 "Dr Piyush Gupta, associate director, GNH India")
Since the advent of the pharma industry, the primary source of origin for drugs was synthetic chemicals. These were either derived from petrochemicals, plants or animals - primary process involved converting the active ingredient into a synthetic chemical to be used as tablets, capsules, injections etc.
At the turn of the century, due to high instances of drug resistance such as antibiotic resistance, increased side effects and India reaching the threshold limit in synthetic chemistry, the R&D process started looking for the next ‘frontier’. The next ‘frontier’ was found in medicines derived from living cells, which were not synthetic chemicals but were derived from biological sources. This was the birth of the biologic industry which went on to produce some blockbuster multi-billion dollar drugs. One of these drugs is Humira - an all-time highest selling biologic drug with sales of over $ 8 billion per year.
When a copy of a biologic is made (also called as a generic), it is called a biosimilar (bio - derived from biological sources; similar - because it’s a similar, not a copy). A biologic drug cannot be produced in an exact copy like a generic, but it can be made alike to produce similar effects as of the original drug.
The process of biologic drug development is extremely expensive, cumbersome and time consuming. For example, if a synthetic drug development process can cost $ 200 - 500 million, a biologic is in the range of $1.8 - $ 2 billion (Refer: Table 1). There is a lot more emphasis on safety, efficacy, and quality in a biologic due to the fact that live ingredients are dealt with. Several multi-centre and multi-location trials need to be conducted in order to establish replicable QSE profile (quality, safety, and efficacy).
In the process of developing biologic or biosimilars, comparators come into the picture. Comparators are reference drugs – these are either market leader in case of new biologic developments or the innovator brand (original drug) in case of biosimilar development. Whether a new biologic or a biosimilar is being developed, a road map is needed. In a biosimilar development, one is aware of the final destination to be reached, so comparators are used at every step to verify that the progress is in the right direction. Without a comparator, it is like being lost in the sea without a map, compass or any navigation tools.
Table 1: Cost of drug discovery & development
On an average, a biosimilar development process consumes comparators worth $ 10 - 12 million. If even the most basic number in India is considered, ie the top 10 pharma companies developing a minimum of 10 biosimilar products each, the demand for comparators is upwards, ie $ 100 million per year. All this business from India is going to the foreign suppliers.
The import process is skewed in favour of foreign suppliers too, as the Indian supplier of comparator has to disclose all the details of foreign suppliers to the biosimilar developer, in order to apply for Form 11 import test permit. Of course, we do not see the developer coming back to us after the first application. There are Indian companies with in-depth knowledge of comparator sourcing and world class infrastructure to support it, but due to factors mentioned above, very little business comes to Indian companies.
Dr Piyush Gupta, associate director, GNH India
SRA (stringent regulatory authorities) markets are matured markets with a well-developed health insurance infrastructure, ie the patients get compensated by the insurance companies. But the developer does not get any compensation and has to pay the full value. Due to this fact, the prices of any given brand is always higher in a SRA market as compared to an emerging market.
Since emerging markets lack a well-developed health insurance infrastructure, the products are available at a marginal cost so that they are affordable. It is a well-known fact that many medicine brands are cheaper in Asia as compared to EU or USA. At the same time, it is rarely known to general public that a manufacturer has to prove to the regulatory authorities of each market, that the brand being sold here is the same as being sold in the country of origin.
For example, if brand Humira is manufactured in Germany, AbbVie will have to prove to Indian CDSCO by certificates, such as CoPP, that Humira sold in India will be the same as sold in Germany.
A CoPP is an official state declaration, issued by the regulatory authority under guidelines prescribed by WHO. Keeping in mind the above facts, it is easy to conclude that the quality of original branded pharma products sold in emerging market is same as in SRA countries. But, due to the lack of insurance market, the products available in emerging markets are at a far more competitive price.
The benefit to developers, sourcing from emerging markets, are ease of availability in large quantities as the same are generally more populous. Emerging markets have an availability of multiple batches which is an important requirement to build QTPP (quality target product profile). Sourcing close to the R&D centre or home country reduces the logistics cost and transport times. Also, most of the biologic products are temperature sensitive. Reduced travel time, in return, leads to considerable savings in temperature controlled logistics, which can be quite expensive.
To conclude, the objective of biosimilar development is to reduce cost and introduce a similar option quickly in the market. Smart sourcing of comparators can help achieve both the objectives and thereby benefiting the patients in terms of cost. This can be a true patient centric ideal in today’s society.
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Dr Piyush Gupta is the associate director in GNH India
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Dr Piyush Gupta is the associate director in GNH India
