Pharmacor's submissions
53 Pharmacor's principal submission is that GSK has not demonstrated the requisite reasonable belief that it may have a right to obtain relief against Pharmacor.
54 First, it is said that GSK has led no evidence to establish the existence of that belief or its reasonableness. It says that GSK relies upon mere speculation or conjecture. In particular, it is said that there is no evidence to support the proposition that Pharmacor has made or will make the various representations or statements alleged by GSK. Nor is there any evidentiary basis for GSK's assertion that those representations or statements, if made, would be false or misleading. It is said that no evidence has been led, for example, to attempt to establish that the Pharmacor Products are not in fact "bioequivalent to", "interchangeable or substitutable with" or "as good as" the GSK products as alleged. It is said that the Patent does not provide any such evidence. Further, it is said that there is no evidence that a tablet falling outside the parameters claimed in the Patent would, when compared with a tablet falling within the claims, make any relevant material difference when given to a patient. It is said that GSK's case is based on assertion, with no evidence to incline the mind in favour of any right to relief.
55 Pharmacor has also filed substantial affidavit material seeking to justify the merits of its argument that GSK has no claim against it. Although interesting, I am not at this stage dealing with the merits of any claim or Pharmacor's defences thereto other than to the extent of determining whether GSK has a reasonable belief that it may have a right to obtain relief. Pharmacor has also gone so far as to refer to some of the very material it has placed before the TGA. Of course, GSK has no access to this at this stage; this material is what is being sought by this application.
56 There are a number of responses to Pharmacor's primary contention as follows.
57 At the core of Pharmacor's position is the submission that GSK has not demonstrated any reasonable belief that the Pharmacor Products are not "bioequivalent" to Panadol Osteo in relation to how the TGA has used the concept of "bioequivalent". I accept this submission. Although there is some difference in the material as to what is meant by "bioequivalent", it seems to me that in terms of how the TGA has used that term, there is no proper basis for contending that the Pharmacor Products have not properly or accurately been assessed so as to accord with how the TGA has used that characterisation.
58 GSK has made a number of submissions suggesting that "bioequivalence" can be differently assessed and characterised. Indeed, it has gone so far as to inject into that characterisation concepts that relate to therapeutic equivalence. But even accepting such submissions, it does not show any basis for saying that the TGA's characterisation of bioequivalence between Panadol Osteo and the Pharmacor Products is not on all fours with how the TGA has used such a concept.
59 Second, it is said that GSK can have no reasonable belief that it may have the right to obtain relief from Pharmacor in respect of representations alleged to have been made to the TGA. It is said that as part of its application to the TGA, Pharmacor submitted relevant data which was evaluated and assessed by the TGA. It is said that the TGA made its own assessment of that data and determined to its satisfaction that the Pharmacor Products were bioequivalent to Panadol Osteo. It is said that in doing so, the TGA performed its statutory function. It is said that there is no evidence at all of any misrepresentation or material non-disclosure made by Pharmacor to the TGA or any reliance thereon by the TGA.
60 I accept this submission. The general process followed by the TGA appears to be as follows.
61 The TGA publishes guidelines on its website at https://www.tga.gov.au/industry to assist sponsors to prepare applications. In respect of OTC medicines these guidelines are the Australian Regulatory Guidelines for OTC Medicines (ARGOM).
62 The ARGOM provides information as to the registration process applicable to OTC medicines, including:
(a) TGA regulatory requirements for the preparation and submission of an application and the data required in support of an application;
(b) the TGA's pre-market evaluation and assessment processes, including:
(i) the rounds of assessment undertaken by the TGA;
(ii) the use of expert statutory scientific advisory committees;
(iii) the issuing by the TGA of evaluation/assessment reports of quality, nonclinical and clinical evaluators as required;
(iv) the processes by which the TGA can seek further information from applicants (referred to as "section 31 requests") and applicants' responses;
(v) the processes involved in the TGA's making a request for expert advisory committee review and advice;
(c) the Secretary's determination of whether to approve or reject the application; and
(d) the Secretary's finalisation of the decision, including notifying the applicant of the Secretary's decision and entering the goods on the ARTG once regulatory requirements are met.
63 In the course of evaluating an application for registration of a generic medicine, including evaluating the supporting data to determine if bioequivalence of the medicine has been demonstrated with a reference medicine, the Secretary may seek independent expert advice to assist in his or her evaluation from a number of statutory advisory committees (which are established under the Therapeutic Goods Regulations 1990 (Cth)). The relevant committee from which the TGA can seek independent expert advice in evaluating an application in the case of OTC medicines is the Advisory Committee on Non-prescription Medicines (ACNM). This committee is comprised of experts in pharmacy, medicine (including in particular fields of medicine), clinical pharmacology, drug quality (including bioavailability and bioequivalence), preclinical toxicology, clinical studies, drug safety and drug development. The ACNM can also enlist assistance and advice from sub-committees. It is not apparent that the ACNM met or reported on the Pharmacor Products.
64 On completion of an evaluation, the Secretary decides whether to accept or reject the application for registration, based on evaluation of the information in the applicant's submission, including the data in support of that submission, any advice received from advisory committees and other information obtained during the evaluation phase. In the case where product information is required to be submitted for evaluation by the Secretary in relation to a medicine, the Secretary is required to evaluate that product information and notify the applicant of the approved product information in respect of that product when the product has been approved for registration.
65 Pharmacor has asserted that in accordance with these procedures, the TGA evaluated Pharmacor's application and assessed the data submitted by Pharmacor. It is said that the TGA made its own assessment and determined to its satisfaction that the Pharmacor Products were bioequivalent to Panadol Osteo, applying the applicable regulatory standard.
66 In my view, there is a doubt in the material as to what process was in fact followed by the TGA in evaluating the Pharmacor Products. The material before me suggests that the TGA may not have referred the application for registration to the relevant committee/subcommittee(s). Nevertheless, even if it did not, any such deficiency (if there be one) does not provide a reason to believe that there has been any relevant misrepresentation or non-disclosure to the TGA by Pharmacor or any mischaracterisation of the Pharmacor Products as being bioequivalent to Panadol Osteo in the sense of how that term has been used by the TGA.
67 Pharmacor generally stresses the independence of the TGA in its assessment. But accepting that to be so, the TGA is nevertheless reliant upon accurate and complete information from Pharmacor. But in my view there is no reason to doubt that Pharmacor has provided such accurate information to the TGA as required of Pharmacor in order for the TGA to carry out an adequate assessment of bioequivalence.
68 Third, Pharmacor says that GSK can have no reasonable belief that it may have the right to obtain relief from Pharmacor in respect of representations made to the Pharmaceutical Evaluation Branch of the Department of Health (PEB). It is said that this is because the relevant representation as to bioequivalence was made by the TGA (not Pharmacor) to the PEB and that such a representation was true. It is said that the representation was that the TGA approved the Pharmacor Products as being bioequivalent to Panadol Osteo, which it in fact did.
69 Again, there was little dispute as to the procedures followed.
70 On 25 August 2014, Pharmacor applied to the PEB for listing of the Pharmacor Products on the PBS pursuant to the relevant provisions of the National Health Act 1953 (Cth). That application included a copy of a notification by the TGA that the TGA had determined to its satisfaction that the Pharmacor Products were bioequivalent to Panadol Osteo.
71 The website of the Department of Health, Pharmaceutical Benefits Scheme explains that the TGA's notification concerning bioequivalence is required by the PEB:
The following information must be received by the Listing Unit ... :
Brand Equivalence Statement (applies to New Brands only). New brands must be listed with an equivalence indicator. In order for a brand equivalence indicator to be included in the entry for the new brand, it is the sponsor's responsibility to request a statement from the TGA indicating that it is appropriate for an equivalence indicator to be shown in the PBS Schedule, and against which other brands. This advice must be received by the Listing Unit by the deadline. It is suggested the statement be requested from the TGA towards the end of the evaluation process to ensure that the TGA has sufficient time to provide the advice prior to the listing deadline.
72 It is apparent that any notification or representation made as to bioequivalence to the PEB was made by the TGA rather than Pharmacor. There is no evidence that the TGA was the cat's paw of Pharmacor. Further, there is no evidence that the TGA made any representation to the PEB of anything other than the accurate statement that the TGA had determined to its satisfaction that the Pharmacor Products were bioequivalent to Panadol Osteo.
73 In my view, there is no basis for saying that GSK might have a claim against Pharmacor in relation to any representation made to the PEB. Further, any representation made by the TGA to the PEB was accurate.
74 Fourth, it is said that even if Pharmacor had made representations to the TGA or the PEB as alleged by GSK (and assuming they were misleading) then those representations were not made "in trade or commerce" so as to attract the operation of ss 18 or 29(1)(a) or (1)(g) of the ACL.
75 Given the conclusions set out above, strictly it is unnecessary to deal with this aspect. But if I am wrong, I also accept Pharmacor's submissions in this respect in any event.
76 Concrete Constructions (NSW) Pty Ltd v Nelson (1990) 169 CLR 594 (Concrete Constructions) establishes that the phrase "in trade or commerce" refers not to "the immense field of activities" in which corporations may engage in the course of carrying on some overall trading or commercial activity, but rather to the central conception of trade or commerce (see at 603-604 per Mason CJ, Deane, Dawson and Gaudron JJ).
77 Generally, representations made to statutory authorities as required by legislation in order to satisfy a statutory condition or to "procure" an exercise of statutory power are outside the scope of "in trade or commerce". They are not of themselves in the course of a trading or commercial relationship or bear a trading or commercial character. The relationship is rather "a relationship between a regulator and a regulated industry or business" (Village Building Co Ltd v Canberra International Airport Pty Ltd (2004) 139 FCR 330 at [51] per French, Sackville and Conti JJ; Glueck v Stang (2008) 76 IPR 75; [2008] FCA 148 at [32]-[33] per Lindgren J; Interpharma Pty Ltd v Commissioner of Patents (2008) 107 ALD 342; [2008] FCA 1283 at [14] per Sundberg J and Gold & Copper Resources Pty Ltd v Newcrest Operations Ltd [2013] NSWSC 281 at [109], [116]-[118] per Stevenson J).
78 GSK asserts that such authorities do not deny its argument that any representations made by Pharmacor to the TGA or the PEB were "in trade or commerce". It says that the above cases are distinguishable. GSK says that in the present case, Pharmacor's representations made to the TGA and the PEB were a necessary part of its ultimate objective to market and supply its product for profit to pharmacists, medical practitioners and the ultimate end user. But even accepting this to be correct, that does not establish that the conduct of Pharmacor vis a vis the TGA was "in trade or commerce" as such; likewise in terms of the conduct of Pharmacor vis a vis the PEB. GSK relied upon some observations in Brown v Riverstone Meat Co Pty Ltd (1985) 60 ALR 595 at 607 per Wilcox J, but in my view such observations are not of assistance; they pre-date Concrete Constructions.
79 GSK has not established that it is reasonably arguable that Pharmacor's conduct vis a vis either the TGA or the PEB was "in trade or commerce". Alternatively expressed, GSK has not established a reasonable belief as to this element of any claim based under ss 18 or 29(1)(a) or (1)(g) of the ACL in relation to any alleged representations made by Pharmacor to the TGA or the PEB.
80 Fifth, it is said that GSK has no reasonable belief that it may have the right to obtain relief from Pharmacor in respect of its promotion of the Pharmacor Products to pharmacists and/or consumers in contravention of ss 18 and 29(1)(a) and (1)(g) of the ACL. It is said that the evidence led by Pharmacor establishes that no false or misleading representations will be made to pharmacists or consumers, and that GSK has no basis for suggesting otherwise.
81 It is this aspect of the matter that in my view GSK has made out. GSK has a reasonable belief as to a potential claim based upon the half-truth scenario or misleading or deceptive conduct partly constituted by silence or omission. I reject Pharmacor's submissions on this aspect.
82 GSK says that Pharmacor has or will promote the Pharmacor Products as being "bioequivalent to", "interchangeable or substitutable with" or "as good as" the GSK Products or similar statements suggesting such a comparison; it is said that such statements will or are likely to contravene ss 18 and 29(1)(a) and (1)(g) of the ACL.
83 It is appropriate to summarise the evidence as to how Pharmacor intends to promote and supply the Pharmacor Products.
84 Pharmacor says that the only statements that it will make to pharmacists and consumers in supplying and promoting the Pharmacor Products are to the effect that the TGA has approved these products as being bioequivalent to Panadol Osteo and that the PEB has approved the Pharmacor Products to be interchangeable or substitutable with Panadol Osteo. Let me elaborate.
85 First, the Pharmacor Products are to be marketed in packaging which has been approved by the TGA and submitted by Pharmacor as part of its application for PBS Listing. It is said that there will be nothing on the packaging of the Pharmacor Products which makes any reference to the Pharmacor Products' bioequivalence to Panadol Osteo.
86 Second, the Pharmacor Products will be supplied to pharmacists together with product information approved by the TGA under s 25AA of the Therapeutic Goods Act 1989 (Cth).
87 Third, if any consumer medicine information is to be supplied inside any pack of the Pharmacor Products, it will make no reference to the Pharmacor Products' bioequivalence to Panadol Osteo.
88 Fourth, apart from the statements referred to in [84] and [89], Pharmacor does not propose to promote the Pharmacor Products:
by referring in general terms to the "bioequivalence", "equivalence" or "similarity" of the Pharmacor Products to Panadol Osteo (or use similar expressions);
by referring in general terms to the "interchangeability" or "substitutability" of the Pharmacor Products to Panadol Osteo (or use similar expressions); or
by claiming or asserting that the Pharmacor Products are "the same as", "identical to" or "as good as" Panadol Osteo (or use similar expressions).
89 Fifth, Pharmacor proposes to ensure, in all marketing and promotional material for the Pharmacor Products, that:
any reference to "bioequivalence" of the Pharmacor Products to Panadol Osteo, is made using the phrase "approved by the TGA as bioequivalent to PANADOL OSTEO" or a similar expression referring to its correct regulatory status; and
any reference to "interchangeability" or "substitutability" of the Pharmacor Products for Panadol Osteo is made using the phrase "listed on the PBS as interchangeable with or substitutable for PANADOL OSTEO" or a similar expression referring to its correct PBS listed status.
90 It is said that such statements will not only be literally true, but are consistent with pharmacists' understanding in respect of "bioequivalence", "interchangeability" and "substitutability".
91 Further, the evidence of Dr Walters was to the effect that Australian pharmacists:
understand that pharmaceutical products listed on the PBS as being equivalent to another brand include a "brand equivalence" indicator (being superscript 'a' or 'b' located immediately before the brand names of a particular strength of an item);
understand that in the context of a medicine listed on the PBS as interchangeable with another brand, an 'a' flag indicates that the TGA has approved the medicines as being bioequivalent or therapeutically equivalent;
understand that in order for a new brand to be listed on the PBS with a brand equivalence indicator, the TGA must have provided a statement to the PBS that it has determined that the products are bioequivalent;
understand that if a new brand of a medicine is marked as brand equivalent on the PBS against another medicine, the TGA has assessed and approved the new brand as equivalent to the brand against which the equivalence indicator is applicable; and
identify alternative generic brands for a medicine when dispensing medicines by conducting searches using prescribing software, which contains information as to the brands listed on the PBS that have a brand equivalence indicator indicating that the brands can be interchanged.
92 Let it be accepted that the proposed promotion by Pharmacor of the Pharmacor Products to pharmacists and consumers will involve references to "bioequivalence" between the two products using the phrase "approved by the TGA as bioequivocal to Panadol Osteo" and references to brand equivalence. Let it also be assumed that such statements are literally true in the sense of being accurate descriptions of the TGA's and PEB's descriptions (as distinct from the objective truth of such characterisations). Yet that does not deny the realistic scenario of misleading or deceptive conduct or false representation being constituted by a half-truth or by omission.
93 First, there are at least two potential classes to consider, viz, pharmacists and the end users or consumers. End users or consumers may take such a statement "approved by the TGA as bioequivocal to Panadol Osteo" as meaning that the Pharmacor Products are interchangeable or substitutable with Panadol Osteo. They may take such a statement to mean or imply that the Pharmacor Products deliver all the same benefits as Panadol Osteo. They may not understand fully what "bioequivocal" entails and any imprecision in that concept, let alone know how the TGA have used that concept. They may readily conclude complete interchangeability, substitutability and identical benefits without any discrimination whatsoever. Moreover, such promotions and understanding may be fortified by the imprimatur and gravitas of the phrase "approved by the TGA as bioequivocal …". Further, pharmacists may understand the subtlety of such a phrase in terms of how the TGA have used the phrase "bioequivocal", but they may not. Alternatively, they may gloss over relevant distinctions. As Dr Walters observed:
40. In my practice as a pharmacist, I identify alternative generic brands for a medicine when filling prescriptions by conducting searches using prescribing software, which contains information as to the brands listed on the PBS that have a brand equivalence indicator indicating that the brands can be interchanged. This is a surrogate for consulting the PB schedule itself. If I have time (which is not likely) I can also identify alternative brands of medicines that are bioequivalent by conducting a search on the PBS website at http://www.pbs.gov.au/pbs/home, by active ingredient or original brand, then looking for 'a' or 'b' in the "Available brands" field. I understand that brands marked 'a' can be substituted for others marked 'a', and those marked 'b' can be substituted for others marked 'b' but brands marked 'a' cannot be substituted with brands marked 'b'. Based on my interactions with my colleagues who are community pharmacists, my knowledge and experience of prescribing practices and my observation of the practices of other community pharmacists, I understand that other community pharmacists in Australia identify alternative generic brands of a medicine in the same way as I have described above.
41. In order for a new brand to be listed on the PBS with a brand equivalence indicator in the entry on the PB Schedule, the TGA must have provided a statement to the PBS that it has determined that the products are bioequivalent. This requirement is set out on the PBS website at http://www.pbs.gov.au/info/industry/listing/elements/listing-unit-requirements, a copy of which is annexed at Annexure SMW-7.
42. Therefore, if a new brand of a medicine is marked as brand equivalent on the PBS against another medicine, I understand that the TGA has approved the new brand as equivalent to the brand against which the equivalence indicator is applicable. Based on this approval, I dispense medicines that are brand equivalent (provided that the patient consents and the prescriber has not annotated the prescription 'Brand substitution not permitted') and believe there is no significant difference in safety or efficacy between the brands. Based on my interactions with my colleagues who are community pharmacists, my knowledge and experience of dispensing practices and my observation of the practices of other community pharmacists, I understand that other community pharmacists in Australia identify interchangeable generic brands of a medicine in the same way.
Accordingly, once there is this "brand equivalence", flowing from the TGA's characterisation of bioequivalence, pharmacists are likely to treat the products as, for all relevant purposes, the same and to supply or promote them to consumers accordingly.
94 Second, although such representations or statements may not appear on actual packaging, nevertheless broader promotions and marketing material are likely to contain such representations or statements. Further, the material suggests that promotional material may either be targeted directly at the end user or targeted at pharmacists who will then so promote to the end user. There is another class of persons being medical practitioners who may be the potential targets of such representations, but I do not need to consider them further for present purposes.
95 In terms of looking at potential classes of persons and how they might understand the relevant promotional material, as I say the intended audience or potential classes are either pharmacists or actual or potential consumers of the Pharmacor Products. Where there is a dispute as to the effect of conduct on a class of persons, such as consumers who may range from the gullible to the astute, what is considered is whether an ordinary and reasonable member of that class would be or was likely to be misled or deceived (Google Inc v Australian Competition and Consumer Commission (2013) 249 CLR 435 at [6]-[9] per French CJ, Crennan and Kiefel JJ). Further, in considering the hypothetical ordinary and reasonable member of the relevant class, one considers the dominant message conveyed (Australian Competition and Consumer Commission v TPG Internet Pty Ltd (2013) 250 CLR 640 at [20], [40] and [45] per French CJ, Crennan, Bell and Keane JJ). Further, where general injunctive relief is being sought, all that may be required to be shown is that the relevant statement has a tendency to lead persons of the relevant class into error; contrastingly, if an individual damages claim is being made, causation, including reliance questions, needs to be specifically addressed. Moreover, the question is whether there is a real rather than a remote possibility of the member of the relevant class being misled or deceived. For completeness, I have not separately addressed whether the proposed statements made or to be made by Pharmacor are fact or opinion, putting to one side the functional utility of such a division (cf Forrest v Australian Securities and Investments Commission (2012) 247 CLR 486 at [38] per French CJ, Gummow, Hayne and Kiefel JJ). Pharmacor did not advance any separate argument based upon any such division.
96 Third, the potential half-truth scenario or misleading or deceptive conduct by omission or silence might arise in circumstances where:
the products are "bioequivalent" in one sense of that term, but not "bioequivalent" in another sense of that term;
the products are "bioequivalent" whatever the sense of the term, but are not completely interchangeable or substitutable because they each deliver different therapeutic or other benefits;
the products are "brand equivalent" in one sense of that term, but not "brand equivalent" in another sense of that term;
the products are "brand equivalent" whatever the sense of the term, but are not completely interchangeable or substitutable because they each deliver different therapeutic or other benefits.
97 In terms of principle:
One looks at the relevant course of conduct as a whole in light of the surrounding facts and circumstances (Butcher v Lachlan Elder Realty Pty Ltd (2004) 218 CLR 592 at [109] per McHugh J (dissenting in the result but not the principle)).
Silence is to be assessed as a circumstance like any other (Demagogue Pty Ltd v Ramensky (1992) 39 FCR 31 at 32 per Black CJ).
A practical approach may be to consider whether there is a reasonable expectation of disclosure as an aid to the necessary factual enquiry, but this is not to be taken as any reformulation of the statutory test (Miller and Associates Insurance Broking Pty Ltd v BMW Australia Finance Ltd (2010) 241 CLR 357 at [20]-[21] per French CJ and Kiefel J).
98 Generally, there is evidence before me suggesting that the Pharmacor Products differ from Panadol Osteo, notwithstanding the TGA's ascription of bioequivalence and the PEB's ascription of brand equivalence.
99 Pharmacor has been at pains to point out that the Pharmacor Products do not infringe claim 1 of the Patent. It was not in dispute that, contrastingly, Panadol Osteo satisfies all integers of claim 1. Indeed, Pharmacor asserts that there is no material before me which suggests that GSK has a reasonable belief as to even a potential claim for infringement or threatened infringement of the Patent. But to so assert bespeaks that Pharmacor accepts that there is a difference between the Pharmacor Products on the one hand and Panadol Osteo on the other hand. But notwithstanding this, it wants to take the stance (indeed overly subtle and nuanced from GSK's perspective) that its products are "bioequivalent" and "brand equivalent" to Panadol Osteo. When pointed out that such ascriptions may conceal rather than reveal any true differences, it sought refuge in the proposition that it was using such "labels" in the sense of "as approved or used by" the TGA or the PEB. That enabled it, of course, to say that its promotions and representations to pharmacists and consumers were literally true. That may be so. But that is no answer to the half-truth scenario or misleading or deceptive conduct constituted partly by silence or omission. The question is whether GSK has reason to believe that there are arguable differences between the products such that Pharmacor's literally true representations to pharmacists and consumers may arguably amount to half-truths or misleading or deceptive conduct by omission in the context of the "positive statements". Let me address the Patent for the moment to highlight the difference in the products and also to deal with part of an alternative case put by GSK along the lines that if bioequivalence existed, then the Pharmacor Products are likely to fall within claim 1 of the Patent.
100 Pharmacor rightly points out that claim 1 of the Patent has, as integers, the immediate release phase in one layer as within a stipulated percentage range by weight of total paracetamol in admixture with a matrix forming polymer, and within another stipulated percentage range by weight of total paracetamol in like context in the sustained release phase in the other layer. Further, claim 1 stipulates that the relevant composition (the bilayer tablet having an immediate release phase of paracetamol and sustained release phase of paracetamol) is to have an in vitro paracetamol dissolution profile with certain percentage release constraints within three periods of 15, 60 and 180 minutes; the dissolution profile is to be determined using the USP type III apparatus, reciprocating basket, with 250ml of 0.1M HCl at 37C set at a cycle speed of 15 strokes/minute, although the detail thereof does not matter for present purposes.
101 Pharmacor has then drawn my attention to the only precise evidence before me concerning an analysis of the Pharmacor Products as compared with Panadol Osteo. In "Confidential Exhibit BLM-10" to the affidavit of Mr Miller affirmed 6 November 2014 (BLM-10), there is a dissolution profile comparison between the Pharmacor Products and Panadol Osteo. The in vitro testing conditions are comparable to those described in claim 1 of the Patent. Moreover, the dissolution profiles for the three periods of 15, 60 and 180 minutes referred to earlier are contained within a broader reported data set contained in BLM-10. Without unnecessary elaboration given the confidential nature of the material, it is sufficient to say that BLM-10 on its face demonstrates that the Pharmacor Products fall outside the integers of claim 1. Moreover, there is no other material before me suggesting otherwise. GSK asserts that BLM-10 only deals with one (and perhaps an out of date) batch. Be that as it may, that is the evidence. To assert potential infringement beyond BLM-10 is to engage in speculation. GSK asserts that if the TGA has found bioequivalence, then somehow infringement may be inferred. Such reasoning is speculative, in some sense it is a non-sequitur (given the different concept and ascertainment of bioequivalence), and moreover it is negated to some extent by BLM-10. Moreover, GSK previously sought and obtained documents from Pharmacor, including BLM-10, and reviewed the same prior to its letter of 10 October 2014 sent to Pharmacor seeking preliminary discovery. Its letter then made reference only to the ACL claims. One can infer that GSK took the view, having reviewed the earlier material, that a realistic potential infringement claim was not in the frame.
102 In summary, one can accept on Pharmacor's own case that the Pharmacor Products are different, in a meaningful way, from a product satisfying the integers in claim 1 of the Patent, that is, Panadol Osteo.
103 Further, notwithstanding the TGA's assessment of bioequivalence, such an assessment also does not rule out significant differences between the Pharmacor Products and Panadol Osteo.
104 The concept of "bioequivalence" as used by the TGA has a degree of imprecision and variability. One view is that the phrase may be aligned with an equivalence of "safety and efficacy", themselves imprecise concepts (see the Guidelines on efficacy and safety aspects of OTC applications published by the TGA in October 2012). Further, there may be different meanings (see for example the US FDA guidelines).
105 Further, bioequivalence is usually established using only in vitro dissolution tests. A correlation between in vitro release characterisation (established by in vitro dissolution testing) and in vivo bioavailability parameters may assist to demonstrate that in vitro dissolution testing can act as a proxy for in vivo behaviour. Nevertheless, such correlation analysis is not a necessary part of establishing bioequivalence between different products. Such bioequivalence can be established from in vitro data alone, rather than individual in vitro data for each particular product being also required to be separately correlated with in vivo bioavailability parameters for that product. But not to use in vivo analysis or secondary correlation analysis does demonstrate some fluidity in the concept of bioequivalence and may conceal different performance characteristics. There is evidence that in vitro dissolution data without more may not predict in vivo characteristics. Now there is some evidence that the TGA has received from Pharmacor some clinical studies, but their contents and how they have been used is unclear.
106 Further, two products may be treated as bioequivalent even though they differ in release controlling excipients or mechanisms if they show similar in vitro dissolution profiles. This demonstrates some fluidity in the concept of bioequivalence and may conceal different performance characteristics.
107 Further, bioequivalence usually compares the metrics and variables AUC0-t, AUC0-inf and Cmax, but as I have referred to earlier and as Mr Pascarl points out in his affidavit of 5 November 2014 at [21]-[22]:
21. However, in the case of a modified release paracetamol product, the most therapeutically important pharmacokinetic properties are not Cmax or AUC alone, rather, they are also:
(i) the time taken to reach a therapeutically active plasma paracetamol concentration of 4µg/ml or greater (that is, an indication of how quickly pain relief is provided); and
(ii) the duration of time for which a therapeutically active plasma paracetamol concentration of 4µg/ml or greater is maintained (that is, an indication of how long pain relief lasts).
22. It may be the case that the AUC of two modified release paracetamol products is the same, but the respective products':
(i) time taken to reach a therapeutically active plasma paracetamol concentration of 4µg/ml or greater; and
(ii) duration of time for which a therapeutically active plasma paracetamol concentration of 4µg/ml or greater is maintained,
are quite different.
108 Further, even accepting that only variables Cmax, AUC0-t and AUC0-inf are used, because the confidence intervals used are at the 90% level, there can be considerable width in the range permitted of these variables, but nevertheless still establishing bioequivalence. As Mr Pascarl points out, "the ratio of test to reference compound primary pharmacokinetic … variables… lies within the range of 0.8 to 1.25…".
109 Further, bioequivalence may not demonstrate therapeutic equivalence for the reasons explained by Mr Pascarl, although I accept that there is a debate in the evidence as to this.
110 Generally, GSK's position is that notwithstanding the ascriptions of "bioequivalence" and "brand equivalence" by the TGA and PEB respectively and given that Panadol Osteo falls within claim 1 of the Patent and the Pharmacor Products may not, there is at least a reasonable belief to the effect that:
the products may have different clinical effects;
different release profiles between the different products may result in different pain relief effects.
111 Further, Mr Pascarl gave evidence based upon information from Mr Peter Thanopoulos, Director of Regulatory Affairs and Quality at GSK, that:
7. If a bi-layer tablet containing 665mg of paracetamol split 50-50 between an immediate release formulation layer and a sustained release formulation layer has an in vitro dissolution profile which over an initial time period releases a greater amount of paracetamol than either PANADOL OSTEO or than the dissolution profile parameters in claim 1 of the Patent, then I would expect that such a tablet would be unlikely to provide up to 8 hours of pain relief (like PANADOL OSTEO) because so much paracetamol would be released initially (when compared to PANADOL OSTEO or the parameters in claim 1 of the Patent) and a relatively smaller amount of paracetamol would be available to the patient during the latter part of the 8 hours.
8. Conversely, if such a tablet has an in vitro dissolution profile which over an initial time period releases a lesser amount of paracetamol than either PANADOL OSTEO or than the dissolution parameters in claim 1 of the Patent, then I would anticipate that such a tablet would not provide such rapid onset of pain relief as PANADOL OSTEO.
112 Now a query was raised as to whether this was borne out by other evidence before me. It is inappropriate and unnecessary to elaborate further. It suffices to say that this may be a triable issue. But at present I only need to consider whether there is the requisite reasonable belief. Pharmacor made the point that Mr Pascarl's evidence is hearsay and that Mr Thanopoulos is less expert than Dr Walters. But all of that goes to weight rather than to negate any reasonable belief.
113 The specification of the Patent also demonstrates that there can be bioequivalence between two products and yet there can be different pharmacokinetic properties. In the discussion of example 2, there was bioequivalence with respect to AUC, yet significant differences in Cmax between the products, differences in the rates of attainment of therapeutic serum concentrations and periods of maintenance of mean serum levels. In the discussion of example 3, there was bioequivalence with respect to AUC, yet significant differences between the variables for each product concerning Cmax, Cmin and the fluctuation index. Interestingly, in discussing example 3 there was also a discussion of Tylenol Extended Relief, being a 650mg bilayer sustained release tablet (see also pp 1-2) where there were equal amounts of paracetamol in an immediate release layer and a sustained release layer. A steady state biostudy conducted for Tylenol showed a higher fluctuation index than for the sustained release tablet of formulation D; if one infers that the products were bioequivalent in one sense, which seems reasonable, nevertheless they may have different fluctuation indexes. The FI metric is important; a low FI number (i.e. < 1) is considered a safer product. I have been elliptical in how I have expressed this as I have sought to avoid publishing confidential information about the Pharmacor Products.
114 In summary, in my view GSK has a reasonable belief that Panadol Osteo has different therapeutic effects to the Pharmacor Products. If there are such differences, then it seems to me that the promotion and representations proposed to be made by Pharmacor to pharmacists and consumers may mislead by just making the literally true statements of "bioequivalence as approved by the TGA" or "brand equivalence as approved", without disclosing relevant differences. Pharmacor cannot hide behind the TGA's or PEB's labels or ascriptions, particularly as Pharmacor initiated or procured them. Moreover, the apparent objective of Pharmacor is to use these equivalence labels to compete with GSK and to gain market share at GSK's expense. Pharmacor no doubt wants to tread the fine line of saying that there is bioequivalence but no infringement of the Patent. It may be correct, but that does not deny the force of GSK's point concerning the half-truth scenario. Finally, no point was taken on any entitlement to relief (in terms of injunctive relief) if the half-truth scenario was established. In my view r 7.23(1)(a) has been established in relation to such a potential claim.