Be it while prescribing a medicine, or you looking at the constituents of the drug purchased, we always think of the active pharmaceutical ingredient (API). No one looks at the list of excipients, as these are considered to be "inert" rather than "active". In our mindset, these are mere fillers that allow the finished formulation to be formed and carried within the patient's body.

No doubt, the drug products give life to us due to active ingredients present, the excipients are the ones who aid that product for efficient delivery to particular site of action. These excipients typically make up about 99 per cent of a finished drug product, and are derived from various sources (natural, biological and chemical etc) and can be targeted for use in a variety of products intended for very diverse businesses (food, general industrial, cosmetics and pharmaceutical, etc.). Their role in pharmaceutical products can vary from non-critical to highly sophisticated/functional, depending on the drug and dosage form/design (for example control rate of delivery, flavouring, stabiliser, emulsifier and colourant etc.).

Although listed as inactive ingredients by FDA, excipients generally have well-defined functions in a drug product. The excipients may be small molecule or complex and may vary in terms of degree of characterization. They may be chemically synthesized or may be either natural source or biotechnology-derived (recombinant). In contrast to active ingredients, minor components of an excipient may have significant impact on its pharmaceutical performance. One interesting fact is that an excipient in a drug product may be an active ingredient in another formulation, depending on its intended use.

A huge number of serious ADRs are caused by excipients. Geiling and Cannon reported 76 deaths from acidosis and renal failure following the use of elixir of sulfanilamide; for this, the excipient diethylene glycol was found to be the cause. There were later reports of more than 100 deaths. The toxic nature of diethylene glycol was noticed again some 50 years later by Cantarell and collaborators. They described oliguria and acidosis in patients with burns who were treated with topical antibacterials containing diethylene glycol.

Even today, the excipients have not been a major source of concern. There are instances where identified issues may have been minimised or eliminated using better control of the essential elements of GMPs: traceability, change control/customer notification, contamination control. If we look at the history, around 100 deaths resulted from cough syrup (distributed to children in Haiti between 1995 and 1996) that was contaminated with diethylene glycol, according to the World Health Organization (WHO).

In 1999, some poultry, swine and ruminants (cattle, sheep and goats) were fed food contaminated with dioxins and poly chlorinateddd biphenyls (PCBs), thus contaminating the animals with both dioxins and PCBs. As a result, it became important for manufacturers using materials from animal origins to verify the source (traceability) of their raw materials to ensure that they are not contaminated.

Now - a -days, risk assessment or risk management is the basis for defining the appropriate level of GMPs. For using these tools, a complete understanding of the end-use applications (for example dosage forms, drug types and delivery mechanisms etc) is required. The excipients industry neither have access to this information, nor does the pharmaceutical industry provide this type of information to their raw material providers. This will require a lot of collaboration and investment from both parties, especially when distributors and brokers are also involved.

The primary focus of risk assessment for the use of excipients in any drug product is patient safety. Don’t think that only active ingredients are related to risks, even excipients can take part. Risk assessment requires a permanent examination of the excipient's and manufacturer's risk profile, based on the following five observation criteria:

• Number of quality defects in excipient batches  
• Type and severity of the defects  
• Loss of accreditation at the excipient manufacturer  
• Trends at the quality attributes of the medicinal product (depending on nature and role of the excipient in the dosage form)  
• Audit at the excipient manufacturer

Key players in excipient market
We can understand the diverse functional aspects and importance of excipients, but still they have been overlooked in the presence of active ingredients of the drug formulation in the pharmaceutical industry. Currently, with the change in the status of non- active additives to active ingredients, a large number of players have come forward to provide highly competent and best quality excipients to the various pharmaceutical firms across the globe.

Few well established names in the pharma industry includes Gattefosse and BASF, known for their wide array of surfactants such as Tweens; Roquette for its cyclodextrins- injectable grade; DMV-Fontera is known worldwide for its non pyrogenic excipients while AVANTI Polar and LIPOID are the leaders in providing Phospholipids such as DSPC, HSPC and many others.

These excipient manufacturers are considered as the leaders in India because as such there is no leading player of Indian origin across the globe at present. Thus, these players are generating good profits by catering to the requirements of the various pharmaceutical companies of India through their wide range of high quality excipients.

Current scenario in India and across the globe
Tremendous rise is seen in the utilization of high quality excipients, which makes a part of drug innovations. This has accomplished in increased demand globally for excipients thereby resulting in the growth of these 'once inactive ingredients'. Also, the rapidly growing pharmaceutical market in India, multiplying demands for novel formulations, accessibility and availability of highly sophisticated technology and the development of new drug delivery systems are further promoting the development of the excipient industry in India.

Apart from this, several generic drugs are slated to go off patent in the near future, thus offering enormous opportunity to the Indian excipient industry to go in response and reap the benefits. Keeping in mind these growth potential of excipients, a number of foreign players have plans to enter Indian market through FDI route for setting up their manufacturing plants here.

Additionally, India also offers low cost manufacturing capabilities along with quality assurance are certainly opening doors for the foreign players to make profitable grounds in India. India being a hub for pharma drug development and technology advancement, Indian excipient market is expected to grow tremendously, thus catering not only to needs of the locals but also the various countries around the globe. As per the statistics, India and China are catering to 1/3rd of the excipients demands by importing it from the foreign players. Also, India has become a highly active in exporting of finished formulations in the regulated markets of the world.

Road blocks in excipient market
The excipient belt of the pharmaceutical industry has become sustainable and steady over time due to the rising recognition of the importance of standard and good quality excipients usage.

Over the years, pharma industry has realized that the usage of low standard excipients obstruct the proper functioning of the active ingredient thereby negating the primary purpose of the drug formulation.

Due to this increasing awareness in the market in India and across the globe, the unorganised sector of excipient manufacturing industry has lost its flavour and trust. Certain other challenges that the industry has faced and is still facing includes:

High price
As such India does not have any excipient manufacturer of its own, therefore procuring excipients in large quantity from the foreign market is an expensive task and is not economical for a new entrant in the industry. For e.g. Pegylated phospholipids, cholesterol, highly purified surfactant are highly expensive excipients, the usage of which automatically increase the cost of the formulation. Therefore, it becomes a great challenge to avail cost-effective and quality excipients for multi-functional use at reasonable rates.

Lack of adequate regulatory approvals
As India is a new player in the excipient industry with no manufacturer of its own and has very limited excipients listed in its Pharmacopoeia. Also, the nation also lacks adequate regulatory measurements for the same, which may lead to the usage of contaminated excipients in drug manufacturing thus causing adverse effects. Therefore, the government should take strict actions in keeping a regulatory check on the excipients, thereby help the pharmaceutical industry of India to flourish magnificently.

Absence of strict guidelines
Today, the Indian excipients industry need stringent guidelines, certain technical and pharmacological experts in fore to ensure the proper approval of animal toxicological studies regarding the excipients made from animal source. Local sensitivity and irritability studies must be conducted along with the certifications such as BSE/ TSE, HIV free, Hepatitis free and so on before selling off the excipients made from animal source such as gelatin, human serum etc.

Future outlook
Despite these wobbling blocks, the excipient industry is poised to grow tremendously in the near future. Let us thanks to the sustained economic growth, healthcare reforms and patent-related legislation of India, which is drawing the interest of the pharmaceutical giants around the globe to start their ventures here. Apart from these, doubling of disposable incomes and the number of middle-class households, expansion of medical infrastructure, greater penetration of health insurance, rising prevalence of chronic diseases, adoption of product patents and aggressive market penetration driven by the relatively smaller companies are other proven stepping stones in the growth of the Indian pharmaceutical Industry. All said and done, the path of globalization is full of opportunities but simultaneously fraught with risks as well, as it calls for tremendous change in the mindset and transformation to attract global capital and talent.