Pfizer Canada Inc. v. Apotex Inc., 2002 FCT 498

Date: 20020503

Docket: T-2282-01

Neutral citation: 2002 FCT 498

Ottawa, Ontario, this 3rd day of May, 2002

PRESENT:      THE HONOURABLE MR. JUSTICE JOHN A. O'KEEFE

BETWEEN:

PFIZER CANADA INC.

and PFIZER INC.

Applicants

- and -

APOTEX INC. and

THE MINISTER OF HEALTH

Respondents

REASONS FOR ORDER AND ORDER

O'KEEFE J.

[1]                 This is a motion for an order pursuant to subsection 6(7) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, as amended (the "NOC Regulations") requiring Apotex Inc. "(Apotex") to produce samples of bulk azithromycin used in Apotex' azithromycin tablets, together with samples of such tablets. The applicants further seek production of Apotex' Abbreviated New Drug Submission ("ANDS") and Drug Master File.

Background

[2]                 By letter dated November 12, 2001, Apotex provided a notice of allegation ("NOA") pursuant to the NOC Regulations in respect of azithromycin tablets for oral administration in strengths of 250 mg. In the NOA, Apotex alleged, inter alia, that no claim for the medicine itself and no claim for the use of the medicine in Canadian Patent No. 1,314,876 (the "‘876 patent") would be infringed by the making, constructing, using or selling by Apotex of its azithromycin tablets.

[3]                 The applicants own the ‘876 patent, which claims exclusive rights to the product crystalline azithromycin dihydrate (the "dihydrate"), certain methods to prepare that product, and a pharmaceutical composition containing that product.

[4]                 In the NOA, Apotex alleges that its tablets will contain azithromycin but will not contain the dihydrate.

[5]                 Apotex has advised the applicants that its tablets will contain azithromycin isopropanolate monohydrate, which is also known as azithromycin monohydrate isopropanol clathrate (the "monohydrate").

[6]                 Apotex has filed patent application 2,245,398 (the "‘398 application") which discloses a method for preparing the monohydrate.

[7]                 The applicants attempted to follow the teachings of the ‘398 application, preparing a sample of the monohydrate. The applicants provided evidence that their sample of monohydrate was composed of 13% of the dihydrate. The applicants proffered further evidence that after a period of 12 months, some of the monohydrate sample had converted to the dihydrate such that the sample then comprised 43% of the monohydrate and 57% of the dihydrate.

[8]                 The applicants seek production of samples of the Apotex azithromycin product to determine if the azithromycin tablets do indeed contain the dihydrate product that is claimed in the ‘876 patent.

[9]                 The applicants further seek the production of the portions of the Apotex ANDS that detail:

1.          The process to make bulk azithromycin;

2.          The tableting process for preparing its 250 mg tablets of azithromycin;

3.          The specific ingredients and proportions of said ingredients which are used in tableting Apotex' azithromycin tablets; and

4.          Information of the Development Pharmaceutics including:

(a) description of any differences between Apotex' bulk material and the Canadian Reference Product; and

(b) description of any differences between Apotex' product and the Canadian Reference Product.

Applicants' Submission

[10]            The applicants submit that the type of information sought is available to Apotex but is not otherwise available to the applicants.

[11]            The applicants submit that the Food and Drug Regulations, C.R.C., c. 870, require a manufacturer to have samples available to be provided to the Minister when requested, and that these samples be kept for inspection purposes.

[12]            The applicants submit that the first person must satisfy the Court on a balance of probabilities that disclosure should be ordered. The applicants submit that the following is applicable from the June 19, 2000 decision in Novartis AG et al. v. Abbott Laboratories Ltd. et al. 7 C.P.R. (4th) 264 (F.C.A.) per Rothstein J.A.:

¶ _17 In SmithKline Beecham Pharma Inc. v. Apotex Inc. (1999), 3 C.P.R. (4th) 22 (F.C.T.D.), McGillis J. had occasion to order disclosure under subsection 6(7). At paragraph 8, she stated:

In my opinion, SmithKline has established on a balance of probabilities that disclosure of the full process for the manufacture of Apotex' paroxetine hydrochloride is required to provide evidentiary foundation for assessing the allegation of non-infringement in relation, at least, to the product by process claim in claim 5 of the '023 patent. I also note that the evidence of Dr. Fallis that it would be "important", in determining the question of infringement, to assess the further processing done by Apotex after the recrystallization step revealed in the disclosed materials was not undermined in cross-examination. [Emphasis added.]   

In SmithKline, McGillis J. found that SmithKline had established on a balance of probabilities that disclosure was required. She also had regard to the criteria of importance. I think whether disclosure is required and is important are appropriate considerations for the exercise of discretion under subsection 6(7).

[13]            In the April 2, 2001 decision of Glaxo Group Ltd. v. Canada (Minister of National Health and Welfare) 11 C.P.R. (4th) 417, Richard C.J. refers to the Novartis, supra decision and the production of relevant portions of the ANDS at 424 as follows:

¶ 37 However, Glaxo had other means available with which to compel the necessary information. Subsection 6(7) of the Regulations provides a mechanism by which a first person such as Glaxo may compel production of any relevant portions of an ANDS. It reads as follows: . . .

¶ 38 This Court has recently held that an application for production pursuant to s-s. 6(7) does not bear a heavy burden with respect to obtaining production: Novartis Pharmaceuticals Canada Inc. v. Abbott Laboratories, Ltd., [2000] F.C.J. No. 941 (QL) (F.C.A.) [reported 7 C.P.R. (4th) 264].

¶ 39 It was at all times open to Glaxo to pursue this remedy and to secure access to the information sought. Glaxo simply failed to do so, and now seeks to avoid the consequences of this failure. In circumstances where Glaxo had a clear opportunity to obtain this information and failed to do so for no apparent reason, it cannot be said that there is any burden or obligation whatsoever on Apotex to introduce evidence in support of an issue raised by Glaxo.

[14]            The applicants submit that the Court may consider whether there has been an adequate disclosure of the facts to allow the first person to effectively present its case. The applicant submits that in this case, Apotex has not provided sufficient information about its formulation to allow the applicants to challenge the NOA.

[15]            The applicants submit that if samples from Apotex show the presence of some of the dihydrate, then the Apotex allegation of non-infringement is clearly not justified.

[16]            The applicants submit that the formation of the dihyrdate when the monohydrate is prepared using the teachings of the ‘398 patent, or by conversion, make it not clear that Apotex' bulk and tablets will not contain some of the dihydrate, contrary to the NOA.

[17]            The applicants cite the January 4, 2001 decision of Noël J.A. in SmithKline Beecham Pharma Inc. et al. v. Apotex Inc. et al. 10 C.P.R. (4th) 338 at page 347:

¶ 30 Even if the notices of allegation were not deficient, SmithKline maintains that the allegation remains unjustified when regard is had to the common law presumption which operates in its favour. According to SmithKline, the motions judge failed to give effect to this presumption.

¶ 31 In support of this contention, SmithKline relies on the fact that the only information provided to it by Apotex pertained to the method and process for making the anhydrate; no information was provided as to how the anhydrate would be tableted and what steps would be taken to avoid conversion. As this information was within the exclusive knowledge of Apotex, SmithKline argues that the motions judge was bound to presume that Apotex' tableting process would result in the anhydrate converting into the hemihydrate.

¶ 32 SmithKline has established only one of the two conditions precedent to the application of the common law presumption:

. . . before giving effect to the presumption the court would have to be satisfied that the information was not in the possession of the respondents, and was [page348] peculiarly within the knowledge of the appellant. It would also be necessary for the Respondents to show that the required information was not adduced in evidence by the Appellant and that the Respondents did not have available other means of accessing it (Nu-Pharm, supra, at 19).

¶ 33 The record on appeal does not show that SmithKline made any attempt to obtain this information or to compel its production. Yet the case law, as it stood at the relevant time, suggests that the information might well have been accessible to SmithKline upon the appropriate motion being brought (SmithKline Beecham Pharma Inc. v. Apotex Inc. (1999), 3 C.P.R. (4th) 22 (F.C.T.D.) at 27). Further, if asked, Apotex might have supplied it voluntarily. It follows that the common law presumption cannot come to the aid of SmithKline in this instance.

The applicants submit that the SmithKline, supra proceeding was commenced before subsection 6(7) was introduced and so even under the more restrictive test that existed prior to subsection 6(7), the Court of Appeal envisioned that samples could have been compellable by the Court.

[18]            The applicants submit that if Apotex had provided the information and samples when requested, the applicants would have had about 75 days within which to prepare and file its evidence. The applicants submit that a minimum of 60 days to file further evidence should be granted to allow the applicants to undertake experimentation once the material is disclosed.

Respondent Apotex's Submissions

[19]            Apotex submits that assertions of fact as to non-infringement contained in a NOA are presumed to be true.

[20]            Apotex submits that in order for the Court to exercise its discretion, it must first be established as a condition precedent that the information sought is relevant to the issues in the proceeding. Once this condition is satisfied, Apotex submits that the exercise of the Court's discretion should be guided by whether disclosure is "required and important" (Novartis, supra).

[21]            Apotex submits that the only relevant claim of the ‘876 patent, claim one, is a claim to the dihydrate product and there is no relevant claim in connection with the process to manufacture such a product. Apotex submits that accordingly, any information in respect of how Apotex manufactures its azithromycin tablets is not relevant.

[22]            Apotex submits that the patent defines the dihydrate by referring to it having a 4.6% water content. Apotex submits that Apotex' azithromycin product cannot have a water content of less than 2% and greater than 3% and therefore will clearly not be within the scope of the ‘876 patent.

[23]            Apotex points to the November, 1998 decision of Rothstein J. (as he then was) in Hoffman-La Roche Ltd. et al. v. Minister of National Health and Welfare et al. [1998] 85 C.P.R. (3d) 50 where he wrote at pages 54 to 55:

Subsection 6(7) will apply to prohibition proceedings where the court considers it necessary to see a portion of a submission for a notice of compliance in order to make a determination under the Regulations. That will not be in every proceeding and it is certainly not necessary in this proceeding. I think the dicta of Stone J.A. is conclusive with respect to the matter at issue here. Certainly, if Pro Doc's ticlopidine hydrochloride reaches the market, the applicants will have an opportunity to analyze it. If it were shown to contain one of the acids listed in claim 1, contrary to Pro Doc's notice of allegation, the consequences for Pro Doc could be very serious indeed. In the circumstances here, as in the prior cases involving the ‘170 patent, I accept that Pro Doc intends its notice of allegation to be accurate.

[24]            Apotex further points to the March, 1999 decision of Sharlow J. (as she then was) in Hoffman-La Roche Ltd. et al. v. Minister of National Health and Welfare et al. [1999] 87 C.P.R. (3d) at 251, where she wrote at page 260:

Hoffman argues that it would be unfair to halt its prohibition application at this stage because it will be deprived of its right to seek disclosure of the new drug submission as permitted by section 6(7) of the Regulations, and thus its right to test the truth of the facts stated in the notice of allegation. Hoffmann has made no application under that provision since receiving the notice of allegation in November of 1998, over three months before the hearing of this application.

Apotex submits that the applicants did not properly follow the teaching of the ‘398 application in the preparation of their monohydrate sample. Apotex submits that the results of such a failure are entirely irrelevant to Apotex' assertion of non-infringement.

[25]            Issues

1.          Should an order issue granting the requested material be provided by Apotex to the applicants?

2.          Should the applicants receive an extension of time to file further evidence?

Relevant Statutory Provisions and Regulations

[26]            Subsections 6(7) and (8) of the NOC Regulations state:

Analysis and Decision

[27]            Issue 1

Should an order issue granting the requested material be provided by Apotex to the applicants?

Production of Samples

The respondents seek to rely on the 1996 decision of Hoffman La-Roche Ltd. v. Canada (1996), 67 C.P.R. (3d) 484 (F.C.T.D.) for the proposition that production of samples is inappropriate under the NOC Regulations. However, the provision under which the applicants seek the production of samples, subsection 6(7) of the NOC Regulations, came into force in 1998. Accordingly, the cited 1996 decision does not address subsection 6(7) of the NOC Regulations.

[28]            Whether samples are compellable under subsection 6(7), in my view, depends upon whether the samples were provided to the Minister as part of the submission for a notice of compliance. Apotex submits that the applicants have not shown that Apotex provided samples to the Minister and that accordingly, this remedy should not be available. Whether or not samples were provided by Apotex to the Minster is information exclusively known to Apotex and the Minister, and is not readily available to the applicants. In my reading of subsection 6(7), samples can be compellable only if they have been provided to the Minister. Subsection 6(7)(b) provides authority for an order that the Minister verify that the portions produced corresponds fully to the information in the submission.

[29]            I am prepared to proceed on the assumption that samples were provided to the Minister and are compellable under subsection 6(7). In the event that they were not provided to the Minister, and the Minister can verify that fact, then Apotex will not be required to produce samples for the applicants. Any order will reflect this.

[30]            Production Should Be Granted

The relevance of the requested material is a condition precedent to the exercise of discretion under subsection 6(7). Following the analysis of Rothstein J.A. in Novartis, supra, appropriate considerations for the exercise of discretion under subsection 6(7) include whether disclosure is required and is important.

[31]            The evidence introduced by the applicants has clearly raised the possibility that the Apotex tablets, claiming to contain only the monohydrate, contain some of the dihydrate. Paragraphs 15 and 16 of the affidavit of George Quallich reads as follows:

Subsequently, I understand that in response to a request by the Applicants' [sic], Apotex provided some further information in a letter dated December 4, 2001 and enclosed with the letter two sheets entitled "Specification and Certificate of Analysis-Raw Material". Therein, it is indicated that the form of Apotex' product is azithromycin isopropanolate monohydrate. Azithromycin isopropanolate monohydrate is another name for azithromycin monnohydrate isopropanol clathrate disclosed in the ‘398 application.

Based on the information contained on the two sheets, it is impossible for me to determine whether the product contains any dihydrate. Moreover, considering the material Pfizer made up following the directions in the ‘398 application and the fact that the clathrate converts overtime to the dihydrate, I believe, that Apotex' proposed commercial material will likely contain some dihydrate.

If this is proven, the applicants are correct in asserting that the ‘876 would be infringed by the Apotex product.

[32]            Production of requested material is clearly relevant to the issues in this proceeding as it will enable the applicants to examine whether the tablets do include the dihydrate and would infringe the ‘876 patent. The production of samples is required to enable the applicants to analyse the tablets so that this Court will have access to relevant information in determining whether the NOA is justified.

[33]            Apotex has argued that their tablets have a different water content than the dihydrate as claimed in the ‘876 patent. This remains an assertion that is untested by the applicants. Even if the tablets have a different water content than tablets composed purely of dihydrate, production of the samples will enable the applicants to determine whether the Apotex tablets contain any dihydrate. In my view, this information is important to the outcome of this proceeding.

[34]            In the exercise of my discretion, on the evidence before me, I am satisfied on the balance of probabilities that the production of the requested information and samples are necessary to provide the evidentiary foundation for this Court to assess the allegations of non-infringement.

[35]            Issue 2

Should the applicants receive an extension of time to file further evidence?

The applicants should be provided with an opportunity to examine the material produced by Apotex and be able to file further evidence. Accordingly, I am prepared to grant the applicants an extension of the time to file evidence in this proceeding for a period of 60 days following the production of material by Apotex.

[36]            The motion of the applicant is hereby granted.

[37]            Costs shall be costs in the cause.

ORDER

[38]            IT IS ORDERED that:

1.          Apotex shall provide the applicants with the portions of the ANDS that detail:

(a)         The process to make bulk azithromycin;

(b)         The tableting process for preparing its 250 mg tablets of azithromycin;

(c)         The specific ingredients and proportions of said ingredients which are used in tableting Apotex' azithromycin tablets; and

(d)         Information of the Development Pharmaceutics including:

(i)          Description of any differences between Apotex' bulk material and the Canadian Reference Product; and

(ii)         Description of any differences between Apotex' product and the Canadian Reference Product.

2.          The production of samples is ordered as follows:

(a)         If Apotex provided samples of their azithromycin tablets to the Minister in their submissions for a notice of compliance, Apotex is required to produce for the applicants:

(i)          Randomly selected from each batch made to date using Apotex' formulation process, 100 azithromycin tablets; and,

(ii)         100 grams of bulk azithromycin used in manufacturing each batch made to date of Apotex' azithromycin tablets.

(b)         In the alternative, if Apotex did not provide any samples of azithromycin tablets in their submissions to the Minister for a notice of compliance, Apotex is required to disclose this information and will not be required to produce samples for the applicants.

3.          Subsection 6(8) of the NOC Regulations with respect to confidentiality shall apply to productions made pursuant to this order.

4.          All of the information and samples to be provided are to be provided subject to a protective order. The terms of the protective order and timing of the disclosure shall be agreed upon and settled by the parties no later than 10 days from the date of this order. Any dispute arising in that regard shall be determined on the basis of a further notice of motion.

5.          With respect to any portions of the ANDS produced by Apotex pursuant to paragraphs 1 and 2, the Minister of Health shall verify that such productions correspond fully to the information in the ANDS pending before the Minister.

6.          The time for the filing of the applicants' evidence is extended to 60 days following any production made pursuant to this order.

7.          Costs shall be costs in the cause.

                                                                                    "John A. O'Keefe"             

                                                                                                      J.F.C.C.                      

Ottawa, Ontario

May 3, 2002