The Indian pharma market is the world’s third-largest in terms of volume and 13-largest in terms of value. India has the highest number of US-FDA approved plants outside the US. The domestic pharmaceutical market turnover reached `129,015 crore in 2018, and pharmaceutical exports stood at US$17.27 billion in the same year. India supplies over 50% of the global demand for vaccines, 40% of the demand for generic drugs in the US, and 25% of all medicine in the UK. Indian drugs are exported to more than 200 countries in the world, with the US as the key market. Generic drugs account for 20 per cent of global exports in terms of volume, making India the largest provider of generic medicines globally. The growth of the pharma industry in India consequently increases the need for better technology and cleaning methods to maintain stringent standards of pharmaceutical production. Mrigank Warrier explores the growth of the pharma industry vis-à-vis the cleaning market.
In India, pharma manufacturing clusters are located in Maharashtra (Mumbai-Pune and Aurangabad), Gujarat (Ahmedabad-Vadodara), Delhi-UP, Haryana, Madhya Pradesh (Indore) Uttarakhand (Dehradun), Andhra Pradesh (Hyderabad-Medak), and Odisha (Cuttack- Bhubaneswar). Over the last five years, the pharma sector has been growing at a compounded annual growth rate (CAGR) of more than 15%.
Projected Future Growth.
It is estimated that by 2020, the prevalence of chronic or long-term diseases such as diabetes and cancer will increase by 25-40%. These will require ramped-up manufacturing of drugs which can manage them over months and years. Corporate hospital chains will expand their hospital network in the top 70 cities; hub-and-spoke delivery models providing access to higher levels of care will rise within the top 200-250 towns. More and more people will be able to access quality hospitals, which will drive the need for medication.
Rising incomes will drive 73 million households into the middle- and upper-income segments, expanding the market of those who can afford to spend on medicines. Increased health insurance coverage will augment affordability. By 2020, nearly 650 million people will enjoy health insurance coverage. Private insurance coverage will grow by nearly 15 per cent annually till 2020. However, the largest impact will be seen through government sponsored programmes that are largely focused on the ‘below poverty line’ (BPL) segment, and are expected to provide coverage to nearly 380 million people by 2020. At the moment, the Ayushman Bharat mission provides 100 million poor families in the country with a cover of up to `5 lakh per belowpoverty- line family per year for secondary and tertiary care hospitalisation. Since all this will reduce out-ofpocket expenses, medicines will be more frequently and regularly bought.
At present, four of the top ten players in the pharma industry, including the market leader, are new entrants. The Drug Controller General of India (DCGI) has announced its plans to start a single-window facility to provide approvals for setting up pharma manufacturing centres, which will further encourage the entry of new ventures. It should come as no surprise that the industry is set to grow to $50 billion by 2020, and likely to be in the top 10 global markets in terms of value.
Now that we know the immense potential of this sector, we must not forget that few other sectors place the same importance of cleanliness and hygiene as the pharma sector. By law, they are required to do so; as businesses, it is in their own best interests to ensure that their products – which are consumed by sick people — do not cause sickness themselves. Over the years, the rigour of cleanliness regimens in manufacturing plants has become increasingly stringent.
The core parts of a pharma manufacturing plant are the rooms in which different steps of the process like granulation, blending, capsule filling, syrup filling, tablet compression, coating and packing are done. Since much of the process is automated and most involve some kind of device, a whole range of machines and equipment like mixing tanks, tablet presses, capsule fillers, centrifuges, granulators, filling lines, mixers, conveyors, filters, fluid lines, batch process tanks, tubes and flasks all need to be thoroughly cleaned.
What do they need to be cleaned of?
• Soils: Traces of the various ingredients used in production or soils from the actual manufacturing process such as oil, grease, dust or minerals. Understanding the soils that are present guide the choice of cleaning detergent.
• Excipients: Colours, flavours and other excipients and decomposition materials from excipients.
• Micro-organisms: Bacteria such as Staphylococcus aureus and E. coli.
• Particulate contamination: Presence of specks and fibre.
• Residue of detergents used for cleaning purpose.
• Residual Rinse Water: In instances where even a trace amount of moisture could be detrimental to product quality, the cleaning procedure must leave the equipment free of any trace of the final rinse solution.
Gels, polyethylene glycol, oils, titanium dioxide, dyes, silicons, flavourings, petrolatum, paraffin, proteins, steroids, sugars, alcohol, stearates, and corn-starch are some of the typical pollutants that are often found on pharmaceutical processing equipment. Ideally, none of these should become part of a drug formulation, beyond certain acceptable limits.
Equipment and production areas are cleaned by variety of techniques, depending upon the type of impurity:
1. Mechanical action: brushing, scrubbing, pressurized water to remove particulates.
2. Dissolution: dissolving various kinds of residues left on pharma processing equipment with a suitable solvent.
4. Chemical reactions such as oxidation and hydrolysis in which the residues are chemically changed.
Cationic (positively charged) detergents tend to leave persistent residues which adhere very strongly to glass and are difficult to remove. Since this can affect the drug formulation and it stability, it should be avoided.
Non-ionic (neutrally charged) detergents are preferred. They do not ionise when dissolved in water. Since the detergent is made of both acidic and alkaline components, it remains at a neutral pH when dissolved in water. They typically produce less foam when mixed with water as compared to ionic detergents, and are easier to wash away from the equipment being cleaned, leaving lesser residue behind than ionic detergents, thereby reducing the chance of any contamination and preventing any interference with analysis. They are well suited for removing oil from surfaces.
Oil spills are cleared with 70% IPA, also used to wipe glass panes. Non-detergent chemical cleaning is done using sodium hypochlorite or hydrogen peroxide. Alkaline cleaners are the best choice for cleaning soils such as gels, dyes and petrolatum. Citric acid-based cleaners are better suited for removing titanium dioxide. Protein or starch-based soils may require the use of an enzyme cleaner.
In the general area, chemicals like sodium benzene sulphonate, alcohol ether sulphate and alcohol ethoxylate can be used. In sterile areas such as ampoule-filling and other injectables processing rooms, sterilisation is mandatory; cresol, Chlorhexidine Gluconate, Cetrimide, Isopropyl alcohol can be used.
Cotton mops are avoided in the pharma industry, as they may leave cotton fibres behind, which may enter processing equipment. Nylon brooms are preferred. In the tablet manufacturing area, wet floor mops are used. Vacuum cleaners are used to absorb dust generated on the external surface of machines in the tablet compression area. In sterile production areas, sterile, lint-free mops are compulsory; even the disinfectant is diluted in sterile distilled water. Scrubber-cum-driers are used in the non-sterile areas. When major cleaning is undertaken, pipe brushes and are used to clean the grilles of Air Handling Units.