in the high court of south africa (south eastern cape ... · in the high court of south africa...
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IN THE HIGH COURT OF SOUTH AFRICA
(SOUTH EASTERN CAPE LOCAL DIVISION) CASE NO: 1481/2007
In the matter between:
B BRAUN MEDICAL (PTY) LIMITED
APPLICANT
and
FRESENUS KABI SOUTH AFRICA (PTY) LTD RESPONDENT
JUDGMENT
DAMBUZA J:
1. In this matter, the applicant seeks an interim interdict, on an urgent basis,
restraining the respondent from distributing certain documents and from
otherwise spreading offending information about a medical product
marketed and sold by the applicant known as Venofundin which is
apparently similar medical product known as Voluven marketed and sold
by the respondent.
2. There is also an application, brought by the respondent, for leave to
supplement its answering affidavit.
3. The applicant, a wholly owned subsidiary of B Braun Melsungen AG, a
private German Company, and the respondent, a South African Company,
are competing pharmaceutical companies which operate within the
country and internationally. The medical products in question are a colloid
plasma volume substitute that is used during surgical operations and in
emergency units of hospitals and clinics. Venofundin is a potato based
product also known as hydroxyethl starch (HES) 130/0.42/6:1 whilst
Voluven is maize or waxycorn derivative alternatively known as HES
130/0.4/9:1. The respondent’s Voluven product has been used in South
Africa since 2002 and internationally since 1999. The applicant’s
Venofundin is relatively new, having been registered in South Africa on 2
March 2007 and launched at the end of March 2007.
4. The facts giving rise to this application are largely common cause. On 22
May 2007 representatives of both parties attended a seminar held at 1
Military Hospital in Pretoria. Various other competitors in the same market
2
as the parties also attended the seminar and presented their volume
replacement therapy products to senior members of the military. The
respondent’s national sales manager, Marlize Haarde made a
presentation in respect of the respondent’s Voluven and Armin Junkuhn,
a divisional manager in the employ of the applicant, made a
representation in respect of Venofundin. In the course of her presentation
Haarde referred to the applicant’s Venofundin, stating, amongst others,
that:
4.1 Doses of up to 33ml/kg of Venofundin are associated with hyperbilirubinaemia
(excessive concentration of bilirubin (a bile pigment) in the blood) ;
4.4 Venofundin is contra–indicated for liver failure in its European package insert
whereas in South Africa it is not;
4.2 The potato based HES product is registered for a dosage of 33ml/kg, with a
maximum daily dosage of 40ml/kg in acute cases and there is no data for
administration of higher doses thereof ; and
4.3 The potatoderived HES has a greater effect on (blood) coagulation than waxy
corn derived .
5. These statements appear in a 36 page document prepared by the
respondent titled “VOLUVEN Colloids Overview” (the respondent’s
pamphlet or Annexure “E” to the founding papers). This document was
distributed by Haarde at the seminar. In this document Volume
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Replacement Therapy is discussed and a comparison is drawn between
Voluven and Venofundin. In the comparison it is also stated that:
A the Amylopectin/Amylase content of the products is 95/5 for Voluven and
80/20 for Venofundin;
B Unlike with Voluven, there is no information available on the safety of
Venofundin use in paediatrics; and
C Unlike with Voluven there is no information available in respect of
Venofundin regarding tissue storage, renal function, toxicology and
compatibility with other drugs.
6. In the founding affidavit Junkuhn states that on 17 April 2007 he received
an enquiry from Carole Lawrence of the Life Healthcare Hospital
Groups in the country, requesting clarification on queries that she (Lewis)
had received concerning Venofundin. According to Lewis there were
insinuations that because Venofundin is registered as a hetastarch this
could have clinical consequences, particularly regarding coagulation; that
because Venofundin contains a fair amount of phosphates it could have
more extensive side effects than Voluven; that contrary to the only article
used in the applicant's detail aids, written by Lehman et al, a few
published studies showed that Voluven has a greater plasma clearance
than Venofundin; and that potatoderived HES has a greater effect on
coagulation than cornderived HES. Lewis also enquired whether the
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applicant had a safety data for use of Venofundin in paediatrics and
patients with compromised renal or hepatic function.
7. The applicant received further queries from Entabeni Hospital in Durban,
expressing concern about the amylopectin/amylase ratio for Venofundin
and Voluven being different; there being no data available for Venofundin
regarding tissue storage; Venofundin being contraindicated for liver
failure in the European package insert but not in the South African
package insert; Venofundin dosages of up to 33 ml/kg being associated
with hyperbilirubinaemia; unavailability of toxicological data for
Venofundin; and unavailability of information regarding compatibility of
Venofundin with other drugs.
8. The applicant contends that the only conclusion to be drawn from the
similarity between the queries raised by Lawrence and Entabeni
Hospital and the contents of the respondent’s pamphlet, Annexure “E” is
that the respondent’s representatives had been spreading injurious
falsehoods and unsubstantiated rumours concerning Venofundin. Such
conduct on the part of the respondent, so argues the applicant, constitutes
unlawful competition. The applicant’s case is that in Annexure “E”, the
respondent has made reference to articles written by medical experts on
the products, thus misleading the reader by giving an impression that the
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statements complained of are supported by medical evidence. Mr
Mundell submitted on behalf of the applicant that the respondent has
undertaken a deliberate extensive campaign of falsely maligning the
applicant’s Venofundin product by suggesting that the product is unsafe
and has negative side effects which render Venofundin a less safe and a
less acceptable alternative when compared to Voluven whilst on the other
hand, claiming unwarranted accolades for Voluven.
9. The respondent denies that the statements in question are false and that
its conduct constitutes unlawful competition. It contends that the
statements find support in the studies and articles referred to in Annexure
“E” and in the package inserts of the products.
10. Requirements for an interim interdict and unlawful competition
It is trite that ordinarily an applicant seeking an interim interdict must prove
a prima facie right, a wellgrounded apprehension of harm if the interim
interdict is not granted and the ultimate relief is ultimately granted, a
balance of convenience in favour of the granting of the relief sought and
absence of an alternative remedy. See Steel and Engineering Industries
Federation and Others v National Union of Metal Workers of South
6
Africa (2) 1993 (4) SA 196 (T) 199 G – 205 J; Setlogelo v Setlogelo
1914 AD 221; L F Boshoff Investments (Pty) Ltd v Cape Town
Municipality, Cape Town Municipality v L F Boshoff Investments
(Pty) Ltd 1969 2 SA 256 (C) 267.
11. In an action for damages founded on unlawful competition, a party alleging
injurious falsehood has to allege and prove that the other party has, by
word or conduct or both, made false representations; that it had known the
representations to be false; that the plaintiff had lost or would lose
customers; that the false representation had been the cause thereof; and
the defendant had intended to cause the plaintiff loss by the false
representation. Geary & Son (Pty) Ltd v Gove 1964 (1) SA 434 (A).
Fault, however, is not a requirement for an interdict directed at prevention
of unlawful competition. See Van Heerden and Neethling; Unlawful
Competition at 69; Schultz v Butt 1986 (3) SA 667 (A).
12. The applicant's case, as I understand it, is that the respondent's conduct
constitutes unlawful interference with its (respondent's) right to engage in
its trade and to market Venofundin. It contends that the respondent's
conduct of publishing and distributing injurious falsehood and misleading
customers about Venofundin constitutes unlawful competition.
7
13. That the applicant is entitled to the free exercise of its trade cannot be
disputed. According to the authors Van Heerden and Neethling (supra at
283):
"The direct infringment of the goodwill of a competitor's undertaking by the
publication of disparaging, untrue statements about his business, goods or
services, is undoubtedly unlawful. Such a direct attack on a rival is clearly in
conflict with the competition principle (and therefore contra bonos mores ):
there is no question of performance (merit) competition because the perpetrator
is deceiving the public as to the merit of his rival's performance"
See also Abakor Ltd v Crafcor Farming (Pty) Ltd t/a Riversdale
Feedlot 2001 (1) 973 (N).
However, this right to free exercise of trade is not without limitations.
There is a general acceptance that because of selfinterest, competitors
cannot evaluate their performances and products objectively and
impartially. Misleading images therefore become an almost inevitable
feature of comparative advertising even if only to a small extent. The
South African Courts, in line with English and American law, have held
that publication of true disparaging statement is lawful. In Post
Newspapers (Pty) Ltd v World Printing and Publishing Co Ltd 1970
(1) SA 454 (W) Nicholas J held at 456 FG that:
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" But where a trader does not limit himself to a comparison of his goods with
those manufactured by another trader and a mere statement that they are inferior
to his own, but makes some untrue statement of fact about his rival's goods for
example, states that they are rotten or contain deleterious ingredients an action
on the case will lie, on proof that such statement was published maliciously and
(save in cases falling within the provisions of the Defamation Act 1952, sec 3 (1)
that special damage has ensued.
'The general position in our law is: comparison yes; but disparagement no'
(per Hodson LJ; in Cellacite & British Uralite v Robertson, The Times, July 23rd,
1957 (C.A.)
There can be no doubt, on the authority of Fitchard's case, and subsequent
cases that such statements would be actionable in our law."
This principle has been criticised on the basis that where a true
disparaging statement is irrelevant to the competitive struggle concerned,
it should be wrongful. See Van Heerden and Neethling (supra) at 302. In
this case, however, the application is founded on falsity and misleading
nature of the statements. Further, I am satisfied that the statements under
consideration are relevant to the competitive struggle between the parties.
14. According to the respondent Annexure “E” was prepared in the context of
the parties’ mutual clients having requested the respondent to furnish
them with medical and scientific information regarding the differences
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between the two products i.e. the differences between potato based starch
and maize starch based HES. The request followed, so says the
respondent, the applicant having represented to customers that Voluven
and Venofundin are bioequivalents; that Venofundin is similar to and/or
better than or equivalent to or safer than Voluven; that Venofundin is the
worlds’ fastest, most efficient, fluid replacement system, is a new
technologically improved, chemically modified HES 130. The respondent
contends that the first group of statements carries with them the inference
that Venofundin is medically superior in a number of respects including
that it is safer and/or associated with less risk and/or improved results and
that the second group constitutes passing off and/or injurious falsehood on
the part of the applicant. The respondent contends that in preparing
Annexure “E” it sought to draw a distinction between the two products, to
enable its representatives to respond to queries from customers to whom
representations had been made on Venofundin. Needles to say the
respondent denies that the statements are misleading and/or constitute
injurious falsehood. The applicant, on the other hand, denies that it
attempted to market Venofundin as a bioequivalent of Voluven and
maintains that it could not have done so given the pharmaceutical
differences of the products; one being a potato starch and the other, a
maize starch based product. The applicant contends that the rest of the
statements attributed to it are nothing more than mere puffery.
10
15. Against this background I then proceed to consider whether the
statements in question constitute injurious falsehoods, were made without
basis and/ or are misleading insofar as they relate to the two products.
16. That doses of up to 33ml/kg of VENOFUNDIN are associated with
hyperbilirubinaemia
The applicant contends that this statement is false and that it was
intended to communicate that doses of up to 33ml/kg of Venofundin are
associated with hyperbilirubinaemia, which could indicate possible liver
dysfunction. According to the respondent the statement finds support in an
article written by medical experts Sander, Reinhart and MeierHellmann
in 2003. The respondent points that in Annexure “E” reference is made to
this and other articles written by experts in the medical field to safeguard
against possible misinterpretation of the statements. It is common cause
that the article by Sander et al which forms part of the record, is based on
a study comparing Venofundin and another potato based product, the 6%
HSE 200/0.5. In the article the authors state that:
“A novel potato starchbased HES solution (HES 130/0.4) was developed
by B Braun Melsungen AG…..
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This trial was designed as an approval study for B Braun Melsungen AG
and Serumwer Bernberg AG…..
Amount of colloidal infusions were adjusted individually up to the
recommended daily dosage of 33ml/kg bodyweight for pentastarches like
6% HES 130/0.4 and 6% HES 200/0.5 (10,17)…..
A total of 36 equally distributed adverse events (AE) with unlikely or
questionable relationship to the study drugs were documented (17AE in
the HES 200/0.5 group and 19 in the HES 130/0.4 group, respectively.
The most common AE was mild to moderate hyperbilirubinaemia at the
morning of the first postoperative day with questionable relationship to
study medication ….
In safety assessment, the most adverse event was mild to moderate
hyperbilirubinaemia. However this was seen in a few patients of both
study groups, with questionable relationship to study drugs.”
17. The applicant contends that the statement, in failing to reveal that the
experts concluded that the relationship between hyperbilirubinamea
observed in patients and the study drugs, is misleading and that in the
12
light of this inconclusive result the article cannot be valid foundation for the
conclusion drawn by the respondent. According to the applicant post
operative hyperbilirubinaemia may be introduced by impaired excretion of
bile, "possibly due to lowered intestinal perfusion and aggravated by an increased
bilirubin supply from fragmented erythrocytes or certain concomitant medication such as
antibiotics".
18. My understanding of this contention is that other factors, (other than the
study drugs), may cause postoperative hyperbilirubinaemia. The
applicant contends further that the statement compels the reader thereof
to draw the conclusion that the safety characteristics of Voluven exceed
those of Venofundin in that Voluven is not associated with
hyperbilirubinaemia whereas Venofundin is. From the evidence before me,
I am of the view that a reader of the statement who has background
knowledge of Voluven may indeed draw from the statement, the
conclusion put forth by the applicant. But that conclusion may, in my view,
be drawn from a mere reading the article. Further, I am not able to find
any basis on which to conclude that the statement is false. The applicant
does not demonstrate that Voluven is not associated with
hyperbilirubinaemia. It does not explain why the statement is false. It does
not dispute the assertion by the respondent that despite the numerous
tests done on Voluven, there has been no association between the
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product and hyperbilirubinaemia. Whilst it is true that the Sander article
does not conclude that Venofundin causes hyperbilirubinaemia, it is not
true that the article does not associate Venofundin or potato starch HSE
with hyperbilirubinaemia. Even if the Sander study is inconclusive on the
association between Venofundin and hyperbilirubinaemia, that does not
make the statement false. Neither does the fact that other factors may
cause hyperbilirubinaemia.
19. That in the European package insert Venofundin is contra – indicated
for liver failure whereas in the South African version it is not.
The applicant contends that the statement is false and is intended to warn
the applicant’s customers that Venofundin can cause liver damage or
impairment of liver function. The applicant argues that the South African
package insert, under the heading "warnings", does warn of a contra
indication for liver or hepatic dysfunction. It is not in dispute that a
contraindication in a package insert of a medical product is the portion
thereof which informs the reader that a particular medicine should not be
used in patients or persons with a particular medical and/or physical
condition as stipulated in the insert.
14
In the South African version of Venofundin package insert, the following
appears:
"CONTRA INDICATIONS
•Hypersensitivity to hydroxyethyl starch or any of the other ingredients.
•Intracranial bleeding.
•Renal failure with oliguria or anuria.
•Dialysis treatment.
•Sever hypernatremia or severe hyperchloremia.
•Fluid overload (hyperhydration) including pulmonary oedema."
20. The contraindications in the German European Venofundin package
insert have been translated by the respondent as follows:
"Gegenanzeigen [Contraindications]
.....Schwere leberfunktionseinschrankung [Severely impaired hepatic [liver]
function [i.e. liver failure]]..."
21. In the English version of the European Venofundin package insert the
contraindications appear as:
"Contraindications
Hyperhydration states including pulmonary edema.
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Renal failure with oliguria or anuria
Intracranial bleeding
Severe hypernatremia or severe hyperchloremia
Hypersensitivity to hydrxyethyl starch or to any of the excipients.
Severely impaired hepatic function.
Congestive cardiac failure"
22. By all accounts it appears to be factually correct that contrary to the
European version, the South African Venofundin package insert contains
no contraindication for severely impaired hepatic function. The warning
issued in the South African package insert of Venofundin is that: "[p]articular
caution should be exercised in patients with hepatic insufficiency, pulmonary oedema and
in those with blood coagulation disorders". This warning, in my view simply
means that particular care should be taken when administering the
product to patients suffering from the stated conditions. It falls short of
advising that the product should not be administered to patients suffering
from such stated conditions. I am therefore satisfied that the statement is
neither misleading nor false.
23. That the potatoderived HES has a greater effect on (blood)
coagulation than the waxycorn derived HES.
It is common cause that this statement was drawn by the respondent from
an article written by M Jamnicki and others titled "The effect of potato
16
starch derived and corn starch derived hydroxyethyl starch on in
vitro blood coagulation". At the beginning of the article the authors say:
“The present study was designed to investigate the effects on in
vitro blood coagulation of a newly developed potato starch derived hydroxyethyl
starch (HES) and to compare those effects with those of the traditional corn
starch derived HES, as assessed by thrombelastography (TEG).”
24. The applicant contends that the respondent was not entitled to extrapolate
the Jamnicki study to Venofundin and Voluven as the study was not done
on these product. It is so that the Jamnicki study did not compare Voluven
and Venofunden. It compared a potatobased HES (INFUKOLL HES 6%)
and a maizebased HES (HAES steril 6%) and the authors concluded
that “potato starch derived hydroxyethyl starch compromises in vitro blood
coagulation more that corn starch derived hydroxyethyl starch.” The
applicant's case in this regard, as I understand it, is that data acquired in
clinical studies on a potato and maize based HES cannot be utilised to
infer similar properties in Venofundin and Voluven. There is, however, no
explanation why such an inference cannot be made either generally or in
this particular case. Whilst the Jamnicki study does not specifically refer to
Venofundin and Voluven, the products in question are derived from potato
starch and maize starch. I find no basis to conclude that the respondent's
17
reliance on the study is not justified as submitted by Mr Mundell on behalf
of the applicant.
25. The applicant contends that there is essentially no distinction between
Venofundin and Voluven insofar as they are associated with blood
coagulation. In this regard the applicant relies on an opinion of Dr Gernot
Willy Konrad Marx, an international medical expert whose opinion is that
the fact that package inserts for both Venofundin and Voluven indicate
that care must be taken when administering the products to patients with
severe liver disease or severe bleeding disorders negates the distinction
which the respondent seeks to draw between the two products. According
to Dr Marx a recent trial comparing Venofundin and Voluven showed a
general bioequivalence. He states that there is no evidence that doses of
up to 33ml/kg of Venofundin have been associated with
hyperbilirubinaemia and maintains that the study on which the respondent
relies in associating Venofundin with liver impairment and/or
hyperbilirubinaemia does not justify the conclusion drawn by the
respondent. He points out that in the Sander study the authors measured
bilirubin which had not been investigated in previous trials on volume
replacement therapy. My view is that the fact that levels of bilirubin were
not measured in previous studies has no effect on the results of a study
wherein bilirubin was measured. Nor does that fact demonstrate that there
18
is no association between Venofundin and hyperbilirubinaemia. It also
does not detract from the uncontested assertion that no studies have
shown an association between hyperbilirubinaemia and Voluven.
26. Further, as Mr Rowan submitted on behalf of the respondent, Dr Marx's
opinion that the two products are bioequivalent and/or their end product is
identical, is rendered doubtfully an article coauthored by the same Dr
Max, G Lehman and H Forster, in which it is concluded that the two
products must be considered as not being bioequivalent. Another expert,
Professor Guy Richards, in a written opinion states that:
"The Lehman study (of which Prof Gernot Marx is a coauthor) and the
Sommermeyer report (attached) indicate that Voluven and Veonofundin are not
bioequivalent. In fact the raw materials utilized are entirely different waxy maize
for Voluven and potato for Venofundin). As a consequence these products have
a significant potential effect on their pharmacokinetic profiles".
27. Drs Klaus Sommermeyer, Franz Cech and Richada Scchossow also
point out that postoperative hyperbilirubinaemia is a side effect not known
in waxy maize starch derived HES. They conclude that "waxy maize and
potato starch based hdroxyethyl starch plasma volume expanders differ in their chemical
fine structure. Their pharmacological and clinical equivalence remains to be proven with
further studies". Dr Sommermeyer's opinion is that in the light of the physio
19
chemical differences between the two products, the claimed similarity of
potato starch based products to waxy corn starch based products is not
justified because theoretical arguments and published data indicate a
higher inference on coagulation of the potato starch based products.
28. That Venofundin is registered for a dosage of 33ml/kg bodyweight;
with the maximum dosage of 40ml/kg for one day in acute cases (and
there is no data for higher doses).
In contending that this statement is false the applicant refers to the
European package insert of Venofundin and an article written by Dr Marx.
The relevant portion on the South African package insert for Venofundin
reads:
" ...The maximum daily dosage is 33/ml/kg body weight per day...
In cases of acute and severe bleeding a higher dose may be given for 1 day if
indicated after the risk/benefit analysis. However, dosage of more than 40ml/kg
bodyweight per day should not be exceeded". (emphasis supplied)
In the European package insert the following appears:
"The maximum infusion rate depends on the clinical situation. Patients in acute
shock may be administered up to 20ml per kg of body weight per hour
(equivalent to 0,33mlkg/min or 1.2g of hdroxyethyl starch per kg of bodyweight
20
per hour). In life threatening situations 500ml may be administered by manual
pressure infusion. Also see "Method of administration and duration of therapy.
Maximum daily dose:
Up to 50ml of Venofundin per kg of body weight (equivalent to 3.0g of
hydroxyethyl starch per kg of bodyweight). This is equivalent to 3,500ml of
Venofundin for a 70 kg patient."
Dr Marx, in his written opinion to the applicant, states that:
"In the European SPC the maximum infusion rate of Venofundin is 50ml/kg body
weight over 24 hours similar to the SPC of Voluven.In the South African SPC of
Venofundin it is stated that the maximum infusion rate depends on the clinical
situation. There is no scientific reason that the infusion rate of one drug should
be different between Europe and South Africa".
The opinion is, however, silent on the instruction in the South African
insert that dosage of more that 40ml/kg per day of Venofundin should not
be administered. My view is that in the light of this warning in the South
African leaflet, the fact that the European package insert provides for
administration of higher dosage of the product is irrelevant to a South
African reader of the leaflet or user of the product. In this light therefore,
the statement cannot, in my view, mislead or constitute injurious falsehood
or unlawful competition.
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29. To further disprove the distinction drawn by the respondent between the
two products, the applicant compares the "almost identical" package
inserts thereof. These include identical contraindications for both products;
the same maximum infusion rate for both products being 33ml/kg
bodyweight; both products being registered for similar side effects,
precautions, safety and efficacy in relation to children and use during
pregnancy and lactation. The applicant contends that the package inserts
reveal minimal meaningful distinction between the products and that the
statements are not justified in the light thereof. In my view the comparison
of the package leaflets does not prove the falsity of the statement or that
the statements are misleading. In any event, as the respondent contends,
the package insert used by the applicant in respect of Voluven is outdated,
having been used prior to 2004. The scope of Voluven has been widened
with the registration of the 2004 and 2007 package inserts for the product;
for example the 2004 package insert states that there has been limited
use of Voluven in children.
30. I am not persuaded that the statements made by the respondent are
misleading or constitute injurious falsehood and/or find no basis in the
articles cited by the respondent in Annexure “E”. Even if the criticism by
the applicant that the statements are not supported by the articles cited in
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Annexure “E” is well founded, it does not follow that the statements are
false. “It is an error to say that false premises must logically lead to propositions which
are false: it is plain that a good cause may have bad reasons offered on its behalf”.
Post Newspapers (supra) at 459 H. It is not the applicant’s case that
Venofundin is distinguishable from other potato based products and that
properties observed in other potato based products should therefore not
be attributed to Venofundin. On the other hand expert evidence suggests
that the results of studies done on potato derived starches are of
relevance to potato based products generally.
It is my view in the circumstances that the applicant has not made out a
case for the relief it seeks.
31. Application to file a supplementary answering affidavit.
The respondent wishes to supplement its answering affidavit for three
reasons. Firstly it contends that it needs to respond to certain issues
raised for the first time in the applicant’s replying affidavit. It further seeks
to place before the court certain information that it was previously unaware
of. It also seeks to place before court certain expert evidence that it could
not file with the answering affidavit because of time constraints.
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32. New Matter
In the replying affidavit the applicant attached a document (annexure R 5)
titled;
"VOLUVEN vs Venofundin
Internal use only Arguments for the market"
The document is yet another comparison between the two products.
Amongst others, the following appears on the document:
VOLUVEN VENOFUNDENStudies available #1 in a SAFETY
> 60 VOLUVEN studies proving safety
3 studies (2 published)use Voluven studies for argument
Dose limit 45ml/kg registrationNeff 2003 proved 70ml/kg/day for up to 28 days to be safe with no effect on renal function or coagulation
33ml/kg registration Venofundin SmPC says you can give maximum 40ml/kg for ONE day in acute cases
Blood typing before infusion
No SmPC No influence on blood groupserology Voluven scientific info
Yes according in European SmPC but no according to SA SmPC???
Infusion speed No limitations SmPC 20ml/kg/hour in European SmPC but not included in SA SmPC???
Liver failure Not contraindicated Contraindicated in European SmPC but no in SA SmPC???Sander 2003 Venofundin @ 33ml/kg associated with hyperbilirubinaemina
Coagulation Jamnicki 1998 compared HES 200/0.5 maize vs potato starch and showed potato starch to have greater effect on coagulation than maize starch
33. It is common cause that despite the document being an internal document
intended for use by the respondent's representatives, copies thereof were
24
handed to medical staff at hospitals in Vereeniging and at the West Coast
Life Hospital in the Western Cape. In the answering affidavit the applicant
contends that this document was a further attempt by the respondent to
persuade the staff at these hospitals that Venofundin has a greater effect
on coagulation than Voluven.
34. A fundamental consideration in an application for filing of further affidavits
is that a matter should be adjudicated upon all facts relevant to the issues
in dispute. South Peninsula Municipality v Evans 2001 (1) SA 271 (C)
at 283 AH. I am of the view that the contents of Annexure "R 5" are in
essence a repetition of allegations already made by the parties in the first
two sets of affidavits. They do not constitute new matter. The respondent,
in my view, answered to these allegations in the main answering affidavit.
That certain minor allegations were not included in the applicant's
founding papers (for example, the allegation in annexure R5 that there
are in excess of 60 studies proving safety of Voluven whereas there are
only three in respect of Venofundin) does not take the matter any further.
35. The respondent further takes issue with allegations made in paragraphs
40 to 45 of the replying affidavit. In these paragraphs the applicant refers
to the respondent’s distribution of the Jamnicki article to attendees of an
anaesthetic refresher course held at Groote Schuur Hospital from 2 to 5
25
August 2007. The applicant contends, in the replying affidavit, that the
article was distributed by the respondent with the intention to persuade the
persons to whom it was given, that Venofundin compromises in vitro blood
circulation more than corn starch HES such as Voluven. In paragraph 44
of the replying affidavit Junkhun refers to an incident in which a
representative of the respondent, Shelley, presented a copy of the
Jamnicki article to a specialist at St Augustine Hospital in Durban and
wrote on the article, in her handwriting, that the potato starch HES being
referred to in the article is Venofundin and the corn starch HES referred to
is Voluven. I am, again, of the view that these allegations are a repetition
of what is already contained in the parties' first two sets of affidavits. I can
only conclude that the applicant's intention, in citing these incidents, was
to demonstrate that the applicant persists with the offending conduct. In
view of the respondent’s denial of any wrongdoing, such persistence was
to be expected. In any event the incidents referred to in paragraphs 40 to
45 of the replying affidavit are, strictly speaking, not relevant to this
application and should be properly struck off from the record.
36. Facts that the respondent recently became aware of.
The information referred to by the respondent is a written comparative
analysis between Venofundin and Voluven prepared by the applicant. In
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this document the applicant states, amongst others, that both products are
produced to contain 100% of Amylopectin in the finished product and that
all Amylose is removed. The comparative analysis further states that corn
starch contains Sulphur and potato starch contains Phosphate, the
content of which, in both products, is very small and clinically irrelevant. I
can only conclude that all this is intended to disprove the distinction drawn
by the respondent between the two products. The respondent contends
that the truth is that the degree of esterification (modification) of
Phosphate in the potato starch HES derived product is higher in
comparison to the waxy maize starch derived product. Lastly the
respondent contends that contrary to the Lehman and Marx study, which
shows “advantages for Venofundin” in respect of plasma clearance, three
other studies conclude that Voluven has a faster clearance rate than that
reported in the Lehman study.
Once more, my view is that the applicant’s comparison adds nothing new
to the case made by the applicant in the founding papers. The respondent
may have only become aware of this document subsequent to the filing of
the answering affidavit. But the contents of the document are neither the
basis of the application nor the respondent's reason for preparing
Annexure “E”. It is therefore irrelevant to this application.
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37. The evidence of Drs Gopalan and Joubert
This evidence is contained in reports prepared by the two experts in
respect of certain aspects of the Sander study. The reports were
prepared on the respondent’s instruction but were not completed in time
for filing together with the answering affidavit. The respondent refers to
portions of the expert reports which refute the claims that the association
between Venofundin and Voluven finds no support in the Sander study.
Dr Gopalan remarks that:
“Hyperbilirubinemia is indeed an indication if impairment of liver function. The study
in question does indeed describe hyperbilirubinemia in patients included in the
study…..While this study does not prove causation with respect to the study
medication (Venofundin), it does potentially show an association. From a clinician’s
perspective, this would have to be born in mind with respect to drug administration
until further evidence either proves or refutes this association. Note the comparator
drug in this study was not Voluven (Venofundin) but a 200/0.5 potato derived starch.
From a scientific perspective, this raises the question as to whether
hyperbilirubinemia is associated specifically with potato derived solutions”.
Regarding contraindications for liver failure Dr Joubert states that:
“There is a clear distinction between a contraindication with respect to
administration and a warning with respect to administration. A contraindication
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would mandate non administration of the drug whereas a warning would be
seen as a strong cautionary advice with respect to administration of the drug.
It is very surprising that the European package insert for Venofundin carries a
contraindication for administration in severe, hepatic dysfunction, while the South
African version does’nt. From a clinician’s perspective this is of grave concern.”
38. It would appear that the assertions made by the Drs Gopalan and
Joubert in these paragraphs are the main motivation for seeking
admission of their affidavits and reports. But the respondent filed, together
with its main affidavits, reports and opinions by no less than four other
experts, including Drs Sommermeyer and Richards, who also warned
that the presence of postoperative hyperbilirubinaemia in patients on
whom Venofundin had been administered requires further investigation.
Further, the respondent, in the answering affidavit, explains conclusively
the difference between a "contraindication" and a "warning" in the
package insert of a medical product.
39. Having considered these aspects I am satisfied that the respondent
stands to suffer no prejudice if the filing of a supplementary
answering affidavit is not permitted. Further, in view of the irrelevant
allegations made in the applicant's replying affidavit, to which the
respondent sought to respond in the supplementary answering affidavit, I
am of the view that the appropriate costs order would for each party to pay
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its own costs in respect of the application for leave to file a supplementary
answering affidavit.
The following order shall therefore issue:
1. The interim relief sought is refused with costs;
2. The application for leave to file a supplementary answering affidavit is
dismissed with no order as to costs.
_________________________
N DAMBUZA
JUDGE OF THE HIGH COURT
Applicant’s Counsel: Adv Mundell
Applicant’s Attorneys: Greyvensteins Nortier
St George’s House
104 Park Drive
PORT ELIZABETH
30
Respondents’ Counsel: Adv Rowan
Respondent’s Attorneys: PagdensStultings
18 Castle Hill
Central
PORT ELIZABETH
Heard on: 1 November 2007
Delivered on: 15 April 2008
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