Cipla to invest in South Africa’s first biosimilars production facility
Indian-based pharmaceutical and biotechnology company Cipla will invest more than R1.3bn ($19.34m) in the first advanced biotech manufacturing facility in South Africa for the production of biosimilars.

Indian-based pharmaceutical and biotechnology company Cipla will invest more than R1.3bn ($19.34m) in the first advanced biotech manufacturing facility in South Africa for the production of biosimilars.

The investment will be carried out by South African subsidiary Cipla BioTec…………………cont

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http://www.pharmaceutical-technology.com/news/newscipla-invest-south-africas-first-biosimilars-production-facility-4945516?WT.mc_id=DN_News

Cipla Managing director and global CEO Subhanu Saxena

Dr Y.K. Hamied,

Department of Trade and Industries Special Economic Zone of Dube Tradeport, DURBAN, SOUTHAFRICA

///Cipla, South Africa, biosimilars, production facility, Dube Tradeport, Cipla BioTec Pvt Ltd, Durban, SOUTHAFRICA

The Water Purification Process

Water purification is the process of removing undesirable chemicals, biological contaminants, suspended solids and gases from contaminated water. The goal is to produce water fit for a specific purpose. Most water is disinfected for human consumption (drinking water), but water purification may also be designed for a variety of other purposes, including fulfilling the requirements of medical, pharmacological, chemical and industrial applications. The methods used include physical processes such as filtration, sedimentation, anddistillation; biological processes such as slow sand filters or biologically active carbon; chemical processes such as flocculation andchlorination and the use of electromagnetic radiation such as ultraviolet light.

Purifying water may reduce the concentration of particulate matter including suspended particles, parasites, bacteria, algae, viruses, fungi, as well as reducing the amount of a range of dissolved and particulate material derived from the surfaces that come from runoff due torain.

The standards for drinking water quality are typically set by governments or by international standards. These standards usually include minimum and maximum concentrations of contaminants, depending on the intended purpose of water use.

Visual inspection cannot determine if water is of appropriate quality. Simple procedures such as boiling or the use of a household activated carbon filter are not sufficient for treating all the possible contaminants that may be present in water from an unknown source. Even natural spring water – considered safe for all practical purposes in the 19th century – must now be tested before determining the kind of treatment, if any, is needed. Chemical and microbiological analysis, while expensive, are the only way to obtain the information necessary for deciding on the appropriate method of purification.

According to a 2007 World Health Organization (WHO) report, 1.1 billion people lack access to an improved drinking water supply, 88 percent of the 4 billion annual cases ofdiarrheal disease are attributed to unsafe water and inadequate sanitation and hygiene, while 1.8 million people die from diarrheal diseases each year. The WHO estimates that 94 percent of these diarrheal cases are preventable through modifications to the environment, including access to safe water.^[1] Simple techniques for treating water at home, such as chlorination, filters, and solar disinfection, and storing it in safe containers could save a huge number of lives each year.^[2] Reducing deaths from waterborne diseases is a major public health goal in developing countries.

Water purity is extremely important to pharmaceutical and biochemical industries. Suspended or dissolved particles, organic compounds, impurities and other contaminants prohibit the usage of tap water in laboratory applications and scientific research. Parameters such as resistivity, conductivity, size of particulate matter and concentration of microorganisms are used to categorize water quality and, therefore, specify intended uses for water. Some applications can tolerate the presence of specific impurities in the water, but others, such as High Performance Liquid Chromatography (HPLC) require removal of the majority of contaminants.

Contaminants

Water is an excellent solvent and can be sourced from almost anywhere on Earth. This property makes it prone to all kinds of contamination.

Particulates: Silt and debris which can be removed by passing water through a 10 to 20 micron filter (or less if necessary).
Microorganisms: Bacterial agents constitute a real challenge for water purification systems. Their growth rate, size and robustness require an efficient design (detection, removal from water inlet, inhibition of growth, etc.). Bacteria are measured in colony forming units per milliliter and can be killed with disinfectants. As a result, their secretions and cellular fragments must also be removed to avoid contamination.
Endotoxins, pyrogens, DNA and RNA: Cellular fragments and bacterial by-products. Harmful to tissue cultures. Can be detected with a Limus Amoebocyte Lysate (LAL) test.
Dissolved inorganic elements: Include phosphates, nitrates, calcium and magnesium, carbon dioxide, silicates, iron, chloride, fluoride, and any other natural or man-made chemicals resulting from exposure to the environment. Electrical conductivity (μSiemens/cm) is used to monitor high concentration of ions, while resistivity (MÙcm) is used to identify ions if present in small concentrations. These contaminants affect water hardness and alkalinity/acidity.
Dissolved organic elements: Pesticides, plant and animal remains or fragments. Total Organic Carbon (TOC) analyzers are used to measure CO2 emitted by organics subjected to oxidization. Organic-free water is mainly used in applications where analysis of organic substances is carried out (e.g. HPLC, chromatography and mass spectrometry).

Scientific applications require elimination of certain types of contaminants. On the other hand, pharmaceutical productions require, in most cases, near-total removal of impurities (criteria dictated by specific standards or local/international regulatory bodies).

Purification Process

There are a number of methods commonly used to purify water. Their effectiveness is linked to the type of contaminant being treated and the type of application the water will be used for.

Filtration: This process can take the form of any of the following:
- Coarse filtration: Also called particle filtration, it can utilize anything from a 1 mm sand filter, to a 1 micron cartridge filter.
- Micro filtration: Uses 1 to 0.1 micron devices to filter out bacteria. A typical implementation of this technique can be found in the brewing process.
- Ultra filtration: Removes pyrogens, endotoxins, DNA and RNA fragments.
- Reverse osmosis: Often referred to as RO, reverse osmosis is the most refined degree of liquid filtration. Instead of a filter, it uses a porous material acting as a unidirectional sieve that can separate molecular-sized particles.

Distillation: Oldest method of purification. Inexpensive but cannot be used for an on-demand process. Water must be distilled and then stored for later use, making it again prone to contamination if not stored properly.
Activated carbon adsorption: Operates like a magnet on chlorine and organic compounds.
Ultraviolet radiation: At a certain wavelength, this might cause bacteria to be sterilized and other micro organics to be broken down.
Deionization: Also known as ion exchange, it is used for producing purified water on-demand, by passing water through resin beds. Negatively charged (cationic) resin removes positive ions, while positively charged one (anionic) removes negative ions. Continuous monitoring and maintenance of the cartridges can produce the purest water.

Hot Water Sanitization

Sanitization of water purification equipment with hot water is achieved via an appropriate combination of exposure time and temperature. A primary use for this process is to deactivate viable microbes. It is worth mentioning that Endotoxin reduction is not achieved as a direct result of the hot water sanitization process.
Based on the feed water source, system operating conditions and the end-user’s operating and maintenance procedures, traditional chemical cleaning processes may still be required.
Sanitization using hot water involves incorporating heat exchangers into the traditional clean in place (CIP) system to gradually heat and cool water circulating through the reverse osmosis membrane system. Membrane manufacturers commonly stipulate a controlled heating and cooling rate to protect against irreversible damage to the membrane and ensure the system’s long-term performance.
A typical hot water sanitization sequence would consist of the following phases:

Initialization (conditions checking)
Heating
Holding
Cooling

A control system must therefore provide flexibility in the way in which accurate and repeatable control of the sterilization is achieved and will

include the following features:

Precise loop control with setpoint profile programming
Sequential control for sanitation/sterilization
Onscreen operator messaging
Duty standby pump control
Secure collection of on-line data from the purified water system for analysis and evidence
Local operator display with clear graphics and controlled access to parameters

Control room and schematics of the water purification plant to Lac de Bret, Switzerland

Bottle for distilled water in theFarmacia Real in Madrid

Large cation/anion ion exchangersused in demineralization of boiler feedwater

Pharmaceuticals can enter the water supply in a variety of ways. Debates continue over how dangerous this is. Source: GAO

Information sheet: Pharmaceuticals in drinking-water

(This information sheet is a summary of the key findings, recommendations and conclusions of the WHO technical report on Pharmaceuticals in drinking-water and the inputs of additional expert peer-reviewers)

Background and scope

Pharmaceuticals are synthetic or natural chemicals that can be found in prescription medicines, over-the-counter therapeutic drugs and veterinary drugs. Pharmaceuticals contain active ingredients that have been designed to have pharmacological effects and confer significant benefits to society. Pharmaceuticals can be introduced into water sources through sewage, which carries the excreta of individuals and patients who have used these chemicals, from uncontrolled drug disposal (e.g. discarding drugs into toilets) and from agricultural runoff comprising livestock manure. They have become chemicals of emerging concern to the public because of their potential to reach drinking-water.

Occurrence of pharmaceuticals in drinking-water

The ubiquitous use of pharmaceuticals (both prescribed and over the counter) has resulted in a relatively continuous discharge of pharmaceuticals and their metabolites into wastewater. In addition, pharmaceuticals may be released into water sources in the effluents from poorly controlled manufacturing or production facilities, primarily those associated with generic medicines.

Following advances in the sensitivity of analytical methods for the measurement of these chemicals at very low concentrations, a number of studies found trace concentrations of pharmaceuticals in wastewater, various water sources and some drinking-waters. Concentrations in surface waters, groundwater and partially treated water were typically less than 0.1 µg/l (or 100 ng/l), whereas concentrations in treated water were generally below 0.05 µg/l (or 50 ng/l). These investigations suggested that pharmaceuticals are present, albeit at trace concentrations, in many water sources receiving wastewater effluents.

The presence of specific pharmaceuticals in a water source will vary from place to place depending upon the type of pharmaceutical and the extent of discharge into water bodies. Key factors include the pharmaceuticals prescribed, used or manufactured in the area and the size of the population in the catchment. The occurrence and concentration of pharmaceuticals in receiving water sources, which are the primary pathway into drinking-water, are dependent on dilution, natural attenuation and the degree of wastewater treatment applied.

Risk assessment of pharmaceuticals in drinking-water

There are currently few systematic monitoring programmes or comprehensive studies available on human exposure to pharmaceuticals from drinking-water. Therefore, a key challenge in assessing the potential human health risk associated with exposure to very low concentrations of pharmaceuticals in drinking-water is the limited occurrence data available for the diverse group of pharmaceuticals in use today and their active metabolites.

However, several approaches for screening and prioritizing pharmaceuticals for human health risk assessment for exposure through drinking-water have been published in the peer-reviewed literature. These approaches usually apply the principle of the “minimum therapeutic dose” (also known as the “lowest clinically effective dose”) or the acceptable daily intake, in conjunction with safety factors or uncertainty factors for different groups of pharmaceuticals, to derive a margin of safety, or margin of exposure, between the worst-case exposure observed or predicted and the minimum therapeutic dose or acceptable daily intake.

Current observations suggest that it is very unlikely that exposure to very low levels of pharmaceuticals in drinking-water would result in appreciable adverse risks to human health, as concentrations of pharmaceuticals detected in drinking-water (typically in the nanogram per litre range) are several orders of magnitude (typically more, and often much more, than 1000-fold) lower than the minimum therapeutic dose.

Control measures and risk management

Concentrations of the vast majority of pharmaceuticals in the water environment can be reduced through natural processes (e.g. adsorption onto sediment, solar photodegradation and biological degradation) or during subsequent drinking-water and wastewater treatment processes.

Despite their unique pharmacological properties, pharmaceuticals respond to treatment no differently from other organic chemicals, with removal rates depending on their physicochemical properties and the treatment technology being used. Conventional water treatment processes, such as chlorination, can remove approximately 50% of these compounds, whereas more advanced treatment processes, such as ozonation, advanced oxidation, activated carbon, nanofiltration and reverse osmosis, can achieve higher removal rates; reverse osmosis, for example, can remove more than 99% of large pharmaceutical molecules.

Funding for any water safety improvements, like any public health intervention, draws on limited resources that need to be carefully allocated with due consideration of their beneficial impact. However, implementing additional specialized and costly drinking-water treatment, specifically with the intention of reducing trace concentrations of pharmaceuticals, is not considered necessary at this time, as the human health benefit would be limited.

The most appropriate approach to minimize the presence of pharmaceuticals in drinking-water and reduce human exposure is to prevent or reduce their entry into the water environment as far as reasonably practical. This can be achieved through a combination of preventive measures, including enhanced communication to the public on rational drug use and disposal of pharmaceuticals (e.g. avoid flushing unused drugs down the toilet), education for prescribers and systematic drug take-back programmes.

However, in line with the water safety plan principle of control of contaminants at the source, it would be appropriate to investigate improvements in wastewater treatment to remove pharmaceuticals and other potential contaminants of concern from their main route of entry into the water environment.

Monitoring of pharmaceuticals in water

In the absence of regulatory mandates, routine monitoring for pharmaceuticals in water sources and drinking-water on a national basis would not be desirable except in cases where local circumstances indicate a potential for elevated concentrations (e.g. manufacturing facilities with uncontrolled effluent discharge upstream of a drinking-water source). In these circumstances, investigative monitoring of, for example, surface water, groundwater and wastewater effluent can be undertaken to assess possible occurrence levels and exposure; if necessary, screening values can be developed in conjunction with an assessment of the potential risks to human health from exposure through drinking-water.

Based on the results of this risk assessment, an evaluation of possible control options could be considered as part of a water safety plan. Practical difficulties associated with implementing monitoring programmes for pharmaceuticals include the lack of standardized sampling and analysis protocols, high costs and the limited availability of the analytical instruments required to measure the diverse range of pharmaceuticals that may be present.

Investigative surveys should be tailored to local circumstances, taking into account existing wastewater and water treatment processes and pharmaceuticals (and their metabolites) that are commonly prescribed, used or manufactured within the catchment area of concern. Such studies should be carried out with appropriate rigorous quality assurance and verification and designed to confirm whether drinking-water is a significant risk.

Knowledge gaps

Although current risk assessments indicate that the very low concentrations of pharmaceuticals found in drinking-water are very unlikely to pose any appreciable risks to human health, knowledge gaps exist. These include the assessment of risks to human health associated with long-term exposure to low concentrations of pharmaceuticals and the possible combined effects of mixtures of pharmaceuticals.

Although the margins of exposure are substantial, it would be of value to ensure that these margins are adequate for possibly sensitive subpopulations and to better characterize health risks, if any, from long-term, low-level exposures. In addition, future research should focus on developing methods or protocols for prioritizing pharmaceuticals in the context of an overall risk assessment for all drinking-water hazards.

Summary

Currently, analysis of the available data indicates that there is a substantial margin of safety between the very low concentrations of pharmaceuticals that would be consumed in drinking-water and the minimum therapeutic doses, which suggests a very low risk to human health. Based on this finding, the development of formal health-based guideline values for pharmaceuticals in the World Health Organization’s (WHO) Guidelines for drinking-water quality is currently not considered to be necessary.

Concerns over pharmaceuticals in drinking-water should not divert water suppliers and regulators from other priorities for drinking-water and health, most notably microbial risks, such as bacterial, viral and protozoan pathogens, and other chemical risks, such as naturally occurring arsenic and excessive levels of fluoride.

SOUTH AFRICAN CUISINE