Stephanie Sutton was an assistant editor at Pharmaceutical Technology Europe.

Stephanie Sutton

	This week an interesting report was released about the use of gelatine in medicines. Most of us are comfortable with the use of animal products as ingredients, but for vegetarians or other people that follow restrictive diets it can be an issue.  Anybody who falls into this situation should be able to choose whether they will or won’t take a particular product, but the report highlights the fact that many people do not realise that their medicines contain gelatine. In particularly, many vegetarians may unknowingly be prescribed medicines that contain animal derivatives.

	As such, the authors of the report, published in the 

are calling for clearer drug labelling for such medicines.

	It’s not just vegetarians either who may want to know more about the medicines. Most people are taking greater interest in the ingredients in all the products they consume, whether it is a food or a medicine.

	According to the study, doctors only usually consider the API when prescribing a medicine, ignoring the excipients that make up the bulk of a tablet or capsule. However, many drug excipients contain gelatine, particularly urological drugs and generic drugs. The study authors conducted a survey with the aim of finding out how many patients had been inadvertently prescribed medicines containing gelatine.

	Five hundred patients were surveyed, of which around 200 were found to be following a restricted diet whether for cultural, religious or personal preferences. Forty nine of these were found to be already taking medicines that contained gelatine.

	Many vegetarians will still take medicines that contain animal products if there is no alternative, but the reports says that more should be done to help these people. At the very least, I think that people should be aware of what is in their medicine so that they can make their own decisions.

quotes the study authors as saying that, “every doctor needs to be aware that it is not just the active drug being dispensed but a whole group of other agents which may have relevance to an individual patient’s compliance with treatment when oral treatments are prescribed”.

	Vegetarians now have many more food choices than they did ten years ago. For instance, almost every restaurant has one or more vegetarian options on the menu and even traditionally non-vegetarian friendly products, such as gummy sweets, are available in animal derivative-free form. Most vegetarians probably take it for granted that their medicines are also free of animal products. Making vegetarian-friendly products is also not typically a top concern of manufacturers, who must, of course, focus on efficacy and safety.

	However, many medicines are vegetarian friendly as there is a growing trend for manufacturers to move away from the use of animal products, but this isn’t possible for all medicines. For those that are free of gelatine and other related ingredients, however, it could represent an important marketing point, particularly for over-the-counter medicines.

	According to the BBC News piece, a spokesperson for the Association of the British Pharmaceutical Industry explained that all medicines in the EU are accompanied by a leaflet listing all the ingredients. Unfortunately, many patients do not always bother to read this list. Clear labelling would certainly be a way to enable patients to know more about what they are taking.

	Nowadays, many medicines are vegetarian friendly as there is a growing trend for manufacturers to move away from the use of animal products, but this isn’t possible for all medicines. For those that are free of gelatine and other related ingredients, however, it could represent an important marketing point to reach certain patient groups, particularly for over-the-counter medicines.

Articles

This week an interesting report was released about the use of gelatine in medicines. Most of us are comfortable with the use of animal products as ingredients.

Clearer Labelling for Vegetarian Medicines

Last week, counterfeits of the anti-cancer drug Avastin were discovered in the US and this week fake pharmaceuticals continue to occupy headlines.

		Investigations are continuing in the Avastin case. Although neither Roche nor the FDA have released new statements since last week, several third-party media reports say that investigators have traced the source of the counterfeits back through a path from the US, to the UK, to Denmark, Switzerland and finally to a company called SAWA in Cairo (Egypt). However, it seems as if SAWA may not actually exist. Or if it does, it’s certainly not a legal company.

, a spokesman for the Egyptian health ministry said that official checks had found that SAWA was not registered with the ministry in any capacity, which makes it illegal for the company to deal in pharmaceuticals.

		And it’s not just the US that is dealing with counterfeits this week; in the UK, authorities on 

 seized a large quantity of fake sex drugs worth an estimated £140000. Two men have been arrested and the UK’s Medicines and Healthcare products Regulatory Agency added that the haul may have included around 6000 counterfeit copies of Eli Lilly’s Cialis drug, although this needs to be confirmed by testing.

International Journal of Clinical Practice

 that warned of the increasing numbers of fake drugs entering legitimate supply chains. According to the article, global sales of counterfeit medicines are worth more than $75 billion, and have doubled in just five years between 2005 and 2010.

		Counterfeit drugs are traditionally more prevalent in developing countries where supply chain security and enforcement systems are weaker. However, the fact that counterfeits are increasingly entering the more heavily regulated supply chains of the west goes a long way to saying that counterfeiters are getting smarter – and more determined to break into high-value markets, such as anticancer drugs.

		In the UK, for instance, there have been nine recalls of counterfeit medicines in the past three years. In 2011, an enormous £4.7-million counterfeit pharmaceutical scam was also uncovered in the UK. Peter Gillespie was 

 in April 2011 for plotting to bring two million counterfeit drugs worth £4.7 million from China to the UK.

		Although counterfeiters are becoming more aggressive, regulators are also stepping up the fight. In Europe, the Falsified Medicines Directive (due to come into force in 2013) will increase controls across the EU. Companies will be required to add safety features to packaging and online pharmacies will also be targeted. Other initiatives are also taking place. For instance, the European Federation of Pharmaceutical Industries and Associations (EFPIA) has been working with other groups and organisations to identify options for establishing effective solutions to verify medicines in Europe.

		The US is also making efforts to fight counterfeits. Last year, the FDA in a joint effort with several other government agencies and departments issued a report recommending a number of items to prevent counterfeits from entering the US. In January this year, the US Pharmacopeial Convention also proposed a set of best practices to ensure that medicines could be traced back to their original manufacturer.

, you’ll be able to read more about counterfeits. We’ll be publishing two articles examining the growing incident of counterfeits in Europe and the US, respectively.

Counterfeit Woes in the West

Pfizer has signed an agreement with the Chinese biopharmaceutical company Zhejiang Hisun Pharmaceuticals with the objective of establishing a $545-million 

 to develop and commercialize branded generic medicines in both China and the global market. The agreement that was signed is a framework agreement that Pfizer described as an “important milestone” in the formation of a joint venture between the companies.

The agreement builds on a memorandum of understanding that the companies signed in 

 on their intention to establish a joint venture.

According to the framework agreement, the potential joint venture will be called Hisun Pharmaceuticals Co. Hisun will own 51% and Pfizer will own 49%, and the aggregate and registered capital will be $295 million and $250 million respectively. The companies will be focusing on the potential for manufacturing cooperation, broader commercialization of medicines through local and global sales and marketing infrastructures, and the R&D of off-patent medicines. After the joint venture has been formed, both companies will be able to contribute selected existing products, manufacturing sites, cash, and other relevant assets. 

Pfizer believes that generic medicines represent one of the fastest growth segments in the global pharmaceutical market. In China, branded generics account for 60% of the domestic market and the country is expected to become the world’s second largest pharmaceutical market by 2015.

The framework agreement was signed at the Sino–US Economy & Trade Forum held in Los Angeles late last week during the US visit of China’s vice-president Xi Jinping. The US Secretary of Commerce, John Bryson, as well as other senior officials from the Chinese and US governments attended the event.

Pfizer has signed an agreement with the Chinese biopharmaceutical company Zhejiang Hisun Pharmaceuticals with the objective of establishing a $545-million joint venture to develop and commercialize branded generic medicines in both China and the global market.

Pfizer, Zhejiang Hisun Pharmaceuticals Sign Generic-Drug Deal

Much negative criticism has been directed at the pharmaceutical industry’s perceived lack of innovation in recent years, but one area that has received a lot of attention is neglected diseases. One of the latest developments that I’ve read about is an EU-funded project led by GlaxoSmithKline to develop new treatments for multiple drug resistant tuberculosis (TB).

Open Collaborative Model for Tuberculosis Lead Optimisation

 (ORCHID) project is focused on lead optimisation and the preclinical development of potential TB treatments. In particular, the researchers will be looking at three main areas:

			New InhA inhibitors - the project has identified a chemical series that can inhibit a recognised TB target. Tool compounds in the same series may also have potential against multidrug resistant strains of the disease.

			B-lactams - research has suggested that a novel approach could make the broad-spectrum antibiotics effective against TB.

			Whole-cell hits - compounds that were active against TB in high-throughput screening, but whose mode of action is unknown.

		A preclinical package is said to be already in place for some of the above, but further work is necessary for others to justify progression to preclinical and clinical development.

		ORCHID began in 2011, but earlier this week a 

 was released to say that Nanologica, a Swedish company with expertise in nanomaterials, had joined the project. Nanologica’s first goal will be to examine formulation problems associated with the poor water solubility of certain compounds.

		“Our role is to provide formulation and drug delivery solutions to the poor solubility typical of potent anti-tubercular drug compounds, using our porous silica particles, which have been proven to enhance the pharmacokinetic properties of APIs, in particular the bioavailability of poorly soluble compounds,” Dr. Alfonso Garcia-Bennett, Head of R&D at Nanologica, told me in an email.

		ORCHID has received funding of more than 5 million Euros from the European Commission’s Seventh Framework Programme for Research and Technological Development. Further funds will be provided by project partners, bringing the project up to 10 million Euros.

		Big Pharma names are often the first to come to mind when people think of new treatments, but it’s important not to underestimate the benefits that more niche players can bring to R&D. Garcia-Bennett was very excited when speaking about the project because of the benefits it could have for Nanologica. “The project marks a milestone in the development of our functional excipient line of porous materials. It enables us to validate our particles in a commercial context; from both regulatory and clinical perspectives, together with the best from the pharmaceutical industry and with partners committed to the goals of the project,” he said.

		The ORCHID project will also be calling on the expertise of several academic institutions, including universities in the UK, Slovenia and France.

Alliance between pharma and nonprofits to speed development of tuberculosis therapies

Coordinated global health efforts pay off for malaria 

Much negative criticism has been directed at the pharmaceutical industry’s perceived lack of innovation in recent years, but one area that has received a lot of attention is neglected diseases.

Nanomaterials and TB treatments

The South African government is involved in talks with the Swiss biopharmaceutical company Lonza regarding a joint venture to construct the country’s first plant to manufacture APIs for antiretroviral (ARV) medicines. The government is investing approximately 1.6 billion Rand ($206.6 million) in the joint venture, which will be called Ketlaphela, a Sesotho word that means “I will live or survive.”

, South Africa’s Minister of Science and Technology, Naledi Pandor, said that Lonza and Pelchem, a speciality chemical manufacturer and the sole producer of flourochemicals on the African continent, were involved in the joint venture. In a 

, Lonza confirmed that it was involved in negotiations, but emphasised that discussions were still at an early stage and that nothing had been signed.

More than 5.5 million people in South Africa live with HIV/AIDs and the country has the world’s largest ARV program, accounting for 20% of the global demand for ARVs by volume. A new government policy is expected to increase the number of patients taking ARVs from 1.9 million at the end of 2011 to approximately 3.5 million in 2016.

Most of the country’s medicines currently in use are manufactured by local pharmaceutical companies, but all of the APIs for ARV medicines are imported. The South African government hopes that the venture will reduce the country’s dependence on imports and mitigate its deficit, to which pharmaceuticals are the sixth largest contributor. The venture would also offer security of supply for priority drugs.

At the moment, the manufacturing plant is planned to be operational in 2016. It will be small scale and will be located in Pelindaba. In addition, the plant is expected to provide key support to small research companies and institutions in the country. 

The government expects the plant to create 350 jobs in primary and secondary manufacturing, as well as an additional 1800 to 2250 sustainable indirect jobs. As much as 60% of the government’s 1.6-billion Rand ($206.6 million) investment will be spent on local procurement.

The South African government is involved in talks with the Swiss biopharmaceutical company Lonza regarding a joint venture to construct the country's first plant to manufacture APIs for antiretroviral medicines.

South Africa Plans Joint Venture for New API Plant

The EMA has published a guideline that addresses the influence of patients’ genetic variability on drug pharmacokinetics. The guideline on the use of pharmacogenetic methodologies in the pharmacokinetic evaluation of medicinal products clarifies the requirements for drug developers to analyse the effect of genetic variability on their medicines. Adopted by the EMA’s Committee for Medicinal Products for Human Use in January following a public consultation, the guideline is expected to come into effect on 1 August 2012. 

Genetic variation can affect the body’s absorption, distribution, metabolism and excretion of medicines, which can subsequently impact a medicine’s benefits and risks. Although pharmacogenetics are not equally important for every drug, the guideline recommends that prospective banking of DNA for genotype analyses be conducted in all clinical phases of development. Even if there is no obvious indication of a genetic influence on pharmacokinetics, effects may be identified at later stages of development or in postmarketing, which was the case for tamoxifen and clopidogrel where activation by polymorphic enzymes was identified during pharmacovigilance monitoring. 

According to the guidance, studies of the effect of pharmacogeneitcs will usually be required when the magnitude of interindividual variation in drug exposure is high enough to potentially affect a medicine’s safety and/or efficacy. The guideline provides recommendations on where pharmacogenetics should be implemented into the drug development process and applies mainly to small-molecule drugs, as the genetic effects on the pharmacokinetics of biological drugs are not yet as well understood. 

recommendations and requirements for study designs, subject selection and sampling

how to evaluate the clinical impact of genetic differences between patients  and recommendations for further studies

possible consequences of differences and the impact on treatment recommendations and labelling

consideration of drug–drug interactions

effects of impaired or immature organ functions on pharmacogenetics related pharmacokinetic studies.

The EMA has published a guideline that addresses the influence of patients? genetic variability on drug pharmacokinetics.