If the government has its way, pretty soon medicines will also be classified as pure vegetarian. A proposal within the government seeks to replace all capsules using gelatin hard shells with cellulose shells.
Gelatin is obtained from bones of bovines and in India, mostly buffalo bones are used to manufacture it. Though it is totally detoxified and treated, there is a lobby within the government which is pushing the idea that as it is obtained from non-vegetarian sources, it can offend religious sentiments of many patients in India. In contrast, cellulose, the alternative suggested, is obtained from totally ‘vegetarian’ sources.
In March 2016 the Drug Controller General of India (DCGI) issued a notice stating that it has received a proposal for switching gelatin capsules with hydroxypropyl methylcellulose (HPMC) or cellulose capsule shells. The notice has caused panic in the Indian pharmaceutical industry because if implemented, it will raise the cost of production and increase the price of medicines significantly.
Interestingly, till date there is no clarity on where the proposal came from. The government and DCGI have not made the proposal public.
The matter also went to the Drug Technical Advisory Board (DTAB) under the health ministry, which said that medicines should not be categorised as ‘red’ (non-vegetarian) or ‘green’ (vegetarian) and the matter should be status quo. It added that since the matter involved other ministries, a broader discussion on the subject was required.
Since then, multiple representations have been made before the DCGI from pharmaceutical companies and apex industry chambers, who have all stated that doing away with gelatin will be of no benefit. It will impose additional costs on medicine manufacture and may also have adverse effects on the human body.
In March this year, the government set up the 12-member Dr Chandrakant Kokate committee to look into the issue and make recommendations. The committee met only once in May and has not reached a decision yet.
Cellulose costs 3-4 times more than gelatin and industry experts say the additional costs will be passed on to the consumer. Also, the pharmaceutical industry has already made significant investment in gelatin-based medicines and will have to make huge investments if it has to shift to cellulose.
“If implemented, cost of medicines will go up and it will be passed on to customers. To make the shift to cellulose, huge investment will be required on plant and machinery, which will also reflect on the price of the medicines,” says Daara Patel, secretary general, Indian Drug Manufacturers Association (IDMA). “Manufacturers are not ready for cellulose today. The API (active pharmaceutical ingredient) industry is struggling to get out of the clutches of China. This will push us back to dependence on Chinese companies for cellulose and raw materials. IDMA members are concerned.”
At present, India produces about 120 billion gelatin capsules per year while there is capacity for only two billion cellulose capsule shells in India. Raw material for cellulose capsules is also not available in India. With almost no capacity for the manufacture of cellulose, India will have to wholly depend on imports for this. Over 60 per cent of the capacity for making cellulose capsules is in China and that too has quality issues. The remaining 40 per cent is in the US, Europe, South Korea and Canada. Curiously, cellulose is imported into India under the category of plastics.
“If we have to shift to cellulose hard shells in India, prices will shoot up by 300-400 per cent,” says Dinesh Dua, vice chairman Pharmexil and CEO, Nectar Lifesciences Limited. “And if China pulls the plug on raw materials for this, the $6 billion industry might collapse. Relying on imports also poses a serious existential threat to the Indian Pharma industry and domestic gelatin manufacturers. It will also defeat the concept of Make in India.”
The graver issue, however, is how cellulose will behave with the medicines it is used in and what will be its impact on the human body. “Gelatin capsules have been in existence for over 100 years,” says Ishan Khaitan, president, marketing and operations, Sunil Healthcare Limited. “They have been tested with a wide variety of medicines by drug and pharmaceutical authorities and companies on safety, efficacy and purity. Gelatin has been found fit for human consumption.”
Unfortunately, the same cannot be said about cellulose. “Every drug in the generic and non-generic segment has to undergo extensive testing for ‘in vitro’ (in labs) and ‘in vivo’ for stability, toxicity and safety,” says Dua. “These tests will have to be done all over again once cellulose is allowed to be used in medicines. There is also no extended study done anywhere in the world as to how cellulose behaves in the human body and there is no regulatory pathway.” Furthermore, gelatin has a shelf life of five years while cellulose has a lower shelf life of three years.
If cellulose has to be brought in, it will have to be extensively tested from scratch, a time-consuming and expensive process. Geena Malhotra, Global Head, Integrated Product Development, Cipla, believes the choice of using gelatin or HPMC should be driven by the performance of the drug product and not imposed as a government policy. “Each product will take approximately 12 to 15 months to get medicines ready for approval with HPMC or the cellulose shell because some critical products need to be tested for specific tests,” she says. “Stability study and human bio study has to be conducted for all products in case of replacement from gelatin to HPMC or the cellulose shell.”
The ironic thing is that the government proposal prescribes that gelatin can be used in capsules for exports, while for India, cellulose capsules should be used. Also, the government has made ‘allowance’ for the use of gelatin for soft gel capsules. Even the Dr Kokate Committee that is looking into this issue has kept soft gel capsules out of its purview. Committee head Chandrakant Kokate and the Union health secretary did not respond to Outlook’s queries.
“No one knows the effects of cellulose on medicines,” says Ajit Singh, CMD, ACG worldwide, the second largest manufacturer of empty hard capsules in the world. “It has to be tested over 2-3 years through the life of a medicine. Cellulose capsules are not generally used for medicines. They are only used for nutraceuticals and herbals and form less than two per cent of our production at present. If we have to shift to cellulose, the industry will have to make substantial amount of investment.”
But most importantly, will cellulose alone solve the problem of making medicines pure vegetarian, which seems to be the main reason for the proposed shift? Industry players also point out that the use of cellulose for promoting veg medicines is itself futile as many medicines are extracted from non–vegetarian sources. “Even if you bring in cellulose to make a capsule shell vegetarian, the product inside the capsule may not be vegetarian,” says Singh. “Many medicines include extracts of liver or fish oil. In the pharma industry, blood plasma substitutes and homostatic sponges left inside the body are also made from gelatin. Even insulin is derived from non-vegetarian sources.”
The Indian pharma industry is perplexed and concerned about the future of its investment and feels that if cellulose is being pushed by the government, both cellulose and gelatin should co-exist and the choice should be left to the patients and doctors prescribing them. They also feel that if something goes wrong using cellulose, the blame will come to them. The last word is not out though as the Kokate committee is yet to take a decision on this. But if the recent history of government decrees is any measure to go by, the outcome could be predictable.