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[2015] ZAGPPHC 319
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Allergan Pharmaceuticals (Pty) Ltd v Medicines Control Council and Others (992/2015) [2015] ZAGPPHC 319; [2015] 3 All SA 173 (GP) (5 May 2015)
IN
THE GAUTENG DIVISION OF THE HIGH COURT, PRETORIA
(REPUBLIC
OF SOUTH AFRICA)
CASE
NO: 992/2015
DATE:
5 MAY 2015
In
the matter between:
ALLERGAN
PHARMACEUTICALS (PTY)
LTD
..............................................................
Applicant
And
MEDICINES
CONTROL
COUNCIL
........................................................................
First
Respondent
DIRECTOR-GENERAL
OF THE NATIONAL
DEPARTMENT
OF
HEALTH
.................................................................................
Second
Respondent
MINISTER
OF
HEALTH
...........................................................................................
Third
Respondent
JUDGMENT
JANSEN
J
[1]
This matter came before me on a semi-urgent basis. It was set
down earlier for 17 February 2015, but was not heard due
to its
voluminous nature and the intricacy thereof. The matter was
postponed to 20 March 2015.
[2]
At the hearing of the matter, counsel for the respondents sought to
file, on the day of the hearing, a fourth set of affidavits
(undeposed) by their expert, Professor Walubo (a clinical
pharmacologist who has a MBChB, a Masters (M.Phil) in Basic
Pharmacology,
a Doctor of Medicine (M.D.) in Clinical Pharmacology,
two-year post-doctoral training in Clinical Pharmacology and a
Masters in
Business Administration (MBA)). In the application
for the late filing of the affidavit (also not deposed to) it was
stated
that the applicant’s replying affidavit contained new
allegations and that the respondents were forced to approach him (on
an unknown date) to provide a detailed response to the applicant’s
replying affidavit. It was further stated that due
to prior
commitments (of which no details are provided) he was unable to
provide a detailed response to the applicants’ replying
affidavit timeously.
[3]
In any event, in the court’s opinion, the replying affidavit
does not contain new evidence. The mere fact that brief
confirmatory affidavits have been appended to the replying affidavit
cannot change the facts (and opinions based thereon) in the
replying
affidavit into “new evidence”.
[4]
That this “affidavit” for condonation of the filing of a
fourth affidavit is woefully inadequate, is obvious.
As a
result, it was disallowed. The e-mail accompanying the said
“application” and the fourth affidavit were
e-mailed to
the court and the applicant on 19 March 2015 at 5:46pm and contained
the following sentence: “
Be informed that the signed and
commissioned affidavits shall be served on you tomorrow morning
.”
Nature
of the application
[5]
The applicant seeks declaratory relief to the effect that the
applicant’s products are medical devices in terms of the
Medicines and Related Substances Act 101 of 1965 (“
the
Medicines Act
”).
[6]
The applicant’s products are called the Optive range of
products and have been sold in the Republic since 2007.
The
applicant contends that its range of products constitutes medical
devices and not medicines. This is the first issue
to be
decided in this application. On a previous occasion, the
applicant’s products were seized by Port Health (by
the
Director-General of the National Department of Health (“
DG
”)
and more recently another three shipments during September and
November 2014. The reason for the detention of the
shipments
was that they were allegedly medicines and had been called-up for
registration as such.
[7]
In the matter of
Gelderma Laboratories South Africa (Pty) Ltd v
Medicines Control Council and Others
(54281/2013) [2014]
ZAGPPHC 360 (12 June 2014)
heard by Ismail J in this division, it
was held that pending the promulgation of medical device regulations,
medical devices do
not fall to be regulated by the Medicines Control
Council (“
the MCC
”)
Is
the Optive range of products medicines or medical devices?
[8]
The first issue to be determined is whether the Optive products
constitute medicines or medical devices.
[9]
Medicines are defined in section 1 of the Medicines Act as
meaning:-
“
any
substance or mixture of substances used or purporting to be suitable
for use or manufactured or sold for use in-
(a)
the diagnosis, treatment, mitigation, modification or
prevention of disease, abnormal physical or mental state or the
symptoms thereof
in man; or
(b)
restoring, correcting or modifying any somatic or
psychic or organic function in man, and includes any veterinary
medicine
”
[10]
The definition of a medical device in the Medicines Act, in terms of
section 1(c) of Act 94 of 1991, is as follows: —
“…
any
instrument, appliance, material, machine, apparatus, implant or
diagnostic reagent –
(a)
used or purporting to be suitable for use or
manufactured or sold for use in –
(i)
the diagnosis, treatment, mitigation, modification,
monitoring or prevention of disease, abnormal physical or mental
states or the
symptoms thereof; or
(ii)
restoring, correcting or modifying any somatic or
psychic or organic function; or
(iii)
the diagnosis or prevention of pregnancy and which does
not achieve its purpose through chemical, pharmacological,
immunological
or metabolic means in or on the human body but which
may be assisted in its function by such means; or
(b) declared
by the Minister by notice in the Gazette to be a medical device and
includes any part or an accessory of a medical
device;
”
[11]
It should be noted that the Optive range of products are Ophthalmic
Lubricants/Dry Eye comfort solutions.
[12]
The MCC justified its attack on the Optive range of products as
allegedly in the interests of public safety, notwithstanding
the fact
that the applicant demonstrated in its papers that similar products
of the competitors are to be found on the shelves
of pharmacies and
are sold on a daily basis to members of the public.
[13]
Furthermore, the applicant refers to various countries across the
world where the Optive range of products has been classified,
documented and registered as medical devices and not medicines,
namely:—
“
The
Australian Department of Health and Therapeutic Goods Administration
(‘TGA’) in Australia; the Medicines and Healthcare
Products Regulatory Agency (‘MHRA’) in the United
Kingdom, which ensures and administers compliance with medical device
legislation in England, Northern Ireland, Scotland and Wales; the
Food and Drug Administration (‘FDA’) in the United
States
of America where the Optive range of products trade under the name of
Refresh Optive and Refresh Optive Advanced.
”
[14]
The definition of a medical device which approximates the South
African definition the closest is the Australian definition
which
reads as follows: —
“
A
medical device is:
a.
any instrument, apparatus, appliance, material or other article
(whether used alone or in combination, and including the software
necessary for its proper application) intended, by the person under
whose name it is or is to be supplied, to be used for human
beings
for the purpose of one or more of the following:
I.
diagnosis, prevention, monitoring, treatment or alleviation of
disease;
ii.
diagnosis, monitoring, treatment, alleviation of or compensation for
an injury or handicap;
iii.
investigation, replacement or modification of the
anatomy or of a physiological process;
iv.
control of conception;
and
that does not achieve its
principal intended action
in or on
the human body by pharmacological, immunological or metabolic means,
but that may be assisted in its function by such
means; or
b.
an accessory to such an instrument, apparatus,
appliance, material or other article.
” [emphasis added]
[15]
Furthermore, the Optive range of products has also obtained the “CC”
accreditation mark as a medical device in
Europe.
[16]
The Optive range of products are further registered globally as a
medical device with the Global Medical Device Nomenclature
(“
GMDN
”)
Agency; an internationally recognized body responsible for
maintaining the GMDN codes, which is a system of internationally
agreed descriptors used to identify all medical device products.
[17]
The
South African Draft Medical Devices and IVD Guidelines 2014
in paragraph 5.7 thereof, recognise the use of the GMDN codes. The
relevant portions read as follows: —
“
GMDN
are codes used by regional or national regulatory bodies to
consistently describe medical devices. GMDN codes are used to assist
in the consistent assessment of devices before they are approved for
supply; ongoing monitoring of devices one they are available
for
supply.
...
When lodging
an application to include a device with the Council on the Medical
Device Register…, the Applicant must specify
the GMDN code
that best describes the devices that they want to include in the
Register.
”
[18]
All the above countries are considered to be so-called “benchmark”
countries by the MCC, with the results that
the standards applied in
those countries are acceptable to the MCC. In order to reach
their conclusions, these countries
were required to satisfy extensive
safety and efficacy criteria.
[19]
However, the death nail in the respondents’ coffin is the
following statement by Professor Walubo, its expert witness:—
“
In this
respect, the term artificial tears is a misnomer for most products,
including Allergan Optive product range, that identify
themselves as
such, because they do not mimic the full composition and functions of
human tears. The appropriate terms should
be “Tear
aids”.
”
[20]
Regarding the classification of the Optive products in other
benchmark countries as medical devices the laconic response from
Professor Walubo is “
(w)ith clearer
(sic)
evidence today, it will not be surprising if these products are
reclassified as medicines by these agencies
”.
This has not been done to date and the court is not inclined to
override the expertise of experts in so many countries
until they,
themselves, believe it necessary to reclassify the Optive range of
products. Given the fact that the eyes of
a human is of
cardinal importance, one can reasonably expect that the benchmark
countries are extremely vigilant regarding eye
products and would
react to the smallest negative feedback regarding side-effects or
complications with any product to be used
in the eye.
[21]
As pointed out by the applicant in its founding affidavit, which
facts are not disputed by the respondents, the applicant’s
Allergan product range contains carboxmethylcellulose (“
CMCS
”)
Levocarnitine, erythritol, glycerine, electrolytes and water.
These facts are admitted by the respondents.
[22]
As pointed out by the plaintiff’s expert Dr Christophe Baudouin
(the Editor-in-Chief of the
French Journal of Ophthalmology,
the Secretary General of the French Society of Ophthalmology and a
member of several international societies, including the prestigious
American Ophthalmological Society and the Academia Ophthalmologica
Internationalis), the mode of action of CMCS is based on it
physical
properties which provide a lubricating effect and prolonged residence
time in the eye. CMCS increases viscosity
and has
pseudo-elastic (i.e. shear thinning) properties.
[23]
According to Dr Baudouin the mode of action of glycerine in eye drops
is also based on its physical properties with no pharmacological
receptor-mediated properties. In the US, glycerine is described
as an ophthalmic demulcent – an agent which is applied
topically to the eye to protect and lubricate mucous membrane
surfaces and relieve dryness and irritation.
[24]
Studies have shown that hydrogenated castor oil may be used to
enhance the stability of moisture-sensitive drug products.
[25]
Regarding the ingredient sodium hyaluronate, Dr Baudouin testifies
that it is the predominant form of hyaluronic acid at physiological
pH. He testifies that it is useful for enhancing the
availability and retention time of drugs administered to the eye and
that it is immunoneutral which makes it useful for the attachment of
biomaterials for use in tissue engineering and drug delivery
systems.
[26]
Erythritol, is a suitable carrier for actives in sachets and
capsules, and as a diluent in direct compression tableting.
Dr
Baudouin testifies that erythritol is included in the formulation of
the Optive range of products as a tonicity agent/compatible
solute.
[27]
Osmoprotection (cell hydration) or normalisation of cellular function
in the presence of osmotic stress, is achieved in almost
all
organisms studied by synthesis or accumulation of small organic
osmolytes that may be termed compatible solutes.
[28]
Recent research has demonstrated that replacement of salts, such as
sodium chloride typically found in ophthalmic preparations,
with
compatible solutes such as carnitine and erythritol allows ocular
surface cells to maintain normal function and water balance,
despite
the presence of the ongoing hyperosmolar tear film characteristic of
dry eye.
[29]
Dr Baudouin concludes by stating that the Optive range of eye drops
therefore have a dual mode of action – the physical
lubrication
of the eye and hydration of the corneas and osmoprotection
(hydration) by the polyols and carnitine assisting the influx
of
water into the cells on the surface of the cornea. From what he
sets out, it is very clear that the Optive range of products
does not
fall within the definition of a medical device set out above.
[30]
Dr Baudouin also testifies that, in addition, all the ingredients in
the products that make up the Optive range are included
for their
mechanical and physical activities and not for any pharmacological
properties: —
[30.1]
Carboxymethylcellulose sodium
for its viscosity-increasing,
hygroscopic and pseudo-elastic (i.e. shear thinning properties.
[30.2]
Glycerine
as solvent and also for its physical, humectant and emollient
properties.
[30.3] Hydrogenated
castor oil
for its lubricating properties.
[30.4]
Sodium
hyaluronate
for its physical and hygroscopic properties, with
hyaluronic acid being a natural and biodegradable polysaccharide in
the human
body. An average 70 kg individual has approximately
15 g of hyaluronic acid in his/her body.
[30.5]
Erythritol
and carnitine
for their osmoprotective and/or cytoprotective
properties.
[31]
Dr Baudouin’s evidence demonstrates that the Optive range of
products was first made available as medical devices in
Europe and
the United Kingdom, and was subsequently introduced in New Zealand,
Switzerland and Australia as medical devices.
[32]
It is emphasised that Dr Baudouin, himself, has had over seven years’
experience with the applicant’s Optive range
of products and
speaks from personal experience.
[33]
The findings and conclusions by Dr Baudouin have been presented at
scientific meetings and have become the accepted state-of-the-art
knowledge regarding the fact that the Optive range of products
provides lubrication of the eye and hydrates the surface of the
eye.
[34]
Dr Baudouin has participated in scientific congresses and teaching of
doctors/ophthalmologists over many years and in many
countries and
can, with certainty, state that the Optive range of products are
regarded as medical devices by the medical community.
[35]
The Optive range of products achieves its purpose by the means set
out in the definition for a medical device, and is recognised
globally as an ophthalmic and medical device, as opposed to an
artificial tear, which is the only product, in terms of the Medicines
Act, which would be subject to registration as a medicine.
[36]
It is also telling that the so-called expert evidence of the MCC,
provided by Dr Walubo, who works for the MCC and whose independence
can be questioned, is clearly defective in that it stems from a clear
misunderstanding of the definition of a medical device as
contained
in the Medicines Act. Most of his evidence is so-called “newer
facts” relating to tests on rabbits
and the like. Most of
it is hypothetical and speculative. Reference is made to the
following sentence in his affidavit
for example: —
“
(s)o,
having high gram-amounts of one ingredient (CMCS) does not mean that
the actions of the final product( Allergan Optive product
range) are
ascribed to this abundant ingredient (CMCS)
.”
[37]
Effectively what Dr Walubo seems to do is to seek for fragments of
evidence which
might
indicate that the ingredients of the
Optive range of products may have some other effect than that claimed
by the applicant.
[38]
Another telling example of his misunderstanding of the term “medical
device” is the following statement to be found
in Dr Walubo’s
affidavit: —
“
The
term ‘artificial tears’ should therefore only be used for
products that replace the function of natural tears. Such
products
may be regulated as either medical devices or medicinal products,
depending upon their mode of action.
These
products do not need to stimulate physiological functions of the
natural tears
.
The
intended effect may be achieved by physical means only
,
i.e. by washing the eye surface (effect of dust, smoke), or
supplement the aqueous layer of natural tear film with additional
water under conditions of significantly increased evaporation (dry
heat, air conditioning). By decreasing the exposure to irritants
they
may be helpful in treatment of ‘minor irritations’ of the
eye.
” [Dr Walubo’s own
emphasis]
(All of the above
“evidence” is a mélange of paragraphs uplifted
directly from the
Manual on Borderline and Classification in the
Community Regulatory Framework for Medical Devices -
but not in
sequence and also from different paragraphs from the manual. This
is clearly not the manner in which one quotes
from an article.)
[39]
None of what Dr Walubo states, causes the Optive range of products to
fall within the definition of a “medical device”.
[40]
He further ends his affidavit with conclusions not based on facts set
out in his affidavit. Once again, he prefaces his
“conclusions”
by the words “
recent evidence shows that…
”
and then sets out the following: —
“
43.1
CMS has pharmacological activity whereby it directly interacts
(binds) with the corneal epithelial cells or cellular structures,
and
stimulate gene expression which leads to improved wound healing of
the cornea. In effect, CMCS stimulates some of the
physiological functions of the natural tears.
43.2
Osmoprotectants L-carnitine, erythritol, glycerol and the
electrolytes induce their effects via pharmacological and
immunological
processes of osmosis, inhibition of mediators of
inflammation, prevent programmed cell death (apoptosis), stimulate
mitochondrial
metabolism etc.
43.3
The other components of Allergan Optive product range (L-carnitine,
erythritol, glycerol electrolytes and water) too have
pharmacological/chemical activity that contribute to the product’s
therapeutic effects, e.g., restoration of pH, osmolality,
anti-inflammatory, etc, by pharmacological/chemical mechanisms
similar to those used to restore plasma of pH and osmolality by
the
same agents after oral or intravenous administration.
”
[41]
Given that Dr Walubo has not given any credible or detailed evidence
for his sweeping conclusions (based on the research of
others) they
can be ignored without further ado. Given the deficiencies in
his affidavit it is not surprising that he sought
to introduce an
entire new affidavit at the commencement of the hearing running into
51 pages. Unfortunately for the respondents,
his affidavit was
filed wholly out of time and in filing it, the respondents implicitly
concede that the initial affidavit of Dr
Walubo did not assist them
in the slightest as it was not “detailed”.
[42]
As set out above, the respondents, in seeking condonation for the
last-minute filing of the affidavit, states that a “detailed”
affidavit is now sought to be introduced by Dr Walubo. The
court has no difficulty in rejecting the evidence of Dr Walubo
as
wholly unconvincing, speculative and mostly relying on so-called “new
evidence’ which apparently might –
in the future
–
change opinions. Until such time, the “new evidence”
has no probative value.
[43]
All that this current “evidence” consists of is, as
stated, an amalgam of fragments of so-called “evidence’,
hastily and illogically amassed. The court can only seek
guidance from his “expert” evidence and has, in any
event, found none. The
Plascon-Evans
Paints Ltd v Van Riebeeck Paints (Pty) Ltd
[1984] ZASCA 51
;
1984
(3) SA 623
(A)
rule therefore finds no application in this
matter. As was highlighted by Heher JA in the matter of
Wightman t/a JW Construction v Headfour (Pty) Ltd and Another
[2008] ZASCA 6
;
2008 (3) SA 371
(SCA)
at
[13]
–
“
A
real, genuine and bona fide dispute of fact can exist only where the
court is satisfied that the party who purports to raise the
dispute
has in his affidavit seriously and unambiguously addressed the fact
said to be disputed.”
[44]
No such real, genuine and
bona fide
dispute of fact has been
raised by the respondents.
[45]
By way of further example, Dr Walubo seeks to contend that all the
benchmark countries, who are specialists in their field,
are wrong in
classifying the Optive range as medical devices. Contrary to
his allegation, the only country which ever classified
the Optive
range of products as medicines is Singapore. In any event, even
this contention is inaccurate. Optive MD was first
approved in
Singapore as a pharmaceutical product on 27 May 2010, and
reclassified, soon thereafter, on 11 October 2011, as a medical
device. Far from “new evidence” allegedly changing
the thought patterns of the benchmark countries, the opposite
is
true.
Is
the Call-up Notice referred to by the respondents applicable to the
Optive range of products?
[46]
The second issue to be determined in this application is whether the
Optive range of products was called up for registration
in terms of
Government Gazette
No R2179 of 28 October 1977
as medicines
in terms of section 14(2) of the Medicines Act which Call-up
notice reads as follows: —
“
The
Medicines Control Council has, by virtue of the powers vested in it
by section 14 (2) of the Medicines and Related Substances
Control
Act, 1965 (Act 101 o 1965), by resolution approved by the Minister of
Health, determined that artificial tear solutions
and contact lens
solutions are subject to registration in terms of the provisions of
the said Act as medicines falling under pharmacological
classification 34 of Category A in regulation 4 (a)
of the regulations
made in terms of the said Act,
with effect from the date of publication this notice.
”
[47]
It is emphasised that this Call-up notice only finds application
should the court hold that the Optive range is medicines.
For
reasons set out above, the court holds that the Optive products are
medical devices.
[48]
Furthermore, it should be noted that when this Call-up Notice was
published, there was no definition of a “medical device”
in the Medicines Act. Hence only medicines were subject to
Call-up Notices.
[49]
The respondents correctly concede that if the Optive range of
products are medical devices then they are not subject to
regulation.
However, as stated, they contend that the Optive
range of products are medicines.
[50]
This court has held that the Optive range of products is not
medicines as defined in the Medicines Act and hence the Call-up
Notice does not find application. In the matter of
Treatment
Action Campaign and another v Rath and others
[2008] 4 All
SA 380
(C)
at paragraph 31, it was also pertinently held that it
is not for the Medicines Control Council to decide whether a
substance is
a medicine, but that it is a question to be decided by a
court: —
“
The
question whether or not any particular substance is a medicine must
be determined with reference to provisions of the Act and
when its
identity is questioned. The attributes of the substance and the
claims made in respect of the substance will determine
if it is a
medicine within the meaning of the Medicines Act.
The question
for determination is whether VitaCell is subject to registration as a
medicine. The answer to this question will
turn on the
interpretation of the 2002 call up notice. I agree with Mr
Budlender’s submission that it is not for the MCC
to decide
whether the substance is a medicine.
It is for
the courts to decide that question
.”
[emphasis added]
[51]
As has been stated earlier in this judgment, the Optive range of
products are universally recognised as medical devices, namely
ophthalmic lubricants, as opposed to artificial tears.
[52]
When one analyses the Call-up Notice, in the manner prescribed by
Wallis JA in the matter of
Natal Joint Municipal Pension Fund v
Endumeni Municipality
2012 (4) SA 593
(SCA)
at
paragraphs [17] to [27], it refers only to “artificial tear
solutions” and not ophthalmic lubricants.
Conclusion
:
[53]
Given what has been set out above, the Optive range of products are
medical devices and not subject to registration, absent
any
regulations to do so.
Order
[54]
In the premises the following order is made: —
1. The products
identified in annexure “
FA1
” to the founding
affidavit (“the Optive range of products”) as emanating
from the applicant are medical devices
as defined in section 1
of the Medicines and Related Substances Control Act 101 of 1965.
2. In the absence of
the promulgation of appropriate regulations in terms of
section 35(1)(xxvii) and/or (xxviii) of the Medicines
and
Related Substances Control Act 101 of 1965, the first respondent
and/or the second respondent, are not empowered to deal with
the
authorising, regulating, controlling, restricting or prohibiting the
registration, manufacture, modification, importation,
exportation,
storage, transportation, sale or use of the Optive range of products
in respect of its safety, quality and efficacy
in the Republic.
3.
The Optive range of products are not subject to: —
3.1Registration in
terms of section 14(2) of the Medicines Act; and the
3.2
Government
Gazette
5790 dated 28 October 1977 (promulgated in terms of
section 14(2) of the Medicines and Related Substances Control Act 101
of 1965)
determining that artificial tear solutions and contact lens
solutions are subject to registration in terms of the Medicines Act
as medicines falling under pharmacological classification 34 of
Category A in regulation 4(A) of the regulations made in terms
of the
Medicines Act (“the Call-up Notice”)
4. The first and
second respondents are forthwith directed to release all and/or any
of the Optive range of products detained by
them, including
specifically the products listed in the table annexed marked “
FA5
”
to the founding affidavit.
5. The Respondents
are ordered, jointly and severally, the one paying, the other to be
absolved, to pay the costs of this application,
including the costs
of two counsel where engaged.
JANSEN
J
JUDGE
OF THE HIGH COURT
For
the Applicant
Advocate AC Botha
Instructed
by
Goldman Judin Inc
(Ref: Mr Judin/R Hsiao/A0005 -011 –
595 2300)
For
the Respondents
Advocate W.R.
Mokhari SC and Advocate H.A. Mpshe
Instructed
by
The State Attorney
, Pretoria (Ref: 0084/2015/Z64/jb -
012-309 1623)