendment in dispute concerns traceability, which is measured in terms of the availability of dispensing records, entries in the patient’s medical file and the like. This is to ensure that the Infliximab product dispensed can be identified unequivocally.

    RELEVANT LEGISLATION

  13. The parts of the Act relevant to the primary legal construction question are as follows:

    4Objects of Act

    (1)The objects of this Act are to do the following, so far as the Constitution permits:

    (a)provide for the establishment and maintenance of a national system of controls relating to the quality, safety, efficacy and timely availability of therapeutic goods that are:

    (i)used in Australia, whether produced in Australia or elsewhere; or

    (ii)exported from Australia;

    …

    9DVariation of entries in Register

    (1)The Secretary may:

    (a)following a request by a person in relation to whom therapeutic goods are entered on the Register; or

    (b)on the Secretary’s own initiative;

    vary the entry in the Register in relation to the goods if the entry contains information that is incomplete or incorrect.

    ...

    (3)If:

    (a)the person in relation to whom therapeutic goods are registered or listed has requested the Secretary to vary information included in the entry in the Register that relates to the goods; and

    (b)subsection (2) does not apply to the request; and

    (ba)subsection (2C) does not apply to the request; and

    (c)the Secretary is satisfied that the variation requested does not indicate any reduction in the quality, safety or efficacy of the goods for the purposes for which they are to be used;

    the Secretary may vary the entry in accordance with the request.

    (3AA)If:

    (a)the person in relation to whom a biological is included in the Register has requested the Secretary to vary information included in the entry in the Register that relates to the biological; and

    (b)the only effect of the variation would be:

    (i)to reduce the class of persons for whom the biological is suitable; or

    (ii)to add a warning, or precaution, that does not include any comparison of the biological with any other therapeutic goods by reference to quality, safety or efficacy;

    the Secretary must vary the entry in accordance with the request.

    (3A)If:

    (a)the person in relation to whom a biological is included in the Register has requested the Secretary to vary information included in the entry in the Register that relates to the biological; and

    (aa)subsection (3AA) does not apply to the request; and

    (ab)subsection (3AC) does not apply to the request; and

    (b)the Secretary is satisfied that the variation requested does not indicate any reduction in the quality, safety or efficacy of the biological for the purposes for which it is to be used;

    the Secretary may vary the entry in accordance with the request. ...

    23Applications generally

    (1)An application for registration or listing of therapeutic goods must:

    (a)be made in accordance with a form approved, in writing, by the Secretary or in such other manner as is approved, in writing, by the Secretary; and

    (b)be delivered to an office of the Department specified by the Secretary.

    (2)An application is not effective unless:

    (a)the prescribed application fee has been paid; and

    (b)the applicant has delivered to the office to which the application was made such information, in a form approved, in writing, by the Secretary, as will allow the determination of the application; and

    (ba)if the application is for the registration of restricted medicine—the application is accompanied by product information, in relation to the medicine, that is in the form approved under section 7D in relation to the medicine; and

    (c)if the Secretary so requires—the applicant has delivered to the office to which the application was made a reasonable number of samples of the goods.

    25Evaluation of therapeutic goods

    (1)If an application is made for the registration of therapeutic goods in relation to a person in accordance with section 23, the Secretary must evaluate the goods for registration having regard to:

    (d)whether the quality, safety and efficacy of the goods for the purposes for which they are to be used have been satisfactorily established; and

    (da)if:

    (i)the applicant is applying for the registration of restricted medicine; or

    (ii)the applicant is applying for the registration of medicine (other than restricted medicine) and the applicant has been given a notice in writing by the Secretary requiring the applicant to give to the Secretary product information, in relation to the medicine, that is in the form approved under section 7D in relation to the medicine;

    the product information given by the applicant in relation to the medicine; and

    …

    (3)After an evaluation under this section of goods has been completed, the Secretary must decide:

    (a)to register the goods; or

    (b)not to register the goods.

    Note:See also sections 25AA (approved product information for medicine), 25AB (registration of therapeutic goods) and 25AC (notice of decision not to register therapeutic goods)..

    25AAApproved product information for medicine

    (1)The Secretary must approve product information in relation to therapeutic goods if:

    (a)the Secretary decides, under subsection 25(3), to register the goods; and

    (b)the goods are:

    (i)restricted medicine; or

    (ii)medicine in respect of which the applicant has been given a notice of the kind referred to in subparagraph 25(1)(da)(ii).

    Note:Subsection (4) deals with variation of the product information.

    (1A)However, the Secretary must not approve product information in relation to therapeutic goods under subsection (1) unless the Secretary is satisfied that the product information reflects the basis on which the Secretary decided under subsection 25(3) to register the goods.

    …

    Variations

    (4)If:

    (a)there is medicine included in the Register in relation to a person and there is product information approved under this section in relation to the medicine; and

    (b)either:

    (i)under section 9D, the Secretary varies the entry in the Register in relation to the medicine; or

    (ii)there is a change in the conditions to which the inclusion of the medicine is subject; and

    (c)as a result of that variation or change, the Secretary is satisfied that  variation to that product information is required;

    the Secretary may, by notice in writing given to the person, make any variations that the Secretary considers appropriate to the product information that is approved in relation to the medicine.

    (4A)Without limiting subsection (4), a variation to the product information is not appropriate unless:

    (a)if subparagraph (4)(b)(i) applies—the product information, as varied, reflects the basis on which the Secretary decided under section 9D to vary the entry in the Register in relation to the medicine; or ...

    …

    25ABRegistration of therapeutic goods etc.

    …

    (2)If:

    (a)an application is made in accordance with section 23 for the registration of therapeutic goods in relation to a person; and

    (b)the Secretary decides under subsection 25(3) to register the goods; and

    (c)the goods are not therapeutic devices;

    the Secretary must, in accordance with subsection (3), notify the applicant in writing of the decision within 28 days of making the decision.

    (3)The notice must:

    (a)set out the decision under subsection 25(3) to register the goods; and

    (b)if the goods are restricted medicine or medicine in respect of which the applicant has been given a notice of the kind referred to in subparagraph 25(1)(da)(ii)—set out the product information approved under subsection 25AA(1) for the medicine; and

    (c)inform the applicant that the goods will not be included in the Register unless and until the applicant gives the Secretary:

    (i)the certificate required under subsection 26B(1); or

    (ii)a notice (in accordance with a form approved, in writing, by the Secretary) that a certificate under that subsection is not required in relation to the application.

    …

  14. In addition the TGA publishes information on its website regarding PI. This advises that a PI should contain the following information:

    ·name of the medicine

    ·description

    ·pharmacology

    ·clinical trials

    ·indications

    ·contraindications

    ·precautions

    ·adverse effects

    ·dosage in administration

    ·over dosage

    ·presentation and storage conditions

    ·name and address of the sponsor

    ·poison schedule of the medicine

    ·date of approval

  15. With respect to the question of statutory interpretation, ss 4 and 25AA are the most relevant sections of the Act.

  16. The Act has been subject to several attempted amendments. That of 2013 lapsed, apparently for lack of support in the Upper House of Parliament. As Hospira applied for registration of its biological medicine on 2 September 2013 the consideration/evaluation process has traversed a period wherein there were two proposed amendments to the Act. The Tribunal has been informed that this particular application was the first to be assessed by the TGA under the biosimilar provisions.

    THE PARTIES SUBMISSIONS

  17. Written submissions were provided by all parties to these proceedings and the legal representatives spoke to these submissions. Hospira and Pfizer accepted and agreed with the submissions made by the Minister. Mr Kirk SC for Hospira and Pfizer provided some additional submissions and made reference to authorities which will be addressed.

    Submissions for the Minister

  18. In both his written and oral submissions, Mr Pizer addressed the steps required in the application for registration of a therapeutic good and in particular Inflectra. He contended that Hospira had satisfied all of these requirements for Inflectra (while reference was made to the four alternative trade names to be attracted by Hospira’s monoclonal antibody, the active component of which is Infliximab, the trade name Inflectra is used throughout this decision).

  1. The major contention of the Minister’s arguments relate to s 25AA of the Act. Should the Tribunal accept the legal construction advanced by Mr Pizer, this would result in the Minister’s delegate’s reviewable decision being ultra vires as he did not have the power to make the variations that are the subject of the substantive application. Three matters were identified for consideration:

    (a)The proper construction of and characterisation of the task to be performed under s 25AA;

    (b)In relation to the product information provided by the applicant, whether the Secretary’s delegate can refuse to approve the version provided by the Applicant and then proceed to approve a modified version of that document; and

    (c)The meaning of the words reflects the basis on which the Secretary decided to register… the goods as they are found in s 25AA(1A) of the Act.

  2. Mr Pizer addressed each of these in turn. In relation to s 25AA(1) it was contended that the Act imposed a duty on the Secretary to approve the PI in relation to the goods that are a restricted medicine and the Secretary has decided to register those goods. It was argued that this duty carried with it an implied power to approve the Product Information.

  3. Mr Pizer rejected Janssen’s submission that the power was a broad discretionary one submitting that it was a confined power that must be exercised to give effect to the performance of the statutory duty. The only restrictive provision was that contained in s 25AA(1A) which prohibited the Secretary from approving the PI unless the Secretary is satisfied that the product information reflects the basis on which the Secretary decided ... to register the goods. Mr Pizer classified this as a constraint on the performance of the statutory duty, as opposed to Janssen’s contention that it was a free standing condition.

  4. With regard to the PI, Mr Pizer noted the requirement that it must follow the form dictated by s 7D. It was contended this requirement did not require the applicant to draft the PI in one way and one way only as it was not the Secretary’s role to decide whether the PI is drafted in the best possible way, nor is it the Secretary’s role to settle the PI provided by the applicant.

  5. The Secretary’s task was identified as being to determine whether the final version of the PI given to them reflected the basis upon which the decision to register the goods was made. If it did reflect the basis of the decision, the Secretary then had a statutory duty to approve the PI. The Act was silent as to amendment, variation or rewrite where, in the Secretary’s view, the information did reflect the basis upon which they determined to register the goods. 

  6. Where the Secretary determined that the PI did not reflect the basis on which they had decided to register goods, the Secretary must not approve that PI. Section 25AA(4) of the Act addresses variations to the PI. Sections 25AA(4) and 25AA(4A) frame the Secretary’s power to vary PI and this differs strikingly from s 25AA(1A) in that the former provide the Secretary with a broad power to make variations he or she considers appropriate but only if certain preconditions are met. No such preconditions apply to s 25AA(1).

  7. Mr Pizer addressed the question of what the Secretary can do if, having assessed the final version of the PI in accordance with the requirements of s 25(1)(da), the Secretary determines that the PI does not reflect the basis of the registration decision. It was contended that the options available to the Secretary in these circumstances were to:

    (a)modify the PI document so that it reflects the basis of the decision to register the goods; or

    (b)to discuss the matter with the applicant and to ask the applicant to provide a revised version of the PI.

  8. Mr Pizer drew attention to Janssen’s Statement of Facts and Contentions and submitted that they had misunderstood the Minister’s Statement of Facts and Contentions in relation to s 25AA(1) of the Act, Janssen having interpreted the submission by the Minister as being that the Act does not allow the Secretary to approve product information ... in anything other the form proposed by the applicant. Mr Pizer stated the Minister did not make that submission and does not do so now.

  9. Mr Pizer next addressed the meaning of the words reflect the basis as applicable to the approval of PI and the Secretary’s earlier decision to register the therapeutic goods in question. In doing so he referred to the Oxford Encyclopaedic English Dictionary (1991) and the Macquarie Concise Dictionary (5th Ed, 2009). It was contended that the basis on which the Secretary made the decision was not synonymous with the reasons for that decision but that the basis for the decision should be synonymous with the reasons underlying the decision. This was consistent with Hospira and Pfizer’s contention that it was the understanding and reasoning which founded the decision. Mr Pizer also submitted this was consistent with Janssen’s contention that the basis on which the Secretary made the decision was the underlying support or foundation for that decision. Mr Pizer did not rely strongly on the wording of this argument as, in his opinion, there were no significant differences between the formulations put forward by the parties.

  10. Mr Pizer concluded with the submission that the Tribunal should determine that the Secretary’s statutory task was to decide whether the final version of the PI given to him or her reflected the basis upon which he or she decided to register the goods. If it did, the Secretary must approve the PI. If it did not, the Secretary must take steps to ensure that his or her statutory duty to approve the PI was performed. It was further submitted that, as a result of such a conclusion, the Tribunal should find;

    ... [I]t was not open to the Minister’s delegate to undertake the review of Dr Mackay’s decision to approve the PI for INFLECTRA on the basis that s 25AA of the Act confers a wide discretionary power to vary, amend or rewrite the product information provided by the applicant.

    … [I]t was not open to the Minister’s delegate to revoke Dr Mackay’s decision to approve the product information for INFLECTRA unless he was satisfied that the product information did not reflect the basis of Dr Mackay’s decision to register that medicine.

  11. It was contended that, as the decision of the Minister’s delegate was ultra vires, the appropriate decision for the Tribunal to make would be to set aside and remit the decision under review to the Minister for reconsideration.

    Submissions for Hospira and Pfizer

  12. Mr Kirk on behalf of Hospira and Pfizer essentially agreed with the submissions of the Minister and summarised this as being three major contentions that:

    (a)nothing in s 25AA granted a broad discretion of the kind assumed by the delegate, rather the power was closely defined;

    (b)in practice the approved PI is most probably the version of the PI the Secretary agreed to at the time he or she decided to register the therapeutic goods; and

    (c)that there is no power under s 25AA and the review power of s 60 to make the three amendments to the PI that formed the substantive issue before the Tribunal.

  13. Mr Kirk spoke to his written submissions but first acknowledged that submissions made on behalf of Hospira and Pfizer as to the statutory construction question were substantially in agreement with those put by the Minister, with a slightly different emphasis placed on certain points. While agreeing with Mr Pizer that s 25AA imposed a duty on the Secretary and any power was an implied power, Mr Kirk stressed that the Secretary could only fulfil the duty if he or she had the power to do so. The Secretary must approve the PI if the criteria are met. It was contended that there was a complete absence in ss 25AA(1) and 25AA(1A) referencing any existence of a broad discretion to be exercised.

  14. With respect to the PI, Mr Kirk first addressed the requirements provided by s 23(2)(ba) as further refined by ss 25(1)(da)(i) and 25(1)(da)(ii). He concurred with the Minister’s contentions that the Secretary does not prepare the PI or make changes to ensure it is drafted in the best possible way. Section 25(1)(da) states that the PI is given to the Secretary by the applicant. In making this contention Mr Kirk relied on the decision of Jagot J in Sanofi-Aventis Australia Pty Ltd v Apotex Pty Ltd (No 4) (2011) 202 FCR 56 at 66-67, wherein the Court’s reasoning supported the proposition that the Secretary’s role is to approve information, not a particular form of expression of information. Reliance was also placed on the decision of the Administrative Appeals Tribunal in Re Pfizer Pty Ltd and Department of Health, Housing and Community Services (1993) 30 ALD 647 at 654 where the Tribunal noted that:

    ... The approved product information is intended to present a concise and objective account of the characteristics of the drug, the indications for which it has been found effective, any contra-indications and warnings that apply, any precautions that have to be observed, the adverse effects that have been noted, along with the order of their frequency, the recommended dose and the method of dosing.

  15. Mr Kirk contended that the content of the PI is intimately linked with the approval of the therapeutic good itself, this being implicit in the statutory definition and description. The PI provided by the applicant is the subject of discussion and negotiation during the course of the consideration by the TGA for the purpose of registration. It was argued that the two processes cannot be meaningfully divorced as they are intertwined, although subject to minor corrections over the two and a half years taken to assess Hospira’s application for registration of Inflectra by the TGA. It was submitted that the final version of any PI, would have been completed, subject to minor corrections, at the time of the s 25(3) registration decision and the two are issued simultaneously.

  16. Mr Kirk conceded that having had the benefit of reading the Minister’s submissions, much of Hospira’s stated facts and contentions and some of their submissions on the statutory construction issue were now abandoned.

  17. Mr Kirk did address some aspects of Janssen’s submissions. He contended that s 25AA(4), in relation to variations, was very confined in its application and this also extended to s 9D(3AA) in relation to biologicals. The latter provides that variation is only permitted if it is to reduce the class of persons for whom the biological is suitable or to add a warning or precaution that does not include any comparison with any other therapeutic goods by reference to quality, safety or efficacy.

  18. Mr Kirk addressed Janssen’s submissions in some detail and again submitted that the PI and the registration of the therapeutic good, in this case Inflectra, were so intertwined that they cannot be divorced, quoting the Explanatory Memorandum (EM) to support this submission. The EM relating to the Therapeutic Goods Amendment (2013 Measures No.1) Bill presented to the Parliament by the then Minister for Health, the Honourable Peter Dutton, stated at page 29:

    In summary, both proposed subsection 25AA(1A) and 25AA(4A) are intended to capture current practice in the approval of product information by the Secretary under the Act.

    This was said to be exemplified by Dr Mackay’s carriage of the matter, where the accepted PI version was approximately the eighth agreed upon after enquiry and consultation over a lengthy period of time.

  19. Janssen’s construction of the statute, in particular that ss 25AA(1) and 25AA(4) were in harmony and empowered the Secretary with the responsibility to approve PI in an appropriate form, which may or may not be the same as that submitted by the applicant, was rejected on the basis that Parliament had carefully distinguished between these two sections. Mr Kirk relied on the High Court of Australia’s decision in Project Blue Sky Inc and Others v Australian Broadcasting Authority (1998) 194 CLR 355, where the majority (McHugh, Gummow, Kirby and Hayne JJ) said at 381-382:

    The primary object of statutory construction is to construe the relevant provision so that it is consistent with the language and purpose of all the provisions of the statute. The meaning of the provision must be determined "by reference to the language of the instrument viewed as a whole". ... Thus, the process of construction must always begin by examining the context of the provision that is being construed.

    A legislative instrument must be construed on the prima facie basis that its provisions are intended to give effect to harmonious goals…

    Furthermore, a court construing a statutory provision must strive to give meaning to every word of the provision…

  20. It was submitted that the effect of Janssen’s construction of the sections would be that the words considers appropriate within s 25AA(4) would be rendered superfluous as they were not needed for the ss 25AA(1) and 25AA(1A) power.

  21. Mr Kirk made further submissions regarding the Minister’s delegate’s view that he could vary, amend or re-write the PI. This contention was illustrated by the use of phrases and words in the delegate’s decision such as Result of my reconsideration and Decision to approve an amended version, suggested that the Secretary’s delegate’s mindset was what he thought was appropriate. This was evidence of the delegate’s assumption that he had a broad discretion as to how he approached his task. In a similar vein, the delegate had expressed his opinion as to what he considered was unreasonable and reasonable, without reference to the Act.

  22. Mr Kirk accepted that he, on behalf of Hospira, had shifted position having conceded that the Minister’s interpretation of the Act was correct.

    Submissions for Janssen-Cilag

  23. Mr Free had provided the Tribunal with written submissions but, like Hospira, he digressed from these as the contentions of both Hospira and the Minister had led him to conclude that neither of them suggested a hard line division between the functions of the drafter of the PI (Hospira) and the decision-maker. He submitted it was open for the Secretary to approve the PI under s 25AA(1) in a form that differed from that proposed by the applicant, although he acknowledged that the Minister had used the term modified as opposed to differed. While it was further acknowledged that the Minister did not say it was the role of the Secretary to settle the words of the product information, it was accepted that in some circumstances it could be that role.

  24. In the event that it was common ground regarding the existence of the power to approve product information Mr Free submitted it was open to the delegate to do what they did in adopting the changes to the PI.

  25. Mr Free contended that there was no presumption to favour what the applicant, Hospira, wanted in terms of the PI content or formulation. The Secretary’s task was identified as asking himself or herself what was the appropriate form of the PI to be approved and basing the decision on the requirement that they must ensure that whatever is approved reflects the basis on which the decision to register was made. In other words, the question raised for the Secretary to determine was; what is the PI that I should approve that reflects the basis of the decision to register the goods? 

  26. Mr Free submitted that the Minister and Hospira erred in assuming that a choice in regard to the PI to be accepted was constrained by what the applicant chose to put in the PI whether by negotiation with the TGA or otherwise.

  27. Mr Free identified s 23 and its requirements as the trigger for the process of evaluation and registration of a therapeutic good. He contended that the original PI submitted at the time of the application would rarely be suitable for approval as it was only at the end of the assessment process that the correct, or what he called, appropriate PI could be determined. Clearly, the power to determine an application for registration related to the Secretary’s obligation to evaluate the goods for registration. Section 25(1)(da) requires the Secretary, in evaluating the goods for registration, to have regard to the PI.

  28. Mr Free submitted that the power of s 25AA(1), while expressed in terms of a duty, was in fact a conferral of implied power to approve. That power was to approve the product information and would miscarry if the information approved did not relate to the safe and effective use of the goods. Given the wording of s 25AA(1), Mr Free contended that the approval was not of a document but of the information therein and as such, did not support the Minister’s argument that the PI submitted by the applicant is the starting point for the Secretary’s approval.

  29. Turning to s 25AA(1A) Mr Free submitted that (1A) was a constraint on the exercise of the power given the wording of the subsection provides:

    However, the Secretary must not approve product information unless: …

    Citing the EM to the Therapeutic Goods Amendment (2013 Measures No. 1) Bill 2013, he also argued that Item 4 of Schedule 5 of the Therapeutic Goods Amendment (2013 Measures No. 1) Act 2014 was intended to amend s 25 in order to provide greater clarity and purpose to s 25AA(1) but there was no indication that this was the end-all or be-all in considering approval of the PI.

  30. Mr Free further contended that the Minister and Hospira were endeavouring to compress ss 25AA(1) and 25AA(1A) into one entity and that further consideration of the old version of the Act and the new subsection s 25AA(1A) left open the power to further change the product information.

  31. Mr Free quoted the EM where it was stated that:

    In summary, both proposed subsection 25AA(1A) and 25AA(4A) are intended to capture current practice in the approval of product information by the Secretary under the Act

    While there was a prohibition against inconsistency, there was no guidance provided as to what should be approved. The same applied to the old Act and as a result the power to approve PI was implied through the Secretary’s obligation to notify an applicant of the approval of PI. It was submitted that the amendments contained within the Therapeutic Goods Amendment (2013 Measures No. 1) Act 2014 were an attempt to clarify that power’s existence, maintain the continuity of its scope and introduce a requirement of consistency.

  32. Mr Free submitted that Hospira and the Minister’s construction, broadened the concept of consistency to something which shifted the outer limits of consistency to the extent that:

    ... if the applicant puts up something which isn’t inconsistent with the registration decision then the Secretary is bound to approve it.

  33. Mr Free contended that while the Minister had argued that there was ongoing consultation between the sponsor and the Secretary’s delegate in regard to the PI and while he agreed that this was a sensible practice, it was not reflected in the statute. He further argued that it will be a very odd scheme if the discretion to vary contained in s 25AA(4) did not extend to the initial PI.

  34. In summary, Mr Free submitted that the two sections could not be compressed into one as s 25AA(1) was to be understood as implicitly empowering the Secretary to approve the PI in appropriate form and the exercise of that power was subject to the separate condition in s 25AA(1A).

  35. In closing, Mr Free contended that acceptance of the Minister and Hospira’s interpretation would prevent the Secretary or their delegate from further internal review of a PI and such a preclusion would extend the Administrative Appeals Tribunal.

    Further Submissions for the Minister

  36. Ms Foley responded on behalf of the Minister and directed the Tribunal’s attention to several points. These were:

    (a)That, in relation to Item 5 of Schedule 5 to the Therapeutic Goods Amendment (2013 Measures No. 1) Act 2014, the EM addressed the Secretary’s powers and the requirement that the Secretary approve PI if they had decided under s 25(3) to register the goods for which PI was required to accompany the application. The criteria for not approving the product information were delineated and it was stated that this measure was intended to refer to the importance of the product information not being inconsistent or out of step with the basis on which the Secretary had decided that the medicine was suitable for registration. Further, and in particular, the EM stated that this measure was not intended to change the nature or extent of information currently included in the product information approved by the Secretary. Nor was there an intention to imply that the product information was intended to be a comprehensive record of all the information that was before the Secretary.

    (b)Section 23(2)(ba) required the application for registration to be accompanied by a PI. Ms Foley contended that if the Secretary could redraft the PI from a clean slate, there would be no purpose to s 23(2)(ba).

    (c)Section 25(1)(da) of the Act stated that the PI was to be considered in the evaluation.

    (d)The terminology must approve formed a requirement of s 25AA(1).

    (e)Mr Free’s argument relating to the statutory scheme only contemplated one PI and that it could not be amended by the applicant during the process of evaluation. It was in fact TGA practice to amend the PI where necessary and to do so in consultation with the sponsor.

    (f)It was submitted that the merits review process was not excluded by the respondent’s interpretation of the statute. It was open for merits review where the PI did not reflect the basis of the registration, where the PI was said not to reflect the basis of the registration but in fact did so and should have been approved and thirdly, where the challenge was to both the registration and the PI.

  1. Ms Foley submitted that if the Secretary decided to register goods falling within s 25AA(1)(b), taking into account the safety and efficacy as required by the Act, then the Secretary must approve the PI as that is where the statutory duty to perform arises.

  2. Ms Foley reiterated the Minister’s earlier construction that s 25AA(1) relates to the statutory duty which carries with it an implied power and s 25AA(1A) is a constraint on the performance of that duty. It was open to the Secretary to go back to the applicant when they were not satisfied that the product information reflected the basis of the decision to register and request that the applicant readdress or alter the product information to do so. If this occurred, the Secretary would be expected to approve the PI. However, the Secretary retains the power to approve a PI that is not identical to that originally provided if it reflects the basis of the decision to register. As a corollary to this argument, the Secretary cannot go further and settle the product information simply because the Secretary thought it could be drafted in a better or different way. Where there was poor or inadequate product information a decision to register should not be made.

  3. Ms Foley contended that if Janssen had concerns regarding the safety of the product they should challenge the registration decision rather than endeavour to alter the product information. It was concluded that the entire process of registration and approval of the PI had miscarried. Further submissions were made as to Dr McEwen’s stated views (e.g. that the biosimilar data was not sufficiently informative) that other words were to be preferred than those in the final PI and in particular Dr McEwen’s reference to a scientific publication which he took into consideration but had not been before Dr Mackay when she made the initial determination.

    Further Submissions for Hospira and Pfizer

  4. Mr Kirk, in response to Mr Free’s submissions, made six points:

    (a)Janssen’s submission that both the Minister and Hospira sought to run ss 25AA(1) and 25AA(1A) together was totally rejected.

    (b)It was submitted that, as the appropriateness criterion was explicitly mentioned in s 25AA(4), that subsection constituted a different power with different content in comparison to s 25AA(1).

    (c)The EM made it clear that the decision to approve the PI had to reflect the basis for the decision to register.

    (d)Submissions made by Hospira and the Minister were based on current TGA practice. The PI was intertwined and undivorceable from the actual consideration of registration, at least in practical terms.

    (e)All parties were in agreement as to the meaning of the phrase reflect a basis and the only challenge made by Janssen was to the PI. As no reasons were required to be given by either Dr McEwen or Dr Mackay, no conclusions could be drawn by the Tribunal.

    (f)The argument raised by Mr Free in relation to ‘A flagging’ was rejected as it was not part of the decision and had not been challenged by any party prior to the decision.

    Dr Kerri Mackay

  5. The Tribunal elected to hear from Dr Mackay and did so in order to ascertain the details of the evaluation, assessment and decision making processes leading to registration and PI approval. The Tribunal deemed this information to be vital in view of the statements made in the EM (pages 28 and 29).

  6. Under the heading Items 5 and 8 (of Schedule 5 of the Therapeutic Goods Amendment (2013 Measures No. 1) Bill 2013) in the EM, the then Minister for Health, The Honourable Peter Dutton MP, stated (emphasis added):

    The intention is to require that those key pieces of information about a medicine that make up the product information align with, and do not contradict, the registration decision or the considerations that led to the Secretary to approve the medicine for registration.

    This measure principally reflects that the product information is an integral component of the decision to register the medicine, and the fact that the content of the product information essentially underpins that registration decision including in relation to the quality, safety and efficacy of the medicine.

    ... A decision to register a medicine would not be made unless the Secretary was satisfied that the content of the product information to be approved was accurate in properly reflecting the circumstances in which the medicine was considered suitable for registration. (Emphasis added)

  7. Having addressed the amended s 25AA(4) the Minister concluded:

    In summary, both proposed subsection 25AA(1A) and 25AA(4A) are intended to capture current practice in the approval of product information by the Secretary under the Act.

  8. Hence, the Tribunal determined that in order to address the preliminary statutory interpretation issue, the practice and procedure of the TGA in relation to biosimilar medicines required detailing.

  9. Much of Dr Mackay’s evidence has been redacted on the basis that it involves commercially sensitive information. However it was never the Tribunal’s intention to ascertain such information, merely the details of the practice and procedure of the TGA.

  10. Dr Mackay has been employed as a registered medical practitioner by the TGA since 2008. She is the Director of Clinical Evaluation Unit 1 (Unit 1). There are five clinical evaluation units in the TGA. Unit 1 is responsible primarily for neurological and psychiatric medications, anaesthetic medications and those prescribed for skin disorders, nutrition and gastrointestinal disorders. The Inflectra evaluation and assessment was assigned to Unit 1, as they had a relatively light workload and also because the most contentious indications for the use of Inflectra and Remicade® relate to its use in Crohn’s disease, ulcerative colitis and potentially other bowel disorders.

  11. Dr Mackay provided two affidavits, that of 4 November 2016 (Exhibit R2) and the second of 6 June 2017 (Exhibit R3). The latter was in response to Janssen’s Statement of Facts and Contentions filed with the Tribunal on 1 November 2016.

  12. As Dr Mackay was the respondent’s witness, Mr Pizer commenced examination-in-chief. Mr Free objected to this procedure as he contended that the Tribunal should rely on the content of the affidavits. It was determined that the examination-in-chief would be limited to the process and procedures about which the Tribunal wished to be informed.

  13. Dr Mackay gave evidence that the process normally started with the sponsor requesting a pre-submission meeting with the TGA. This was a general discussion regarding what was proposed to be submitted and what information was required by the TGA. Once enough information was provided to identify the areas that may be of concern, various groups or individuals within the TGA were contacted. In this case the biochemical and biological aspects were referred to the biochemistry division and toxicology aspects to the toxicology division of the TGA. Biological medicines were at that time assessed by a biochemist. A clinician employed full time by the TGA evaluated the clinical trial data. In response to the Tribunal’s questions as to why an external expert in the area was not involved, Dr Mackay informed the Tribunal that in the case of Inflectra, an external expert opinion was obtained. Such services were available in all cases but generally internal evaluators were used for shorter submissions. The more complex or lengthy submissions did attract external expert opinion. The Tribunal’s suggestion that the length of the submission would reflect the complexity of the matter was accepted by Dr Mackay.

  14. The Tribunal also questioned whether it might have been more appropriate for the Inflectra assessment to be referred to the infection and inflammation unit, identified as Unit 2. Dr Mackay explained that while infections of the gastrointestinal tract were dealt with by Unit 2, other aspects of gastrointestinal pathology came to Unit 1 through a workload-sharing arrangement.

  15. Dr Mackay gave evidence in relation to the external expert opinion that was obtained. As this is subject to a Confidentiality Order it is not addressed further.

  16. Dr Mackay outlined the various steps and stages in the process of evaluation, the mode of action of Inflectra and Remicade® in relation to the inflammatory disorders of joints, skin and bowel and the intra-agency discussions between the various units and the sponsor. She also addressed the results of the clinical trials. These are subject to the Confidentiality Order.

  17. The concerns that the Tribunal had in relation to the clinical trials were addressed and resolved to the Tribunal’s satisfaction. It was clear that the clinical trials were assessed and interpreted depending on the country where they were performed and note was taken of the local incidence of various infective medical conditions. In the area of biosimilar medicines or as the medical profession terms them, immuno-modifiers, Dr Mackay said it was common to transfer the pharmacokinetics of a particular reference agent to those under consideration.

  18. Dr Mackay described her responsibilities as ensuring the quality, safety and efficacy of the intended uses. She had been intimately involved in the assessment of the PI data and where she had any concerns she consulted with the sponsor.

  19. On 5 August 2015 Dr Mackay decided to register the biosimilar medicine Inflectra and to approve the PI finalised during the consultation processes conducted over nearly two years. She had had carriage of the final decision-making process for approximately five months.

  20. In cross-examination by Mr Free (for Janssen), Dr Mackay confirmed the contents of her first affidavit and that there were eight stages in the process of evaluation, assessment and approval. She had taken into account any issues raised by the TGA evaluators and external experts and how the sponsor had responded to these issues. She agreed with Mr Free that the degree of assistance required by the medical profession and other health professionals required from the PI would vary depending on their individual level of expertise and experience in their specialty.

  21. Dr Mackay said that most physicians using Inflectra were experts in their area of specialisation and as this monoclonal antibody had to be given by intravenous infusion it necessitated a stay in a day procedure unit or hospital. She said that, generally speaking, these experts had experience with similar monoclonal antibody products and were well acquainted with the characteristics of the medicine, its adverse side effects and the precautions to be taken. She agreed that other health professionals, such as nurses and pharmacists, would access the PI when they were involved in providing treatment but also in order to acquire information for general knowledge purposes. The Tribunal asked if the use of Inflectra or Remicade® would be confined to a very small expert medical population. Dr Mackay said that this was very much the case.

  22. Dr Mackay agreed with Mr Free that in that case of Inflectra there would be less familiarity amongst experienced specialists as Inflectra was a new biosimilar and the first to be submitted to accreditation by the TGA.

  23. Mr Free posed several questions in relation to the procedure of assessment and evaluation and in relation to the PI content. Dr Mackay stated that where she considered that information provided by the sponsor did not impact on the objects of the Act, namely, the quality, safety and efficacy of the therapeutic medicine, she would not refer to it in her decision. This absence of reference did not mean she had not considered it. She regarded speculative data and statements as being so speculative and theoretical that they should not be considered. There were, however, exceptions to her adopted procedure. She gave an example relating to the duration of follow-up periods. Where there was a short follow‑up period of the experience and use of a biological, e.g. to only six months, she would refer to this in her decision. Additionally, if the follow-up period was greater than two years she would be satisfied that any concern regarding efficacy and safety had been resolved and she would therefore also mention it.

  24. Dr Mackay was familiar with the changes proposed by Dr McEwen in his review decision. She advised that this version had not yet been accepted by the Minister. With respect to the document published by the TGA and known as AusPAR (Australian Public Assessment Report) which provides more information about the process leading to registration and more extensive data relating to the PI, this had been prepared for Inflectra but had not yet been published.

  25. Mr Free took Dr Mackay to all of the so-called precautions which, as far as the Tribunal was concerned, were the norm in all PI’s and relate to the risk of malignancy and those relating to pregnancy, fertility and lactation. She explained to the Tribunal’s satisfaction that the timeframe was insufficient with respect to the development of neoplasia. The general advice that was given with respect to fertility and advice in relation to pregnancy and lactation was based on the fact that Infliximab is known to cross the placenta and to be present in breast milk. While no absolute data was available with respect to these possible risks, Dr Mackay had adopted the same theoretical risks in relation to Inflectra as had Janssen in its PI in relation to Remicade®.

  26. The TGA has adopted the European Medicines Agency (EMA) Guidelines with respect to biosimilars but, according to Dr Mackay, also has its own guidance document. In accordance with the EMA, the TGA accepts the extrapolation of clinical data, one to the other, if it is scientifically justified. Further discussion of this subject was subject to a Confidentiality Order.

  27. The clinical trial data relied on by Hospira had been, in the main, conducted by Janssen and Dr Mackay agreed that the PI should acknowledge that the data referred to the reference medicine, not Inflectra. She would not have identified the reference medicine by its trade name Remicade®.

  28. Dr Mackay was confident that people reading the PI would understand that the clinical trial data included in the PI had been extrapolated to the biosimilar from the reference medicine and those prescribing the biosimilar would fully understand the source of the data.

  29. Dr Mackay’s evidence on switching between biosimilar medicines in the course of an individual’s treatment, a common occurrence, was subject to the Confidentiality Order. However, the comparability of Inflectra and Remicade® with respect to the development of antibodies to Infliximab following a single switch was similar. Antibodies were detected but the antibody titre (level) has not been disclosed. Should further evidence come to light, the TGA would consider it. In the interim, given the differences between Infliximab batches due to numerous variable factors, the TGA has declined to make positive statements regarding immunogenicity based on theoretical risk.

  30. Dr Mackay agreed with Mr Free that, in her final version of the PI, she had requested that the following sentence be removed from the proposed PI:

    Replacement of Remicade® with Inflectra should take place only under the supervision of the prescribing medical practitioner.

    The inclusion of this particular requirement or suggestion had been made by the Advisory Council on Prescribed Medicines (ACPM). Dr Mackay informed the Tribunal that she had removed this sentence in anticipation of a change in the guidelines which she had partly drafted and were to come into effect at approximately the same time as Inflectra was going to be approved. She was then satisfied that no substantial risk was associated with the switching between Remicade® and Inflectra and therefore removal of this sentence would be consistent with the new guidelines. Dr MacKay described the PI as a draft document subject to change until the approval letter was signed.

    Cross-examination by Mr Kirk

  31. Most of this cross-examination was subject to the Confidentiality Order and the remainder was non-contributory in that, it essentially confirmed previous evidence or went to dates of approval of Inflectra in other countries.

    Re-examination by Mr Pizer

  32. Mr Pizer confined his re-examination to the subject of why Dr Mackay would not have included the word (Remicade®) in the first sentence under a heading entitled Clinical trials conducted with the reference medicine (Remicade®). Dr Mackay considered the insertion of (Remicade®) in Dr McEwen’s review decision as open to being interpreted as promotional, particularly as the name Remicade® was repeated. This was contrary to TGA policy not to refer to reference medicines by their trade name unless there was good reason to do so.

    Exhibits to Dr MacKay’s affidavit

  33. Dr Mackay’s first affidavit contained several exhibits numbered KM1 to KM3.

  34. Exhibit KM1 is The Prescription Medicine Registration Process of the TGA, September 2014 version. This is a detailed document relating to the process of assessment, addressing the so-called milestones in the regulatory phase, these being MS1 to MS8. Of particular relevance is Phase 6, relating to Expert advisory review by the Advisory Committee on Prescription Medicine and The Pharmaceutical Subcommittee. The Advisory Committee on the Safety of Medicines is also involved where necessary. Throughout, provision is made for the applicant/sponsor to review all evaluation reports and to provide new data in support of their application.

  35. Exhibit KM2 is the December 2015 version of the document entitled Regulation of Biosimilar Medicines. This includes the definition of a biosimilar medicine relating to medicine classifications elsewhere as:

    ·similar biological medicinal products (European Union)

    ·similar bio-therapeutic products (World Health Organisation)

    ·subsequent entry products (Canada)

    ·follow-on products.

    It is also states that both the biosimilar and its reference medicine will have the following similar characteristics:

    ·physicochemical

    ·biological

    ·immunological

    ·efficacy and safety.

  36. The TGA has adopted the European guidelines. These have been regularly updated between 2003 and 2012. Particular reference is made to the extrapolation of indications for the use of biosimilar medicines, once more referring to the European guidelines. It is TGA policy as outlined in KM2 to not use non-proprietary names to identify biosimilar and reference materials. Use of the biological name of the active ingredient/s is to be used.

  37. The Exhibit KM3 is entitled:

    FORM FOR PROVIDING PRODUCT INFORMATION FOR A RESTRICTED MEDICINE OR OTHER MEDICINE IN RELATION TO WHICH THE SECRETARY REQUIRES PRODUCT INFORMATION TO BE PROVIDED

    This form was approved under subsection 7D(1) of the Act and must accompany the application in accordance with paragraph 23(2)(ba). The exhibit outlines the requirements in detail. The precautions which are listed as requirements are those arising in relation to fertility, pregnancy, lactation, paediatric use, use in the elderly, genotoxicity and carcinogenicity.

    TRIBUNAL’S DELIBERATIONS AND DECISION

  38. As previously stated, the Tribunal handed down an oral decision on 20 June 2017, having received and considered submissions from all parties addressing the current and past versions of the Act, the amendments contained within the Therapeutic Goods Amendment (2013 Measures No. 1) Act 2014 and the relevant EM for the amending Act. The particular sections of the Act in dispute with respect to interpretation are ss 25(3), 25AA(1), 25AA(1A), 25AA(4) and 25AA(4A).

  39. The overriding provision of the Act is s 4 which relevantly states, in part:

    (1)The objects of this Act are to do the following… :

    (a)provide for the establishment and maintenance of a national system of controls relating to the quality, safety, efficacy and timely availability of therapeutic goods…

    The supremacy of this provision relates to both the application and interpretation of the Therapeutic Goods Act 1989. The Tribunal must make its decision in accordance with the High Court of Australia authority in relation to statutory interpretation, this having been crystallised in Project Blue Sky Inc v Australian Broadcasting Authority (1998) 194 CLR 355 as mandating a contextual approach and the acceptance that the provisions are intended to give effect to harmonious goals.

  1. The EM indicates that the proposed amendment detailed in s 25AA(1) was intended  to clarify the Secretary’s power to approve product information for medicines requiring provision of a PI when a decision had been made to register the goods. The proposed s 25AA (1A) also required that the Secretary must not approve the product information unless satisfied that the latter reflects the basis on which the Secretary decided to register the goods under s 25(3). The EM states that these changes in relation to s 25AA(1A) were intended to indicate the importance of product information being consistent with the basis on which the Secretary made the decision to register the medicine. It is clear that the purpose was to avoid inconsistency and contradiction.

  2. The EM acknowledged that product information is an integral component of the decision to register the medicine and essentially underpins the registration decision, particularly with respect to the quality, safety and efficacy of the medicine. The EM states that the product information is reviewed by the Secretary while the application for registration of the medicine is being evaluated and may be the subject of discussions with the applicant at that time.

  3. The EM summarises the proposed s 25AA(1A) and s 25AA(4A) as being intended to capture current practice in the approval of PI by the Secretary under the Act. This clearly refers to the existing procedures undertaken by the TGA in its assessment of the PI data.

  4. The Tribunal notes that s 25AA(4) permits the Secretary to vary approved PI for medicines that are already approved and entered in the Register. This the Tribunal perceives as relating purely to the reference biosimilar biological medicine (here Remicade). It does not permit such changes to applications for registration prior to a decision being made to effect registration and entry of the approved goods in the Register.

  5. In light of the EM statement regarding the capturing of current practice, the Tribunal determined to hear from Dr Mackay in order to ascertain the current practice for approval. Having heard Dr Mackay’s evidence and taken into account the contents of her affidavit and the exhibits thereto, the Tribunal is fully satisfied that the procedures and process followed by TGA in assessing the proposed PI is rigorous, scientifically based, has accessed expert opinion both internal and external on several occasions and has complied with its established and published regulations (Exhibits KM1-KM3).

  6. The Amended Act as it currently stands is mandatory in terms of s 25(3) in that the Secretary must decide to register the goods or not. Sections 25AA(1)(a) and (b) also provide that the Secretary must approve the PI if they decide to register the goods. All of the evidence and submissions of the Minister and the applicant point to the PI as being the practical basis for registration, as is acknowledged in the EM. The Tribunal determines that the two are indivisible, or to use the terminology of the applicant undivorceable, as it is clear  to the Tribunal, that it is the PI that is the major contributory factor forming the basis of the decision to register a biosimilar medicine while acknowledging the lesser but vital input from experts, clinicians, the ACM and other advisory bodies and the PI of the reference medicine as updated.

  7. The Tribunal accepts that s 25AA(1A) mandates that the Secretary must not approve the PI unless they are satisfied that it reflects the basis on which the Secretary decided to register the goods. Given the duration of the evaluation and assessment procedure, the ongoing consultation with the sponsor and referral to various experts and advisory committees, the possibility that the PI does not reflect the basis of the decision to register the goods is extremely remote.

  8. The Tribunal has not been able to discern any provision of the Act that provides that on review under s 60 the Secretary can change the wording and effect of the PI following such an application. Such reviews may require or be accompanied by information in support of the request and the Tribunal has no knowledge of any such information having been provided. Section 60 states that the decisions for which for internal review may be sought includes a decision under Part 3-2A (biologicals). Section 60A(2) empowers the Minister to reconsider an application by an affected party if new information is provided or alternatively remit the matter for reconsideration.

  9. The actual decision to register Inflectra was not challenged. The Act does not provide for review specifically in relation to PI data. The s 25AA(4) variations to product information relate only to already registered therapeutic medicines. This of course would only apply to the reference medicine Remicade®. There is reference in the Act stating that, on review, the Secretary can change the PI should new information be provided. There has been no suggestion that Janssen provided any such information.

  10. While not the subject of any submissions before the Tribunal, the Tribunal is concerned by the substitution by Dr McEwen in the PI (Exhibit OP1) of Dr Mackay’s entry stating:

    INFLECTRATM (Infliximab) is an approved biosimilar to the reference product REMICADE® (Infliximab). Comparability and safety, efficacy and quality between INFLECTRATM and REMICADE® has been established.

    has been changed to:

    INFLECTRATM (Infliximab) is an approved biosimilar to the reference product REMICADE® (Infliximab). The comparability of INFLECTRATM with the reference medicine REMICADE® (Infliximab) has been demonstrated with regard to particular physiochemical characteristics and efficacy and safety outcomes. (See PHARMACOLOGY and CLINICAL TRIALS).

    The Tribunal considers the substituted paragraph is at odds with the definition of an approved biosimilar as it restricts the comparability of Inflectra to Remicade® to particular physiochemical characteristics. Such a restriction is in conflict with the TGA’s accepted definition of a biosimilar therapeutic medicine as determined by the adoption of those of the European Medicines Agency, the European Mutual Agreements and also the Food and Drug Administration (FDA) of the United States of America.

  11. Once a therapeutic medicine and in this instance a biosimilar medication has been approved and accepted for registration the TGA is required to add that particular biosimilar medication to its Register of Approved Therapeutic Medicines and to publish an updated Register once every 12 months. The producers/sponsors of such registered bio‑chemicals are required as a condition for registration to report any changes to their PI’s as registered and in accordance with s 9D(3A) or (3AA) and to the Tribunal’s knowledge, most would accord with s 9D(3A)(b).

  12. Thus, there remains an ongoing requirement for the manufacturer of any biosimilar medicine listed on the Register to update the TGA in relation to any changes in the product information which would, among other data, reflect the results of any further clinical trials, adverse side effect reports and new contra-indications for the particular medicine’s use. These are clearly required for the ongoing monitoring of the quality, safety and efficacy of any therapeutic medicine.

  13. The Tribunal has set aside the decision under review on the basis that the decision of Dr McEwen with respect to the product information and the alterations he introduced was ultra-vires as Dr McEwen exceeded the power invested in him by the Act. The matter is remitted to the Minister for reconsideration.

I certify that the preceding 107

(one hundred and seven) paragraphs are a true copy of the reasons for the decision of: Miss E A Shanahan, Member

............[sgd]............................................................

Associate

Dated: 18 December 2017

Dates of hearing: 19 and 20 June 2017
Counsel for the Applicant and Other Party No 2:

Mr Jeremy Kirk SC, Mr Henry El-Hage

Solicitor for the Applicant and Other Party No 2:

Mr Jonathan Kelp, Minter Ellison

Counsel for the Respondent:

Mr Jason Pizer QC, Ms Kathleen Foley

Solicitor for the Respondent:

Mr Kenneth Teoh, Department of Health

Counsel for Other Party No 1:

Mr Stephen Free
Solicitor for Other Party No 1: Ms Sheena McKie, Clayton Utz

Key Legal Topics

Areas of Law

  • Administrative Law

  • Statutory Interpretation

Legal Concepts

  • Judicial Review

  • Statutory Construction

  • Jurisdiction

  • Procedural Fairness

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