The PHD Chamber of Commerce & Industry (
PHDCCI) has submitted a representation to the Expert Committee headed by Dr. C.
K. Kokate, Chairman, Expert Committee, Directorate General of Health Services,
(DGHS), Ministry of Health and Family Welfare, Govt of India, in regard to the
replacement of Gelatin Capsules with Cellulose Capsules as also the safety and
vegetarian or non vegetarian aspects concerning Gelatine capsules versus HPMC
capsules.
It may be noted that the DGHS vide notice
dated June 02, 2017, had sought views of various stakeholders to address all
the technical issues pertaining to replacement of gelatin capsules with
cellulose based capsules for encapsulation of drugs.
The notice states that “A proposal has been
received to replace gelatin capsules with cellulose based capsules which are of
plant origin and are safe for use as compared to animal based gelatin
capsules”.
Ministry of Health and Family Welfare vide
order dated 20.03.2017 has constituted an Expert Committee to address all the
technical issues pertaining to replacement of gelatin capsules with cellulose based capsules for encapsulation of
drugs.
The Committee has desired that views of
stakeholders including manufacturers/marketers of HPMC capsules as well as NGOs
who are working in this area or involved in this subject may also be obtained
so that a considered view can be taken in the matter. In order to examine the pros and cons of the
proposal, suggestions/comments are invited from the Stakeholder/NGOs/Consumers
within 21 days.
“In the meanwhile, soft gelatine capsules
have been given a go-ahead, therefore there is no prima facie issue with the
raw material and hence the replacement of the hard gelatine capsules being
non-vegetarian is totally misplaced and uncalled for”, said Vivek Seigell,
Director, PHD Chamber of Commerce & Industry said that the PHDCCI,
In this connection, at a meeting of the
Technical Advisory Board (DTAB) of the CDSCO (the apex body to decide on
technical issues) on May 13, 2016, a proposal to label cellulose based capsules
with a green dot to indicate its vegetarian origin was considered. The DTAB
turned down the proposal for the required amendment of the Drugs &
Cosmetics Act on the basis that unlike in the case of food items, the choice of
drugs is not that of the consumer (the patient) and is based on the
prescription of the doctor where considerations of vegetarian origin or animal
origin has no relevance. DTAB also recorded its observation that HPMC capsules
are made from a semi synthetic chemical and hence cannot be considered of
vegetarian origin.
The Supreme Court, in its order dated March
07, 2013, Case No. 641, had ordered that there is no need for non-veg or veg
labels on drugs or cosmetics and hence even the red dots which are printed on
non-veg products was not implemented for medicines.
According to Vivek Seigell, Director, PHD
Chamber of Commerce & Industry, Gelatine Capsules are consumed by people at
large as carriers of important medicines used to cure many terminal and
lifestyle diseases. The consumption of medicine is more curative than out of
personal choice. Looking at basic fundamental, it is not prudent to enter the
Vegetarian and Non-Vegetarian debate in this matter. It may further be noted,
that Gelatine used in the manufacture of empty capsules are derived from an
extraction process wherein no animals are harmed or killed for this specific
purpose. Only the left over bones having hydroxide and collagen, which is a
protein widely found in animal bones (and is not more than 2% of the total
value of the dead animal) is extracted through sophisticated machineries in WHO
GMP approved extraction and manufacturing plants. Accordingly it is misplaced
to have any notion that Gelatine Capsules are non-vegetarian in origin.
Gelatine capsules are totally safe for human
consumption. WHO as per evidence certifies Empty Hard Gelatine Capsules for its
total safety for Human Beings. And so do the Pharmacopoeia of USA, Japan, European Union, United Kingdom, Australia and
India.
When a scientific body of the Government of
India, the Indian Pharmacopoeia Commission, publishes a monograph on gelatine
and empty gelatine capsules how can it then be unsafe? Presumably, the ultimate test of safety of a
product is if it conforms to the specifications given in a pharmacopoeias,
Several other pharmacopoeias around the world, including the British
Pharmacopoeia, the United States Pharmacopoeia, and the Japanese Pharmacopoeia
have confirmed its safety.
Inspite of the repeated requests Professor
Kokate’s committee has not yet replied to stakeholders as to why gelatine
capsules are less safe than HPMC (cellulose) capsules and what is the
scientific and technical evidence for the same, if any.
“Across the globe over 95% of capsule
formulations are gelatin capsules and even among the rest 5%, HPMC is primarily
used for nutraceutical formulations. In India only around 2% capsules are HPMC
based and almost all of them are nutraceuticals”, said Vivek Seigell. He
further added that no cellulose capsules are used for products such as
antibiotics, oncology, anti-infectious, painkiller and other medicinal
categories. Nor have any tests been carried out by the DCGI in India whether
such medicinal products would maintain their stability, bio-availability,
bio-equivalence and other properties if filled in Cellulose capsules.
Technically speaking:
·
Pharmacokinetics and Pharmacodynamics properties of the drug has to be
tested before it is put in to the market if the drug is encapsulated in
Cellulose Capsules
·
Bioequivalence study for each drug would have to be carried out also
· HPMC capsules are not suitable especially
if the medicine has Potassium ions.
Similarly for a few of the drugs, Cellulose capsules were better than
Gelatine capsules
·
At the same time a study of end of shelf life performance for cellulose based
capsules needs to be conducted and, hence, the issue of replace of Gelatine
should not be taken hastily
·
The time taken for the above tests of bioequivalence of thousands of
drugs and combinations and Pharmacokinetics and Pharmacodynamics properties
will take several years followed by the long process of approval from the drug
authorities and any such move could mean devoiding the 1.2 billion people of
this country of basic medical and health services for that many number of
years.
Following
are the pointwise clarifications detailing the Myths and the Reality:
MYTH -1
HPMC CAPSULES ARE USED EXTENSIVELY IN MANY
COUNTRIES
Reality
Over 95% of capsule formulations are gelatin capsules and even among the rest 5%,
HPMC is primarily used for nutraceutical formulations the World over . In India only around 2% capsules are HPMC based
and almost all of them are nutraceuticals.
MYTH -2
HPMC IS SAFER THAN GELATIN
Reality
Gelatin has been used for hard and soft
capsules over the last 100 years and so far there has been practically no reports of severe or even moderate adverse
effects. On the other hand HPMC for Hard Capsules are of recent origin. Unlike
in the case of production of Gelatin, HPMC manufacture involves use of reagents
and chemicals, some of which are potential carcinogens, in a multi step process.. The track record of HPMC use is just a decade
or even less and therefore it is difficult to predict safety over time.
MYTH -3
HPMC OF THE RIGHT GRADE IS READILY AVAILABLE
Reality
The limited use of HPMC in India is dependent
on imports (mostly from China) and it is not clear whether new generation HPMC,
recommended for capsules is readily available and if they are, at what prices.
MYTH-4
REPLACEMENT OF GELATIN BY HPMC DOES NOT
REQUIRE NEW REGULATORY APPROVALS
Reality
Any change of formulation and introduction of
a new material or excipient is considered a New Drug under Schedule Y of the
D&C Act. That means that every replaced formulation (with HPMC) of every
API needs to be validated for safety, efficacy and pharmacokinetic parameters
of dissolution, disintegration, release and
stability through fresh pre
clinical and/or clinical investigations. In fact if all hard gelatin capsules
in the market ( close to 20,000 packs) are to be replaced, it will take several
years to get them tested and approved and costs would be enormous and that too at a time when every one is attempting
to reduce healthcare costs to make it
more affordable for the masses.
MYTH- 5
CHANGE OVER TO HPMC WILL NOT ADD TO HIGHER
COSTS OF THE CAPSULE FORMULATIONS
Reality
At present prices of HPMC , it is estimated
that the costs of production of HPMC
capsules will be considerably higher and
so too prices. The new generation HPMC which is preferred for use in capsules
is still patent protected and hence patent holders will have monopoly on
prices.
MYTH – 6
ANIMALS ARE SLAUGHTERED FOR RAW MATERIAL
(BONES, HIDES, FISH SCALES ETC. ) TO MANUFACTURE GELATIN
Reality
Raw materials used are waste products of animals and animal derived foods,
which are environmentally unsafe and
difficult to dispose off . Converting them to Gelatin and derived products adds
value to waste material and offers solution to waste disposal issues. No animal
is slaughtered for manufacture of Ossein, Gelatin and derived products
MYTH – 7
HPMC IS PLANT BASED AND THEREFORE NATURAL
Reality
While HPMC is based on Cellulose to start
with, it undergoes chemical reactions involving building of new covalent
linkages and hence is a chemical by definition and not a natural material
MYTH – 8
PRESENT PLANT AND MACHINERY CAN BE UTILIZED
FOR MANUFACTURE OF HPMC CAPSULES
Reality
The process being different, considerable
modification and fresh investments in new machinery would be required to
produce HPMC capsules
With the stoppage of Gelatine Capsules, both
Cellulose capsules and Cellulose raw material will have to be imported at huge
foreign exchange cost mainly from China, there by further increasing our
dependence beyond the APIs which itself is quite precarious. Additionally the capacity to supply HPMC
capsules simply does not exist from overseas manufactures.
Vivek Seigell also pointed out that if it is
an issue of non-vegetarian versus vegetarian capsules, then it should be noted
that there has never been a bias against non-vegetarian sources in the
manufacture of medicines. Products from non-vegetarian sources are currently
widely used in many segments of pharmaceutical industry.
Gelatine is used in Blood plasma substitutes,
Haemostatic sponges, Surgical implants, Hydrocolloidal dressings, Collagen for
skin cream and Dietary supplements, certain food colours, vaccines, apart from
auxiliary treatment for degenerative arthritic diseases and many other
products, including a large number of food products.
95% of the Gelatine manufactured in India is
produced by the PHDCCI Association members.
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