The debate over gelatin capsules vs plant-based capsules (Cellulose) has garnered a lot of attention from all stakeholders of the lifesciences industry. The discussion began almost a year back when Maneka Gandhi, Union Minister for Women and Child Development made a ‘representation’ to the Health Ministry on completely replacing gelatin capsules with plant-based capsules following a request received from the Jain community to create an option so that consumers can not be forced to use capsules made from animal tissues.
JP Nadda, Union Minister of Health and Family Welfare discussed the matter with the Drug Controller General of India (DCG(I)), Dr GN Singh and and then Health Secretary, Bhanu Pratap Sharma to look into the matter on a priority basis. However, the matter wasn’t taken up at the Drug Technical Advisory Board (DTAB) and failed at the initial proposal itself. However, lately the debate has regained steam and now an expert committee set up by the Health Ministry has asked all stakeholders to share their views on the matter.
However, it is an issue with wide-ranging implications. Some of the major questions that the situation throws up include:
Industry leaders and veterans share their views on these issues and highlight the different aspects of such a switchover.
Question posed to MoH&FW in the LOK SABHA
Unstarred question no: 2081, Answered on: 28.07.2017, Jayadev Galla-TDP-Teleana
Will the Minister of Health and Family Minister be pleased to state:
(a) whether the types of cellulose capsules that are presently available in the market are different from animal based gelatin capsules, if so, the details thereof;
(b) whether switching over to vegetarian cellulose capsules will hit the Rs 5000 crores gelatin capsule industry;
(c) if so, the details thereof; and
(d) the action taken by the Government to address the problem?
Answered by Faggan Singh Kulaste, the Minister of State in MoH&FW
(a): Yes. Presently, cellulose capsules are prepared from HydroxyPropylMethyl Cellulose (HPMC), which is synthetic in origin, whereas Gelatin Capsules are prepared from gelatin which is a purified protein obtained by partial hydrolysis of animal collagen
(b) to (d): The Government has not received any such report that switching over to vegetarian cellulose capsules will hit the Rs 5000 crore gelatin capsules industry. However, some industry associations have raised certain issues including technical issues and economic viability for replacing gelatin capsules with cellulose capsules. The government has, after examination of all pertinent issues relating to use of gelatin capsules and its replacement by cellulose based capsules, already constituted a Committee to consider all pertinent issues and make recommendations to the Government.
‘Consumption of medicine is more curative than out of personal choice’
Gelatin 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 fundamentals, it is not prudent to enter the vegetarian and non-vegetarian debate in this matter. It may further be noted, that gelatin 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 leftover bones having hydroxide and collagen, which is a protein widely found in animal bones (and is not more than two per cent of the total value of the dead animal) is extracted through sophisticated machineries in a WHO-GMP approved extraction and manufacturing plants. Accordingly it is misplaced to have any notion that gelatin capsules are non-vegetarian in 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.
In the meanwhile, soft gelatin capsules have been given a go-ahead, therefore there is no prima facie issue with the raw material and hence the replacement of hard gelatin capsules because it is non-vegetarian is totally misplaced and uncalled for.
Across the globe, over 95 per cent of capsule formulations are gelatin capsules and even among the rest five per cent, Hydroxypropylmethyl cellulose (HPMC) is primarily used for nutraceutical formulations. In India, only around two per cent capsules are HPMC-based and almost all of them are neutraceuticals. 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 retain their stability, bio-availability, bio-equivalence and other properties if filled in cellulose capsules.
– Vivek Seigell, Director, PHD House
‘IDMA would not recommend change from Gelatin to Cellulose’
We have taken up the matter with the Health Ministry and DCGI. We also had a meeting with Nripendra Misra, Principal Secretary to PMO on July 18, 2017 in New Delhi and explained to him that change over from gelatin capsules to cellulose capsules in no way would benefit our Indian population. He asked us as to how much time industry would require to change over, to which we put forth our logical arguments as mentioned below. Finally, he was of the opinion that both types of capsules should co-exist. We therefore request the government to continue to allow the use of gelatin capsules to ensure availability of safe, efficacious and affordable drugs to the patients.
– Daara B. Patel, Secretary-General, IDMA
‘We should not bring religious sentiments into medication and health needs of patients’
Patients have the right to choice based on credible information . I recollect when we were debating on vegetarian and non-vegetarian labelling of food products derived from non-vegetarian ingredients in the food to enable consumers to make an informed choice. Even during those days in 2003-4 the issue on medicines was raised but the policy makers made sure that we do not confuse the consumers on such issues which concerns their health and medication to treat disease.
Now again we find commercial considerations and profit motives are over-riding the need for health and safety of consumers by debating on gelatin capsules vs cellulose capsules. Consumers do have the right to choice but we should be careful while communicating the message as it should never mislead the consumers on quality and safety. All these years, scientists always promoted gelatin-based capsules and never tried to differentiate between gelatin and cellulose capsules to ensure we do not compromise on accessibility and did not bring religious sentiments into medication and health needs of patients. Why this sudden debate in public domain, especially in a country where citizens are denied treatment due to high out of pocket expenditure on medicines. This is certainly not an appropriate time for India to further confuse the Indian consumers who are already struggling to access safe and quality healthcare by differentiating between gelatin and cellulose aapsules. We should close this debate right away and enable consumers to access medicines in the most scientific manner rather than raising concerns which are not in the interest of Indian patients.
– Bejon Kumar Misra, Founder, Consumer Online Foundation
‘It is necessary to relook the issue of veg v/s non-veg capsules w.r.t. technical, regulatory & economic aspects’
The whole issue of animal vs vegetable origin capsules needs to be looked at objectively.
A major limitation with gelatin capsules is moisture sensitivity; second drawback is cross linking in presence of aldehyde compounds, resulting in variations in DT and dissolution profiles. HPMC capsules, on the other hand have a much lower moisture content (almost one-third) compared to the gelatin shell, making it compatible with hygroscopic materials, and providing better stability under a wide range of environmental conditions. In case of HPMC capsules, there are two major limitations. First is the low correlation between in-vitro dissolution/ disintegration and in vivo performance, in comparison to gelatin capsules, attributed to interaction between in-vitro testing media (especially potassium ions and temperature) and HPMC capsule gelling systems. Thus, developing an in-vitro dissolution tests for HPMC capsules is more challenging. Another issue is that machine ability of HPMC capsules differs from hard gelatin capsules; modifications in processing and the need for gelling systems is important to get proper capsules of desired specifications and avoid higher rejection when used in filling machines.
Monographs and regulatory guidelines for HPMC capsules are still under review and consideration. Reformulating the existing gelatin capsule products to HPMC capsules will entail a rigorous exercise of change control with regulatory impact with a battery of evaluations – compatibility studies with HPMC capsule material, physicochemical characterisation, including in-vitro release studies; stability assessment; package suitability; scale up batches etc. and in certain cases repeat of high cost bio-equivalence studies. This would then be followed by variation filing with regulatory agencies requiring prior approval.
HPMC capsules are three to four times more expensive compared to gelatin capsules. The change control protocol and testing for regulatory approval will involve an economic burden. The current installed capacity for HPMC capsules is very marginal, only around two per cent compared to gelatin capsule manufacturing capacity. Thus, there is a very big gap to be filled to completely replace gelatin capsules, again a highly cost-intensive issue. In conclusion, it is necessary to relook the issue of veg v/s non-veg capsules w.r.t. technical, regulatory and economic aspects and not be swayed by religious sentiments. In a developing country, delivering cost-effective medication is of utmost importance. Time tested gelatin capsules need to stay. HPMC capsules can be an option for new products under development; they are more advantageous for inhalation products where the inhalable fraction is better with HPMC capsules, and for drugs having compatibility problems with gelatin. More regulatory guidelines are awaited for HPMC capsules to expand their usage in future; further improvements needed in HPMC capsules to increase their utility are machinability and better correlations in IVIVC.
– Dr Mala D Menon, Professor of Pharmaceutics, Bombay College of Pharmacy
The Debate is not About benefits but religious sentiments
Having just barely grappled with generic drugs, price capping and yoga, patients now have a new dilemma – ‘Should I ask my physician whether the capsules he prescribes are gelatin or cellulose?’ For most patients in India who were unaware of the coating around their capsules, this is a new and interesting debate. The dialogue is not about which is more beneficial and cheaper but of one which revolves around vegetarian vs non – vegetarian and apparent religious sentiments attached to it.
Gelatin capsules are cost-effective but are not stable when exposed to heat or humidity and could present serious storage problems with the capsules. Gelatin capsules are appropriate when using powdered supplements, but would not be advisable when using a liquid or gel format. On the other hand, the vegetarian capsule is created using cellulose, which is naturally derived from plants. The vegetarian capsules provide a very natural delivery system for the supplement ingredients and still allow the rapid delivery of the contents to the body.
Vegetarian capsules has no threat of negative health risks, even when consumed in higher volumes and over the long term. Globally, gelatin capsules have been time-tested and are held to be safe and are recognised by regulatory agencies across the globe. That over 95 per cent of all capsules in world are gelatin ones is strong evidence supporting these. Gelatin capsules have been used for many years and pharma companies with presence in markets across the globe have their compounds delivered in gelatin capsules. As compared to gelatin capsules, the number of cellulose capsules that have been approved is significantly less. Switching over to ‘pure-veg’ capsules will lead to an increase in the cost of associated medicines, according to experts apart from the change in technology and sourcing of raw materials that would require time and planning.
The Health Ministry is looking to replace gelatin capsules with cellulose-based ones and has set up an expert committee to look into the matter. It has invited all stakeholders to send their suggestions and comments. The patients do not have a very big voice but would definitely like the medicines to be within their reach and as long as the price of medicines is not affected or there are no supply disruptions, the coating hardly mattered. ie until now. This debate ignites questions in many people’s minds. The seemingly innocuous capsule has assumed a religious colour and there are strong sentiments that the origin and use of animal products without appropriate warnings leads to cheating and duping and playing with the emotions of people. The government’s decision will therefore find popular acceptance amongst the patients and their families. It remains to be seen however, as to how the price will be kept in check and the transition managed. Until then, the religiously-conscious patient will continue to pop in the gelatin capsule and have office and neighbourhood debates based on religious and political affiliations.
– Ratna Devi, CEO DakshamA Health, Founder Indian Alliance of Patient Groups (IAPG)
Discontinuing only hard gelatin capsules will be an outright non-tenable discrimination
The Ministry of Health and Family Welfare (MoH&FW) has set up an expert committee inviting suggestions from stakeholders about the possibility of replacing hard gelatin capsules with cellulose-based capsules. The government feels that hydroxypropylmethyl cellulose (HPMC) capsules may be safer than hard gelatin capsules. This is an unwarranted concern as hard gelatin capsules are thoroughly tested by MoH&FW and experts have been able to produce a monograph on the product in Indian Pharmacopoeia, as exists in several International Pharmacopoeias. Their specification guarantees the safety of the product for human consumption.
Stakeholders are of the opinion that despite several requests, there has been no explanation from the government on any scientific reason why this matter has been raised. Hard gelatin capsules have been used around the world for over a 100 years, with no untoward health consequences reported. On the other hand, HPMC capsules are hardly used at all as an edible container for medicines. Almost all of it is used for nutraceutical products. Therefore there is no history nor evidence of the continued potency of a drug after packing in HPMC capsules. Trials need to be conducted on disintegration, dissolution, stability, potency and bio-equivalence over the complete shelf life of each formulation. There are thousands of such formulations. If adverse reaction between HPMC capsule shell and varied ingredients of the formulation exist, there may be chances of discolouration, or loss or gain of moisture, or loss of potency of the medicine.
For life saving medicines, this is a risk as the pharma industry is not likely to be held responsible for, whatever may be the final decision of the expert committee. There is a feeling in some quarters that this matter has surfaced due to vegetarian sentiment. The Drugs Technical Advisory Board (DTAB) in one of its earlier meetings had minuted that drugs are prescribed by doctors to save lives and marking them as vegetarian or non-vegetarian origin is not desirable. An earlier Supreme Court ruling has also concluded that it is not desirable to label life saving drugs as of vegetarian or non-vegetarian origin and it should be left to medical practitioners to decide what is appropriate for a patient.
– Ajit Singh, Chairman, ACG Associated Capsules
‘Gelatin-based capsules have passed the test of time’
Medicine is administered to living beings for preventive and curative purposes. It is almost never consumed as ‘food’. Accordingly, the proposition to bracket medicine with food is misplaced, which may have severe ramifications and dire consequences. This has also been acknowledged several times by the DTAB, the technical committee housed in the Health Ministry. Additionally, even the Supreme Court of India, has ruled favourably for this cause.
The primary and foremost objective of the healthcare industry is to safeguard and promote healthy living. Availability and accessibility of safe, pure and effective medicines are prerequisites and enablers to help meet this mission statement. Under no circumstances can science be mistaken for or compromised for any kind of sentiment.
The idea of ‘replacing’ gelatin capsules with HPMC has no scientific backing. Gelatin capsules have been used across the world for administering the requisite dosage forms for over 140 years without any adverse reports on life due to consumption of these capsules in either of the dosage forms – hard or soft. Its specifications are well documented across all pharmacopoeias of the world. The long lineage of the gelatin capsules is a testimony their safety, purity and efficacy. This is further enforced through regulatory specifications of its monographs which are duly scrutinised and adopted by all food and health authorities across the world.
Gelatin-based capsules form close to 99 per cent of the total capsule dosage which is available across the world. This vast usage serves as a stamp of acceptance by the pharma and nutraceutical majors who readily use this carrier to encapsulate a wide range of formulations for a plethora of curative and preventive reasons. The gelatin based capsules have not only passed the test of time, but have also been widely tested and researched on for their stability, dissolution and disintegration profiles under various conditions and for a varied set of formulations. The pharmacokinetics and pharmacodynamics are well documented for gelatin capsule formulations. We cannot, under any circumstance, put these tests to question for any reason other than those which have a scientific merit to them.
Furthermore, HPMC capsules are anyways available today, albeit in an extremely small quantity. The user has a choice even today. Given this, where is the case for thinking about any replacement? Any such deliberation is fraught with the risk of uncertainty as there is no scientific testing or data to establish the regulatory compliance of HPMC material as a carrier either today or over an extended period of time. Without proven data, tinkering with well – established drug delivery systems is an idea best left unchartered.
– Ishan Khaitan, President, Operations and Marketing, Sunil Healthcare
The switchover should not be taken as a knee jerk reaction
These are some of the merits and demerits of both gelatin and vegetarian capsules. Although the scale might tilt towards vegetarian capsules in a certain way, one cannot lose sight of the track record and the safety profile exhibited by gelatin capsules over years (more than five decades).
The switchover should not be taken as a knee jerk reaction and should be done gradually as this might pose some situations which are not palatable. For instance:
1. Entire documentation procedure in the dossiers and data systems have to be withdrawn and rectified possibly, which is a colossal job.
2. Could bring in an economic collapse on the existing manufacturers which has served the society for decades across the globe. Should this happen?..
3. Various modifications and advances adapted in the present gelatin capsule could be frittered away without any consideration. They were all patient friendly advances in terms of disintegration and dissolution.
4. Is it really a problem of acceptance? Or is it a case vested interests that loom over the debate?
My recommendation is that both should be accepted by manufacturers and the option should be left to the manufacturer and consumers as per merits. Moreoever, a slower transition with reasonable timelines should be allowed for a switch over.
– SR Vaidya, Director, BlissGVS Pharma