Animal testing

This implantable micro-machine can deliver medications from inside the body

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Scientists have developed a bio-compatible micro-machine capable of being implanted inside the body, where it could act as a wireless medical device to deliver drugs directly under the skin.

The device, which measures only 15 millimetres long, is actually a squishy version of a mechanism called a Geneva drive, which has been used in wristwatches going as far back as the 17th century. Only this time, it would be worn inside and not outside the body.

Most of today’s implanted medical aids are made from static components that don’t allow freely moving parts. And because they often include batteries or other kinds of electronics that are toxic to the body, they can create complications with the human tissue that surrounds them.

Of course, devices such as pacemakers have been successfully implanted in patients for decades, but compared to inflexible, metallic devices, researchers think soft, supple implants could make a range of new medical treatments possible in the future.

“Traditional implantable devices are made of silicon or metal, and there are certain manufacturing processes that you would use to make devices out of those materials,” researcher Samuel Sia from Columbia University told Abby Olena at The Scientist.

“But they don’t work on biological materials, which are much softer, and so we had to develop our own methods.”

To develop an implant with moving parts that could be safely implanted inside the body, the team turned to hydrogels – a material composed of polymer chains with high water content (over 90 percent), which makes it soft, flexible, and highly compatible with biological tissue.

Using a method to stack layered sheets of this hydrogel, the researchers can fabricate their squishy Geneva drive in about 30 minutes – but developing the technique and discovering the right materials to use took some eight years of research.

The team ultimately decided on polyethylene glycol (PEG)–based hydrogels, which are biodegradable and approved by the FDA for use in medical devices.

“Of course, you have other devices that are also made out of bio-compatible materials, but those are mostly passive devices,” researcher Albert van den Berg from the University of Twente in the Netherlands, who was not involved in the study, told The Scientist.

“[T]hese are active, command-able devices. It’s really a breakthrough.”

Each full revolution of the small gear rotates a larger gear by 60 degrees, exposing one of six potential drug reservoirs to an aperture, through which medication can be released to the body.

While the device isn’t a fully independent micro-robot, capable of acting on its own, it is a machine that can perform its function inside the body without any direct physical contact with the outside world – save the nearby presence of a single magnet.

In testing with mice bred to develop bone cancer (osteosarcoma), the researchers magnetically triggered the release of the chemotherapy medication doxorubicin over the course of 10 days.

The results showed that using the device with just 10 percent of a regular doxorubicin dosage was more effective in stopping tumour growth and killing cancer cells than conventional chemotherapy – with a 56 percent reduction in cancer cells for iMEMS, compared with 39 and 19 percent reductions for high- and low-dosage systemic treatments respectively.

The device was also less toxic to the subject overall than a conventional treatment, since such a reduced amount of chemotherapy medication was released.

While it’s early days for the technology as a whole, and these promising results have only been seen in mice so far, the researchers hope that one day their micro-machines could be used to deliver cancer-fighting medications in humans – or other kinds of drugs we need, like insulin.

“People are already making replacement tissues and now we can make small implantable devices, sensors, or robots that we can talk to wirelessly,” Sia said in a press release.

“Our iMEMS system could bring the field a step closer to developing soft miniaturised robots that can safely interact with humans and other living systems.”

The findings are reported in Science Robotics.

Source: 1

Health ministry bans “Draize” test in rabbits for eye irritation tests, dermal toxicity tests for skin irritation

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In line with the international trend towards replacing tests on animals with alternative methods, the Union health ministry has prohibited the use of “Draize” test in India which has been in vogue for the last more than 70 years for eye irritation tests and dermal toxicity tests for skin irritation/corrosion tests in rabbits. The ministry has now recommended the use of OECD (Organisation for Economic Cooperation and Development) validated non-animal alternatives.

According to the amended notification, GSR 897(E) dated 21.09.2016, in the Drugs and Cosmetics Rules, 1945, in Schedule Y, in Appendix III relating to Animal Toxicology (non-clinical toxicity studies), in paragraph 1, in sub- paragraph 1.4 relating to local toxicity, “the initial toxicity study shall be carried out by non-animal alternative tests as given in Organisation for Economic Cooperation and Development Guidelines”.

Likewise, in note (vi) relating to ocular toxicity studies (for products meant for ocular instillation), the notification states, “such initial toxicity studies shall be carried out by non-animal alternative tests as given in Organisation for Economic Cooperation and Development guidelines.”

India has been a full adherent to the Organization for Economic Cooperation and Development (OECD) decision regarding Mutual Acceptance of Data (MAD) since 2011. As a consequence, the data generated following OECD test guidelines and using Indian Good Laboratory Practice laboratories must be accepted in all the OECD member countries, and vice versa. The OECD estimates that adherence to MAD saves more than €150 million and scores of animals per year by avoiding needlessly duplicative testing.

The health ministry’s decision comes after a series of representations made by HSI/India, People for Animals and other stakeholders, informing the ministry regarding internationally recognized alternatives to “Draize” test.

The Draize test was developed more than 70 years ago to measure eye and skin irritation using rabbits, who are locked in restraints while a test chemical is applied to one eye or to the shaved skin on their backs. Animals are monitored for up to two weeks, without pain relief, for signs of chemical damage, which can include swelling, ulceration, bleeding and blindness. In addition to its obvious cruelty, the Draize test is not reliable or relevant to humans. A variety of validated and internationally recognized non-animal alternatives, including reconstructed human skin and corneal tissues, have been available for years — some since 2004. These 21st century technologies, deployed as part of a sequential testing strategy, allow for complete replacement of the Draize eye and skin tests with methods that are more reproducible and reflective of human responses.
Earlier this year, the Drugs Controller General India (DCGI) had constituted a committee to examine the feasibility of replacing the Draize test with alternative methods in Indian situation. The committee in its first meeting held on May 23, 2016 deliberated the issue and perused the related literature applicable globally vis-a-vis Schedule-Y requirement. It noted that several alternative tests are being evolved and validated to different stages. The OECD guidelines have also suggested use of alternative methods. The committee also noted that US FDA and European Union have also initiated the process of use of alternative methods.

Later in August this year, the Drug Technical Advisory Board (DTAB) had also recommended a two-year phase out period for the “Draize” irritation tests using rabbits. During this transition period, validated non-animal alternatives may be accepted in place of the previously mandatory animal tests, it recommended.

Source: 1

A new treatment stops OCD in mice in minutes

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Scientists have developed a new fast-acting treatment that can stop obsessive-compulsive disorder (OCD) behaviour in mice in a matter of minutes, which is a huge improvement on the weeks and months that these drugs normally take to have an effect.

The experiments so far have only been carried out on mice, but researchers think the same approach could work with people, meaning we could be closer to a treatment for OCD that’s effective and almost instantaneous.

Around 1 percent of the adult population in the US experiences some form of OCD, and half of those cases are classed as severe, so a fast and effective treatment would be incredibly welcome. The anxiety disorder shows up through intrusive, persistent thoughts and repeated, compulsive actions that interfere with a person’s normal day-to-day life.

To investigate what might be responsible for OCD-style behaviour in mice, researchers from Duke University in North Carolina zeroed in on a neuroreceptor called mGluR5, one of the proteins that helps control the brain’s response to outside stimuli. Once the activity of mGluR5 was blocked, the OCD-like behaviour in the test mice cleared up very quickly.

“The reversibility of the symptoms was immediate – on a minute time frame,” said senior investigator Nicole Calakos. Antidepressants used to tackle the same problems in mice were found to take weeks to have any effect, the same sort of timescale currently seen with human patients.

The discovery of the role of mGluR5 builds on prior work from 2007 also carried out at Duke. Researchers previously found that deleting a gene that codes for a protein called Sapap3 – which helps brain cells communicate – was enough to cause mice to show signs associated with OCD, including excessive grooming and displays of anxiety.

Now, nine years later, scientists have found a way to reverse that effect. “These new findings are enormously hopeful for considering how to approach neurodevelopmental diseases and behavioural and thought disorders,” said Calakos.

Sapap3 helps to organise connections between neurons, and without it mGluR5 isn’t properly controlled. The scientists also tried a separate test where mGluR5 production was boosted in ordinary lab mice, and sure enough the same anxious behaviour started.

With the mGluR5 receptor always on – due to the absence of a functioning Sapap3 protein – certain neurons in the brain work overtime to give the ‘green light’ to repeated actions like face washing.

The next step is to see if mGluR5-blocking medications can work in people, and the good news is that similar drugs have previously been part of clinical trials to treat Parkinson’s, which means the first steps have already been taken. Still, a lot more work needs to be done on identifying which compulsive disorders mGluR5 could be linked to in humans.

While a variety of psychotherapies and medications are available to try and keep OCD under control, there’s nothing anywhere near as quick and painless as this new treatment might prove to be, so we can’t wait to see where this research leads. 

The findings are published in Biological Psychiatry.

Source: 1, 2


CROs opt for computer model techniques to test cosmetics as ban on animal testing comes into effect

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India’s pre-clinical contract research organisations (CROs) like Bioneeds, Advinus Therapeutics, Syngene and Jai Research Foundation are now looking at non-animal tests like the in-vitro analysis and even considering the advanced computer modelling techniques which are far more reliable to deliver human-relevant results in a day, unlike some animal tests that require a few weeks.

With the prohibition of the animal testing by the Union government and the revision of the Drugs and Cosmetics Rules 1945 inserting a new rule after 148-B with 148-C to forbid animal testing for cosmetics, research institutes like the IISc, NCBS and JNCASR point out that globally sophisticated computer models which accurately predict drug reactions, techniques like the 3-dimensional human cell derived skin model, quantitative structure activity relationships (QSARs) help to replace the use of guinea pigs or mice generating accurate allergic response data.

The departments of pharmacology in international universities have preferred the computerised human-patient simulators to indicate the adverse drug reactions. India with its scientific prowess and research capability could easily adopt the same, stated IISc, NCBS and JNCASR.

Bengaluru-based Bioneeds India, an OECD GLP Certified Pre-Clinical CRO, has already adhered to the European Commission’s Scientific Committee on Consumer Safety (SCCS) SCCS/1297/10 issued on 8 December, 2009 which mandates use of validated alternative methods in toxicological testing. These are Local Lymph node assay, NRU Photo toxicity, Bovine Corneal Opacity Study (BCOP), Dermal percutaneous absorption study (rHES), Direct Peptide Reactivity Assay (DPRA) and In vitro dermal irritation study (Epiderm).

“We anticipated this some time back following the EU directives and finally the Indian government has also taken a stand to implement and passing the message to the global regulators that; India is on par with the ‘Be Cruelty-Free Campaign’. Our scientific personnel are armed with the know-how for in-vitro tests and have pioneered in standardizing and implementing the same. In fact, we are one among the premier CROs in the country to comply with global regulatory guidelines of the European Commission’s SCCS which is still in the preliminary stage of implementation in India,” Dr. SN Vinaya Babu, managing director & chief executive officer, Bioneeds India Private Limited, told Pharmabiz.

However, it would have been better if this decision to ban animal studies for cosmetics becomes a global mandate. India, China and South East Asia are seen as hubs by the US and European Union for pre-clinical research. With the revival of the global economy, there would be a number of opportunities for companies in the region. Therefore adherence to SCCS norms are the need of the hour to grab some of the potential business opportunities, said Dr Babu.

Source: PharmaBiz

Health ministry prohibits testing of cosmetic products on animals

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After releasing the draft amendment to ban the import of cosmetics tested on the animals recently, the union health ministry has now prohibited the testing of cosmetic products and ingredients on animals within the country.

Through a notification, the ministry has amended the Drugs and Cosmetics Rules 1945 to insert a new rule after 148-B and effected the ban on animal testing for cosmetics. “148-C prohibition of testing of cosmetics on animals- No person shall use any animal for testing of cosmetics,” said the gazette notification.

After approval from the Drugs Technical Advisory Board (DTAB), the ministry had issued the draft notification on January 14, amending the D&C Rules and invited the suggestions from the stakeholders within the mandatory period of 45 days.

“Objections and suggestions received from the public on the said rule have been considered by the central government. Now, therefore, in exercise of the powers conferred under section 12 read with section 33 of the Drugs and Cosmetics Act, 1940 (23 of 1940), the Central Government after consultation with the DTAB makes the rules further to amend the D&C Rules,” said the final notification.

Welcoming the notification, Humane Society International/India, said its high-profile Be Cruelty-Free campaign had been instrumental in convincing the Drug Controller General and the ministry of health and family welfare to end animal testing for cosmetics.

“We think this is a huge victory for animals in laboratories, the Be Cruelty-Free campaign and the dozens of legislators who wrote to the health ministry regarding this. India has taken a step forward in ethical consumerism and with the notification, will lead the world towards it too,” HSI said in a statement.

Recently the ministry has released the draft rule to ban the import of cosmetics tested on animals abroad. As per the notification, a new rule (135-B) will be inserted under the Drugs and Cosmetic Rules, 1945 to ban the imports.

  Source: PharmaBiz