Increasing the Access to Orphan Drugs and Specialty Medicines

Dr. Piyush Gupta
Associate Director - GNH India

Organization for Rare Diseases in India (ORDI) intends to work between the Government of India and the Pharma/Biotech/Diagnostic industry to establish an Orphan Drugs Act (ODA) that will generate incentives for orphan drug developers. These acts and regulations in India will not only raise the burden off of the patients but will open the doors to the true potential of the pharmaceutical landscape in our country by giving affordable and accessible drugs to those in need.

The pharmaceutical industry is one of the most rapidly growing industries in the world and is one of the biggest contributors to a country’s economy. According to a report by the PWC, the Indian pharmaceutical industry is on the threshold of becoming a major global market by 2020. It has a growth rate of 15 to 20 percent CAGR which is expected to touch between USD 50 billion to USD 74 billion in the next decade.

Despite these astonishing numbers, India only produces low-value medicines that are either synthetic in nature which means they either have a chemical origin or a 'Biosimilar drugs' that have biological origins. While the low-value drugs are manufactured in India, the expensive high-end drugs are still being imported. There are several types of imports which take place in India which include for commercial sale, patient use, test, R & D and clinical trials. For commercial sale, India is fairly in line with the global trends as The Central Drugs Standard Control Organization (the agency which controls the imports) as we have adopted the requirements from the World Health Organization. While this system seems rational on the surface owing to the fact that all medicines need not be stockpiled in every country ; the predicament begins while importing high-end drugs for rare or orphan diseases.

India lags far behind in its endeavor to import drugs for orphan diseases. This is because the processes in place are not up to global standards, resulting in every request taking 7-8 months to process. India has a long way to go in order to get in line with the international import process. India, like any other country, has to import some such medicines that are vital for patients. The problem is further amplified with orphan drugs that are rare and are not available easily. The rules for import are clear but misunderstood by patients, doctors, and importers as there is barely any information in the public domain that advises on how to import, thereby puzzling the importers regarding the process.

Orphan Drugs and their Availability

Orphan drugs are pharmaceutical agents that have been developed specifically to treat a rare medical condition and are not easily available worldwide. The condition or disease that manifests itself in patient populations and comprise of a maximum of 6–8 per cent of the world's population is defined as rare or orphan diseases. In India, there has been a rapid growth spurt of rare diseases which are attributed to a change in lifestyle, coupled with an increase in affluence and income levels. The Indian population is now suffering from diseases that were previously unheard of a few decades ago.

Rare diseases such as infantile spinal muscular atrophy, lysosomal storage disorders, patent ductus arteriosus (PDA), familial adenomatous polyposis (FAP), cystic fibrosis, renal cell carcinoma, glioma, and acute myeloid leukemia develop at birth but manifest themselves at a later stage during adulthood. Today there are over 5000 rare diseases classified in the world. At least five new rare diseases are being reported every week in the medical literature. 80 percent of rare diseases have been purported to have genetic origins. Other rare diseases are the result of bacterial or viral infections and allergies. Some are due to degenerative and proliferative causes. These diseases are rare and the medicines for their treatment and control are not easily available or used.

In 1983, the US government passed the Orphan Drugs Act to stimulate research in the treatment of diseases that have been largely ignored by the pharmaceutical industry. Similar laws have been enacted in Japan, Australia, and the European Union. All these laws offer incentives such as shorter clinical trials, extended exclusivity, tax breaks and high rates of regulatory success. They have made it commercially attractive for pharmaceutical companies to invest in the research and development(R & D) required to find a cure for these diseases.

But even if they are incentivized to develop drugs to treat rare diseases, pharmaceutical companies remain beholden to the laws of economics and, given the low demand for orphan drugs, price these drugs as high as they choose to . For example, Rituximab, an orphan oncology drug, is the world's second highest revenue generating drug. While all this may be less of a concern to patients in Western countries, as they are covered by comprehensive healthcare plans, it forces patients in developing countries to deal with the uncomfortable realization that even though a cure exists for their condition, it is unaffordable.

Thalassemia is another perfect example of this phenomenon. Over 10 years back there would be 1 patient in 1000 that suffered from this hereditary hemolytic disease. In a matter of a few years, the number has increased ten folds as 10 in a 1000 people have reported having the disease in some form. However, for pharmaceutical manufacturers, the economics of manufacturing these drugs still do not add up. Therefore even though there is an unmet demand from patients, companies are hesitant to manufacture such high-value drugs.

This poses an interesting opportunity for India which is one of the largest manufacturing hubs in the world. The unmet demand coupled with pharmaceutical companies to expand further into this area expose a vast untapped potential this industry is yet to reach. Roughly there are about 6 ,500- 8,000 rare diseases in India which include Norrie Disease, Wilson Disease, and Arthrogryposis.

The effect of this will be two-pronged- one on manufacturers and the other on the patients themselves. For manufacturers, the market for these drugs may appear small, but this is more than counterbalanced by the revenue opportunities and the quick time-to-market. For patients, the burden of cost will fall entirely on them in the short run which can be avoided in the future with the help of state run incentives for manufacturers. This will allow manufacturers to produce drugs that focus on common medicines and orphan drugs alike and decimate the established system of our health care system is funded almost solely by patients.
Another systemic problem that will be solved when manufacturing processes are moved to home base is one that arises from the transportation and movement of goods. Importers have taken up the option of using carriers or gray market routes which put patients' lives at risk. This is truer for drugs that have a biological or bio-similar root because external factors such as the proper temperature, storage, and transport of these drugs severely impact the efficacy. As per industry norms and standards, the drugs must be stored between 2-8º C. If not, the stability of drug could hamper the efficacy and will not deliver the desired results causing it to be the public hazard. Varying temperature, improper storage units, and inappropriate transportation methodology often have fatal consequences on the recipient of these drugs.

Earlier, there were no formal incentives from the government that focuses on developing affordable drugs for common diseases such as oral insulin for preventing or slowing the progression of cardiovascular disease and vaccines and antibiotics for some preventable infectious diseases. Hence, patients with rare diseases rely on imported drugs from other countries which makes it unaffordable for the common man even if they are available. Organization for Rare Diseases in India (ORDI) intends to work between the Government of India and the Pharma/Biotech/Diagnostic industry to establish an Orphan Drugs Act (ODA) that will generate incentives for orphan drug developers.

Even though the government has attempted to steps to provide some respite from the complicated import procedures, they must take a step towards not only simplifying the import of life-saving drugs by reducing the number of procedures; but also place heavy embargos on the illegal smuggling of high -value drugs. The rules must be changed to suit the patient in need and not the manufacturers who can wield a price controlled power over these medicines.

The issue of illegal smuggling can be curbed by initiating a "Qualification process" for authorized importers by publishing a list of them in a public domain. This would not be a difficult endeavor as over 75% of pharmaceutical companies are already in the organized sector. Companies will be required to rethink their business models just as governments are restructuring their regulatory intervention. This intervention will ensure that the processes of trading in drugs that are vital to human life in all countries are made simpler.

These acts and regulations in India will not only raise the burden off of the patients but will open the doors to the true potential of the pharmaceutical landscape in our country by giving affordable and accessible drugs to those in need. The health of our population is an important aspect of improving the overall Human Development Index of our country that is currently abysmally low.

WHO-GDP Certification

consume it because of the lack of proper conditions in which they are moved from one place to another. Counterfeit pharmaceutical products are also a real threat to public health and safety. Consequently, it is essential to protect the pharmaceutical supply chain against the penetration of such products.

In order to curb this, a proper system must not just be established but also implemented. The WHO has set up an international protocol called the WHO- Good Distribution Practices (GDP). Good distribution practice (GDP) deals with the guidelines for the proper distribution of medicinal products for human use. GDP is a quality warranty system, which means that procurement, purchasing, storage, distribution, transportation, repackaging, relabeling, documentation and record-keeping practices are met after stringent audits and protocols.

Internationally accepted pharmaceutical GDP regulations stipulate that distributors of pharmaceutical products must align their operations with the standards. The scheme ensures that consistent quality management systems are in place throughout the entire supply chain, from the early delivery of raw materials to the manufacturing plants, the final shipment of finished drugs to the end user. An independent assessment of compliance with international GDP requirements is the most effective way to establish that a quality management system aligns with GDP guidance. Right from the manufacturer to the doctor's office, GDP supply chain or parameters are to be maintained.

Various persons and entities are often responsible for the handling, In some cases, however, a person or entity involved in the distribution of pharmaceutical products is only involved and is responsible for certain elements of the distribution process. The guidelines are intended to apply to all steps in the entire distribution/supply chain. The relevant sections should be considered by various role players as applicable to their particular role in the distribution process. The storage, trade, and distribution of pharmaceutical products are activities that are carried out by various companies, institutions and individuals. The nature of the risks involved may generally, however, be the same as those in the manufacturing environment, e.g. mix-ups, contamination, and cross-contamination.

There are aspects of distribution to which the principles of Good Manufacturing Practice (GMP) should be applied. These include, but are not limited to, storage, distribution, transportation, packaging, labeling, documentation, and record keeping practices. In order to maintain the original quality, every activity in the distribution of pharmaceutical products should be carried out according to the principles of GMP, Good Storage Practice (GSP) and Good Distribution Practice (GDP). If these processes are followed and the protocols are kept in check, there is no doubt that people who are in dire need of medication anywhere in the world will not only receive the drugs on time but also at an affordable cost with the correct efficacy and a value for their money. This will ensure that no person faces a fatal consequence for the lack of medical aid or because of complex trade regimes and will put a complete stop to the illegal smuggling of pharmaceutical products across country borders.