Bio-drugs a Blessing but Need Regulation

As a new generation of bio-pharmaceutical drugs undergoes trials in India, experts are asking if there is regulation enough to protect patients should something go wrong. The question is urgent. Bio-pharmaceutical drugs are made using living systems such as micro-organisms, plants or animal cells. If unwittingly altered while being manufactured or administered, they can cause coronary heart disease, cancer and infertility.

Bio-pharmaceuticals, which are very different from synthetic drugs that are made out of simple, well-defined chemical compounds, are increasingly being used to treat cancer, multiple sclerosis and kidney failure.

But India's Drugs and Cosmetics Rules (DCR) don't differentiate between chemical and bio-pharmaceutical drugs, says C M Gulhati, editor, Monthly Index of Medical Specialties (MIMS). If something went wrong with a bio-pharmaceutical, there would be little succour to be had from regulations.

Gulhati says it is not idle speculation. Two years ago, the US Food and Drug Administration (FDA) blacklisted and barred the import and sale of 31 synthetic medicines manufactured by Ranbaxy Laboratories at its Paonta Sahib and Dewas factories in India. FDA inspectors had detected "multiple, serious deficiencies" in the manufacturing processes in violation of 'good manufacturing practices.' Gulhati says that part of the problem is the smaller trials now required before new drugs are accepted for general use. "Earlier, up to January 2005, Phase III (advanced) trials needed a minimum of 100 subjects in three to four centres. Now, this minimum has been removed on 'friendly persuasion' and 'advice' from drug companies, putting patients at risk."

Add to that the trend for pharmaceutical companies to outsource clinical trials to clinical research organizations that may not be accredited. "It is time India had a National Biotech Association of India to control all bio-products," says Dr Ranjit Roy Chaudhury, national professor of pharmacology, National Academy of Medical Sciences.

The Drugs and Cosmetics Rules require inspectors to visit every drug manufacturing plant at least once a year. But that doesn't happen, says Gulhati. By 2016, many bio-pharmaceuticals will come off patent worldwide and India, Brazil and China sense a huge opportunity to manufacture and sell bio-similars, which reportedly have similar properties. In India alone, this market is estimated to touch $580 million by 2012.

Bio-similars would make health care more affordable because they cost one-third of bio-pharmaceuticals but manufacturing procedures have to be stringent. "Their safety and efficacy is highly dependent on the robustness and monitoring of quality aspects as even minor changes can affect the body," says Dr Anoop Misra, head of the department of diabetes and metabolic diseases, Fortis Hospitals. "Due to certain laxities, it's easier for bio-similars to get into the Indian market than abroad."

M K Bhan, secretary, department of biotechnology, assures that the Biotech Regulation Authority Bill would come out with guidelines within a few months. "We are working with the Drug Controller of India for a one-window regime for drug companies." Misra says that some erythropoietins, a bio-similar that controls red blood cell production, have caused health problems abroad. Almost 500 patients given the bio-similar during trials in 1998-2003 reportedly developed life-threatening anaemia.

Doctors say bio-similar trials should have several hundred patients, preferably grouped at one centre in order to study patients with similar adverse reactions. But pharmas do them in many centres with small groups, alleges Gulhati.

"In India, regulation for bio-similars is weak, when it should be more stringent than synthetic drugs," says Chaudhury. "Synthetic drugs need a bio-availability study, whereas bio-similars need many more for toxicity, immunology etc, to ensure consistency, quality and purity."

Visiting Indian pharmaceutical firms seek local partners

Seventeen Indian pharmaceutical enterprises yesterday met with HCM City partners during a trade-exchange programme to seek more opportunities in the field.

The companies produce a wide range of pharmaceutical goods, including functional food and veterinary medicine.

Pharmaceuticals are one of the major products that India exports to Viet Nam.

Two-way trade between the two countries was more than US$2 billion in 2009, with an annual growth of 20 per cent.

From 2008-10, the Vietnamese pharmaceutical industry increased turnover by 12 per cent annually.

Last year, the industry sold around $700 million of drugs on the local market. The rest, which amounted to 50 per cent of sales, was imported medicine.

Viet Nam also exported $40 million worth of drugs last year, an increase of 20 per cent compared to 2008.

However, the local pharmaceutical industry is expected to continue to produce only basic medicines, and will not manufacture specialised drugs for heart or cancer diseases.

Most of the raw materials are imported from China (25 per cent) and India (21 per cent).

Last year, Viet Nam spent $1.17 billion on imported medicines.

Demand for medicine per capita increased from $6 in 2001 to $16.5 in 2008, and is expected to reach to $25 in 2015. — VNS

Salesforce.com and Veeva Systems Announce Expanded Alliance to Serve the Global Pharmaceutical and Biotechnology Industry

Veeva Systems and salesforce.com the enterprise cloud computing company, today announced an expanded alliance to accelerate the delivery of the market-leading Veeva CRM applications to the global pharmaceutical and biotechnology industry. Utilizing Force.com, salesforce.com's enterprise cloud computing platform, Veeva has quickly become a market leader for Pharma CRM. Industry leaders, including three of the world's largest five pharmaceutical companies, have selected Veeva CRM running on Force.com to power their commercial operations.

Jazz Tobaccowalla, SVP of Worldwide Biopharmaceutical Businesses, Business Technology, Pfizer stated, "I am excited to see the expanded partnership between Veeva and salesforce.com. Together they are bringing enterprise cloud computing to our industry."

"Building on top of Force.com provides Veeva a leg up on our competition in the Pharma CRM market," explained Peter Gassner, CEO of Veeva Systems. "Veeva is now salesforce.com's premier Independent Software Vendor (ISV) partner for sales force automation in the pharmaceutical and biotechnology segment. This expanded partnership will further fuel our success."

"Veeva's success is a clear demonstration of ISV success with the Force.com cloud platform," said George Hu, executive vice president, platform and marketing, salesforce.com. "Force.com is a proven enterprise platform that powers the most sophisticated apps in highly specialized industries, such as pharma. The expansion of our work with Veeva will accelerate pharma customer success with cloud computing."

Indian scientists show insoluble drugs can be taken orally in nano crystal form

Taking a big leap in how oral medicines are administered, Indian scientists have shown that producing nanoscopic crystals of a pharmaceutical product can allow the medication to be absorbed by the gut even if the drug is not soluble in water.

The study suggests that more than half of the medicinal drugs being developed by the pharmaceutical industry dissolve only very weakly in water, if at all.

This is a major problem for administering such drugs as it means they are not effective if taken by mouth.

The industry has developed many approaches to addressing this problem, such as adding a small quantity of an organic solvent, such as ethanol, to the mixture, coupling the drug with a charged ion to increase bioavailability and in more recent times using water-soluble "carriers", such as the ring-shaped cyclodextrin.

A much more effective approach would be to somehow make the drug soluble without resorting to such additives.

Scientists have, over the last decade or so, discovered that producing microscopic crystals of a pharmaceutical product can make it soluble in water even if the bulk compound is not.

The tiny particle size, means a much greater surface area to volume ratio giving access to more water molecules that can surround the particles, which is the essence of dissolving a compound.

This effect can then allow the particles to be carried across the lining of the gut wall where they would previously simply move past with no interaction.

The effect can be explained in terms of the physical chemistry and mathematics known to nineteenth century scientist Lord Kelvin, Herbert Freundlich, and Wilhelm Ostwald.

Now, R. Ravichandran of the Regional Institute of Education (NCERT), in Bhopal, India, has demonstrated that gymnemic acids derived from the herb Gymnema sylvestre , can be made more readily bioavailable by forming the active compounds as nanoscopic crystals, nanocrystals.

The compounds have medicinal activity in a range of diseases, in particular diabetes mellitus, with the native herb having been used in traditional medicine for several centuries.

Ravichandran's detailed examination of the physical and chemical properties of nanocrystals of gymnemic acids could provide important clues as to how to transfer the medical benefits of the herb to a regulated pharmaceutical product for further investigation and with a more strict profile in treating disease.

The study has been published in the International Journal of Nanoparticles.

Scientists Discover 16 Active Pharmaceutical Substances in Doñana National Park

The unfiltered pharmaceutical compounds present in Doñana National Park’s waterways pose eco-toxicological risks to aquatic organisms.

Wastewater treatment facilities were not designed with the pharmaceutical industry in mind, which may explain why they are increasingly incapable of filtering out the cacophony of drugs we now consume. After finding 16 different pharmaceutical substances in the waterways that flow through the Doñana National Park, scientists recommended that the surrounding wastewater facilities incorporate a tertiary treatment system in order to more effectively cleanse the water that is subsequently dumped into the Guadiamar River, Partido stream, and La Rocina stream.

According to Wildlife Extra, scientists from the University of Seville discovered the following pharmaceuticals in the Doñana National Park:

Five anti-inflammatory drugs (diclofenac, ibuprofen, ketoprofen, naproxen and salicylic acid)

A nervous system stimulant (caffeine)

Two antibiotics (sulfametoxazol and trimethoprim)

Two lipid regulators (clofibric acid and gemfibrozil)

An anti-epilepsy drug (carbamazepine)

A beta blocker (propranolol), and

Four hormones (three natural: oestrone, 17β-oestradiol and oestriol; and one artificial: 17α-ethynyloestradiol)

Ibuprofen is the most prevalent of all pharmaceutical compounds found in Doñana: 140kg of it is consumed and metabolized by human beings, and then discharged through their urine and faeces.

This discharge is then piped to the wastewater treatment plant, where only 60% of the substances are effectively removed before that water then travels to the river and streams.

Scientists warn that this contaminated water poses eco-toxicological risks to aquatic organisms, including Hydra attenueta. In a separate experiment, they discovered that exposure to such chemicals altered the genes in the liver and brain of Atlantic Salmon.

While not mentioned in this particular report, constructed wetlands – comprised of bulrushes and papyrus and other wetland organisms – have proven to be significantly more effective at filtering out substances that conventional wastewater treatment centers are unable to process. In the meantime, scientists have recommended the addition of a third treatment step that incorporates either oxidation or membrane systems to improve the quality of water discharged “24 hours a day, 365 days a year.”

“Now, the scientists will transfer these results to native species living in the water systems of Doñana in order to “better understand the way these compounds influence genetic expression,” Esteban Alonso, lead author of the study and a researcher at the Department of Analytical Chemistry at the US, tells SINC.

Sale of unexpired medicines permitted

he Madras High Court on Wednesday ordered the removal of seals placed on three pharmaceutical godowns, linked to the fake drugs scam, by the Inspector of Drugs and Inspector of Police from Kodungaiyur in March this year.

In an order, Justice N Paul Vasanthakumar directed the Inspector of Police, Kodungaiyur station and the Drug Inspector, Perambur Range, to remove the seals put up by them in the said three business premises in the presence of the representatives of the petitioner and permit the petitioners to sell drugs/medicines, for which the expiry period was not over and which were not identified as spurious medicines.

The court also permitted the petitioners to sell the unobjectionable drugs after getting clearance from the Drugs Inspector concerned.

However, the court observed that the objectionable drugs could be kept separately, either on the premises of the petitioners or at a separate place or the same could be taken away by Drug Inspectors for its custody with them.

Besides, the court also ordered de-freezing of petitioners bank accounts.