Pharma Focus Asia - Issue 26

Issue 26 2017

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Patient Recruitment An industry challenge Plotting Efficient Paths for Clinical Development Trends in Pharma Export Industry in India

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Foreword

Patient Recruitment and Retention Creating Effective Strategies From initiation to marketing of the drug, compounds face numerous challenges to become an approved drug. Apart from preclinical, financial and approval stages, successful recruitment of patients for conducting clinical trials is one of the most challenging aspects. Factors like lack of patient education about clinical trials and complex study designs are considered the main reasons for delay in recruitment. Patient retention in the process of conducting trial affects conclusive results.

Trial participants may drop due to variety of reasons like lack of awareness, complexity of study protocol, or a fear of side effects. Retaining patients on protocols from start to finish can be just as challenging as recruiting enough people to start off.

According to a survey conducted as a pilot study on seventy-three investigators from four zones, frequently encountered challenges in subject recruitment were complexity of study protocol (38 per cent), lack of awareness about clinical trials in patients (37 per cent ), and socio-cultural issues related to trial participation (37 per cent). Almost 50.7 per cent of participants agreed that interacting with medical community in vicinity of the study site and educating patients about clinical trials during routine outpatient department visits (46.6 per cent) would enhance recruitment. Experiencing a serious adverse event, the subject's fear for study procedures (47 per cent) and side effects (44 per cent) were thought to have a moderate effect on subject retention.

Taking patients’ feedback on their experience in completing / discontinuing the trial may provide insight on how to improve the participants’ experience. Researchers at Nationwide Children's Hospital, US, noted that after the stakeholders' recommended changes were adopted into the study, the enrollment rate increased from 65 per cent to 95 per cent and the retention rate increased from 58 per cent to 85 per cent.

Relationship between site staff and the participants also enhances recruitment and retention.

Recruiter communication behaviour could improve the probability of encouraging ambivalent patients into studies and lead to benefits for patients.

Apart from significant investment in infrastructure and perfect site management, special focus is required in development, testing and implementing processes to encourage recruitment and retention and make the trial successful. Successful clinical trials help change the future of medicine and improve millions of lives.

In the cover story, Mary Pan, VP Asia Pacific, ICON plc., Japan, provides a perspective on how different regions are evolving to meet the challenges related to patient recruitment and retention in clinical trials and how technological advancements are affecting this scenario.

Prasanthi Sadhu Editor

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Contents COVER STORY

34 Patient Recruitment An industry challenge Mary Pan, VP, Asia Pacific, ICON plc., Japan

STRATEGY

MANUFACTURING

06 Indian Pharma Companies Need Supply Chain Transformation

Unlocking growth

40 Trends in Pharmaceutical Packaging and Delivery

Abhishek Malhotra, Partner, AT Kearney, India

Kaushika Madhavan, Partner & Head, Strategic Operations Practice AT Kearney India

Amit Saharia, Principal, AT Kearney, India

11 Generics in Switzerland

The portraito

Troy Player, Vice President and Managing Director, Asia Pacific, West Pharmaceutical Services, Inc., Singapore

48 Our Esteemed Clients 54 Research Insights 58 Books

Axel MĂźller, Managing Director, Intergenerika, Switzerland

16 Plotting Efficient Paths for Clinical Development

George Yeh, President, TLC, Taiwan

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20 Trends in Pharma Export Industry in India

Piyush Gupta, Associate Director, GNH India

RESEARCH & DEVELOPMENT 25 Biologics and Biosimilars

Promising field for medicines for the future

Dhananjay Patankar, Head, Pharmaceutical and Biopharmaceutical Development, Syngene International Ltd, India

28 Wearable Large Volume Drug Delivery Devices

Hold key to pharmaceutical lifecycle management, patient preference Michael D Hooven, President and CEO, Enable Injections Inc., USA

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Advisory Board

Editor Prasanthi Sadhu Alan S Louie Research Director, Health Industry Insights an IDC Company, USA

Christopher-Paul Milne Director of Research, Tufts Center for the Study of Drug Development, Tufts University, USA

Douglas Meyer Senior Director, Aptuit Informatics Inc., USA

Frank Jaeger Regional Sales Manager, Metabolics, AbbVie, USA

Georg C Terstappen Director and Head of Biology, Neuroscience Discovery AbbVie Deutschland GmbH und Co. KG, Germany

Kenneth I Kaitin Director and Professor of Medicine, Tufts Center for the Study of Drug Development, Tufts University, USA

Laurence Flint Head Clinical Research Cough, Cold & Respiratory Disease Novartis Consumer Health, Inc., USA

Neil J Campbell President & CEO, Helomics Corporation HealthCare Royalty Partners University of Liverpool, UK

Editorial Team Grace Jones Vijaya Lakshmi Art Director M Abdul Hannan Product Managers Jeff Kenney Senior Product Associate David Nelson Product Associate Tina Williams Peter Thomas Circulation Team Naveen M Nash Jones Sam Smith Subscriptions In-charge Vijay Kumar Gaddam IT Team Jareena K Ranganayakulu V Sankar K Uday V Head-Operations S V Nageswara Rao

Pharma Focus Asia is published by

In Association with

A member of

Phil Kaminsky Chair, Department of Industrial Engineering and Operations Research University of California, Berkeley, USA

Rustom Mody Senior Vice President and R&D Head Lupin Ltd., (Biotech Division), India

Sanjoy Ray Director, Strategic Alliances & Health Innovation Merck, US

Confederation of Indian Industry

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The products and services advertised are not endorsed by or connected with the publisher or its associates. The editorial opinions expressed in this publication are those of individual authors and not necessarily those of the publisher or of its associates.

Copies of Pharma Focus Asia can be purchased at the indicated cover prices. For bulk order reprints minimum order required is 500 copies, POA.

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Strategy

Indian Pharma Companies Need Supply Chain Transformation Unlocking growth

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ndia has emerged as one of the world’s fastest growing pharmaceutical markets over the past decade.

The industry saw a growth of around 18 per cent per annum between 2005 and 2015, and now stands at US$30 billion.

The generic drug sector expanded at an

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even faster pace of 22 per cent per annum during the same period and now accounts for 20 per cent share of global exports by volume.

The phenomenal growth is expected to continue in the coming years, with India’s pharmaceutical sector forecast to nearly double to US$55 billion by 2020.

The generic drug sector is expected to capture 6 to 7 per cent of the US$760 billion generic drugs market by 2020.

With India having the highest number of

Strategy

India’s pharmaceutical companies have a unique opportunity to lead global growth for years to come.

However, there is a significant gap between the strategic vision and operational realities of the sector. Firms are facing challenges on multiple fronts in their supply chains. They need to overcome these hurdles to unlock their full potential.

Abhishek Malhotra, Partner, AT Kearney, India Kaushika Madhavan, Partner & Head, Strategic Operations Practice, AT Kearney India Amit Saharia, Principal, AT Kearney, India

FDA approved drug manufacturing sites - second only to the US, these numbers seem achievable.

However, while India’s growth trajectory looks promising on the surface, it is evident that there is a significant gap between the strategic vision and operational realities of the sector. Indian pharmaceutical companies are facing a unique set of challenges that are creating significant pressure on them to transform their supply chains.

Simply put, a supply chain refers to the combination of organisations, people, activities, and resources that are involved in moving a product or service from a manufacturer to the customer.

Indian pharmaceutical companies are facing hurdles on multiple fronts in their supply chains.

Key hurdles

As part of our efforts to assess the state of the pharma supply chain in India, which serves local and global markets, we conducted a study in collaboration with the Organisation of Pharmaceutical Producers of India (OPPI) and the Indian Pharmaceutical Association (IPA).

As part of this study, we interviewed CEOs and supply chain executives in medium and large Indian pharma companies. The executives highlighted four key challenges they are facing.

Quality and regulatory issues: Quality continues to be a hot topic in the industry. With 600-700 FDA approved sites in India, global regulatory agencies have been inspecting sites with increased regularity, with more than 800 issues identified by the US FDA

over the past eight years. In 2015, ten companies were issued warning letters, a 25 per cent increase from 2014.

Quality issues have deepened and widened over time and an increasing number of these are occurring across the value chain. These range from issues at the procurement level over quality of raw materials, as well as at the manufacturing stage where plant shutdowns and inability to get necessary certifications have created unused capacity. Lack of quality control at the R&D stage has also led to more failures of trial batches, causing delays in product launches.

Product proliferation: Indian pharmaceutical companies are expanding their portfolio at a fast pace. This has been driven in part by new product www.pharmafocusasia.com

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development, new dosage forms, enhanced formulations, and changes in packaging and labelling to cater to new markets. Indian players launch anywhere from 15 to 30 products / SKUs a year.

Several underlying factors have contributed to this including changing demographics which has seen the rise of non-communicable diseases such as diabetes, chronic pain and cardio vascular problems in India. Increased competition, which fuels the need to constantly innovate and varying regulatory requirements across multiple markets are the other key driving factors.

This fast-paced product proliferation has several implications for the supply chain, including higher manufacturing and distribution costs, more inventory, and a larger supplier base.

Supply chain fragmentation: India’s supply chain network is very complex making it even tougher to manage properly. Companies manage over 15,000 raw materials across over 10,000 facilities clustered around zones spread over five to six states and that’s before we move down the chain to distribution. The sheer number of players at each stage with varying requirements, lack of clear categorisation, lack of proximity to the manufacturer, and differing degrees of quality standards are clear challenges.

As a result, production schedule changes are becoming more common because of poor supplier service levels, further affecting the ability of the supply chain to make and deliver on time.

With two thirds of the global pharma industry being outsourced, decentralised R&D-where companies use multiple third party centres at different stages of development-creates a convolution of technology and data transfer, lengthening timelines for regulatory approval, increasing costs to deal with discrepancies, and reducing plant utilisation.

Infrastructure gaps: India has had a long-term struggle with improving its

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A few leading companies have paved the way in taking structured initiatives to boost their quality standards, receiving positive affirmation from global regulatory bodies such as the FDA.

the value chain. However, companies are still unable to ensure a product is stored at the required conditions throughout its transition.

India’s cold chain market is fragmented itself with more than 3,500 companies. Most are in dire need of both connectivity and technology. These gaps are not only a hurdle to the sector’s growth, but also pose a threat to patients who receive poorly handled drugs.

Unlocking growth

Given these challenges, Indian companies need to design a supply chain that is more adaptive, flexible and responsive to the changes. This can be done by focusing their efforts on four dimensions: Reducing complexity:

infrastructure. Less than five per cent of roads are highways, the railway system is simply inadequate, and the airways are underutilised. There are also gaps in storage and power supply.

In terms of storage, the lack of a robust cold chain network to support the supply chain represents a significant gap in today’s pharma infrastructure.

Drugs have varying storage requirements to ensure that potency is maintained throughout their shelf life. Moving specialty products and vaccines requires continuous monitoring at all stages of

India’s pharma supply chain is crippled with end-to-end complexity. Reducing this complexity can unleash an array of benefits. Efforts should be focused on these top three priorities for immediate, actionable results: • Consolidating and optimising the network as a whole, supporting seamless communications across suppliers, manufacturers, distributors, and customers • Tailoring visibility of supply chains, segmenting consumer needs, product types, product attributes,

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and markets. This will be crucial to improve efficiency • Handling the portfolio’s complexity both upstream (R&D portfolio proliferation) and downstream (product SKU proliferation), which will optimise capacity and resources upstream and kill underperforming SKUs, resulting in immediate cost cutting.

Creating agility and visibility :

In addition to changing patient needs and shifting disease patterns, the global market is experiencing more frequent drug shortages and communicable disease outbreaks. It is vital that pharma companies are ready to react to such market changes if they want to be best in class performers.

Ensuring that the supply chain is integrated with Sales and Operations Planning (S&OP) processes and commercial strategies will enable pharmaceutical companies to move from a ‘planning for convenience’ model to a ‘planning for market’ model.

Based on our experience, companies see a 10 to 20 per cent increase in service levels (from the current average of about 60 per cent) simply by streamlining their S&OP processes, which typically leads to a 1 to 2 per cent increase in the top-line.

•

• • •

operating procedures, supported with regular compliance training Enforcing a ‘quality culture’ from senior leadership, targeting the message across the organisation with supporting documentation of practices that can be followed by all Establishing data integrity organisation with data integrity officer lead Conducting routine internal audits by both global and local audit and compliance committees.

Implementing technologically advanced systems across network to reduce manual error: lab information management systems and document management systems.

Using tech across supply chain:

Technology remains one of the most important areas for pharmaceutical companies to focus on. One immediate result of using technology is greater transparency, which leads to better decision making. Technology can be used to integrate all functions across the network, increase visibility of products across the value chain, and automate processes to improve the supply chain’s responsiveness and reliability.

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A transformation of the supply chain in India’s pharma industry is in immediate need. However, a total revamp cannot be done in isolation. There are some things beyond the control of the industry that can only be overcome by strong collaboration with government and industry bodies.

The recent conversations between government and industry to combat India’s dependence on China for Active Pharmaceutical Ingredients (API) are a great example of such collaboration.

For the India pharma industry to realise its full potential the government and industry need to work together to eliminate external factors by enforcing regulatory standards and ensuring overall improvements to the pharma ecosystem and the country’s infrastructure.

This will create the right conditions for India’s pharma sector to transform its supply chain and support the industry as it grows.

Whether the prescription is heeded is another question.

Abhishek Malhotra is a Partner with AT Kearney and a member of the Consumer Industries & Retail Products Practice. Abhishek is an experienced management consultant and has worked with many leading companies and organizations to help them address their toughest business challenges. Abhishek has an MBA from Indian Institute of Management (IIM) Ahmedabad and Bachelors in Electronics Engineering from Punjab Engineering College (PEC) Chandigarh.

A u t h o r BIO

Building robust quality and compliance system :

There is an immediate need for quality processes to be tightened.

It is imperative to have a strong quality organisation with visibility and oversight across all practices in the supply chain, both internal and external. A few leading companies have paved the way in taking structured initiatives to boost their quality standards, receiving positive affirmation from global regulatory bodies such as the FDA. The following five internal initiatives can have a sizeable impact on quality systems: • De ve l o p i n g u n d e r s t a n d a b l e , executable, and compliant standard

External factors

Amit Saharia has 13 years of global management consulting experience with top tier strategy firms spanning private as well as public sector clients. He has advised leading global companies across multiple sectors including Pharmaceutical and Healthcare.

He has deep business understanding and strategic operations experience in end-to-end value chain functions.

Kaushika Madhavan has over 19 years of experience in consulting and across industry. He has assisted clients across multiple sectors including Pharmaceutical and Healthcare. His areas of expertise include Strategy Formulation & Articulation, Business Planning as well as Supply Chain Design & Management, among others.

Strategy

Generics in Switzerland The portrait

The article talks about the Swiss Generics market, the penetration rate of generics in Switzerland; why generics are a safe, and smarter choice, manufactured to modern standards with affordable prices; and the threat of government forcing generic companies to benchmark their prices to nine European countries by 2017.

Axel MĂźller, Managing Director, Intergenerika, Switzerland

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n 2015 the market reached 637 million Francs (US$648 million), seven per cent growth in value over 2014, but market penetration still lags considerably behind the OECD average. The reason the generics market is not yet fully developed in Switzerland is in large part due to a lack of incentives for doctors and pharmacists when it comes to prescription. The Swiss generics market is still not fully developed. When you look at the market share and penetration of generics in this country, it does not compare to markets such as Germany, the UK, France, or the Netherlands.

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within the Swiss pharmaceutical market was 19 per cent in 2015 in terms of value, and 32 per cent by volume. Also the penetration rate in this comparatively small country is still rather low, and must be expanded. The member companies of Intergenerika have been working hard on the educational front to ensure that pharmacists, doctors and patients have a more balanced view of generics. There has been a lot of work done to convey to highly brand-conscious Swiss people the point that generics are not of an inferior quality to the originator product. Generics are high-quality, off-patent products. I would even go so far as to say that they are sometimes of a superior quality with regard to the respective originator product.

Patented products have usually been on the market for 10 years or longer before a generic alternative is launched. Over this time, the product has been advanced in many ways, such as modern dosage forms or package varieties. The side-effect profile of generic products are well known, they are manufactured to a modern standard, and are on offer at more affordable prices.

In times of austerity they are the optimal choice and are increasingly seen as the indispensable alternative.

Lack of incentives, no obligation

The reason the generics market is not yet fully developed in Switzerland is in large part due to a lack of incentives for doctors and pharmacists when it comes to prescription. There is even a disadvantage for a self-dispensing doctor or pharmacist, since they receive a lower profit margin.

In Switzerland doctors are free to prescribe what they consider to be the best available product; they are under no obligation to prescribe a generic, and the same is true for the pharmacist. It is true that when purchasing a generic the patient has to cover 10 per cent of the costs out of their own pocket, whereas that per centage can rise to 20 in the case of an originator product. Yet this incentive to buy a generic is reduced by the patient’s sickness-fund, which frequently covers all the costs. Intergenerika is asking the government to create further incentives 12

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In terms of value, the total share of generics within the Swiss pharmaceutical market was 19 per cent in 2015 in terms of value, and 32 per cent by volume.

advantageous when it comes to reducing costs, it is problematic for the patient.

Germany has a so-called rebate-system, where sickness funds negotiate a contract with the pharmaceutical company, and the patient is then obliged to switch to a lower priced product the next time they go to the pharmacist. Different brands, namely drugs with the same ingredients but with different presentations, frequently lead to overdosing by confusing the patient.

In Switzerland we do not use such a system; the patient and the doctor can decide what is best for them. This is an important principle that must be respected.

Generics are not too expensive

for doctors and pharmacists to prescribe generics. Not with standing a lack of incentives, today more and more sickness funds and patients understand the value of generics when it comes to reduce overall healthcare costs. We are convinced that the growing penetration of generics will continue in the years ahead.

Advocating freedom of choice

Contrary to other countries and generic associations which advocate mandatory substitution in Switzerland we support more individual responsibilities for doctors and pharmacists. Imprinted within the Swiss DNA is the right to make a choice, notably when it comes to their medicines. At Intergenerika, we are not asking for a disadvantage when it comes to buying the originator product, or any particular advantage for generics: we simply say, let the doctor and the patient decide what is best for them.

We encourage the use of generics, as the more modern and affordable option.

Nevertheless, the barriers to generic penetration mentioned earlier must be removed. While in Switzerland, doctors and pharmacists have remained in control of the process in Germany the decisionmaking power has moved from the doctors and pharmacists, to the sickness funds, which reimburse only the most cost efficient product. While the approach employed in a country such as Germany is

Generics in Switzerland are not too expensive particularly with respect to their high quality and the unique service package that are offered. One also has to take into account the costly approval procedures by Swissmedic, the Swiss Health Authorities. The problem of the comparison with foreign prices is the countries we are comparing prices to. One can not compare Swiss generic prices to those in Germany, where there is a rebate system that penalises the patient. If you compare our prices to those in France, Finland, Austria or Belgium, markets with systems comparable to the Swiss healthcare system, there is only a 30 to 40 per cent price difference. If you compare the Swiss generics market to those in the UK, Denmark or the Netherlands, where you have extremely high generic penetration, clearly we cannot compete.

The number one issue is the selection of the reference countries.

Reasons for higher costs

Costs are, in general, higher in Switzerland than in many other European countries.

As mentioned earlier, before a product can be launched on the market, it must receive approval from Swissmedic, which asks for additional trials, rather than merely accepting results from the EU. Such additional trials have a cost. One example for the bewildering approval requirements of swissmedic are oral inhalational

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supply shortages. Another issue is that if generic prices continue to be forced down, smaller companies could be forced off the market, leading to a monopoly, with all the known disadvantages. The government must realise that if they go ahead with their proposed price cuts, it may lead to short-term savings over the next few years, but will result in a longterm damage of our industry.

Wrong scapegoats

An article published in November 2016 makes it clear that it is wrong to blame generics for the increase in healthcare costs. It calculates that only 0.63 billion Swiss francs of a total of 75 billion of healthcare costs are caused by generics.

If prices for generics would drop to the level requested by the price supervisor reduction of healthcare costs would not exceed 0.42 per cent.

Intergenerika’s key messages at a glance

1. Our vision: Generics are the preferred choice for medicines 2. Our Mission: Intergenerika adovocates a highly qualitative and secure supply of generics for Swiss people at affordable prices 3. Generics should be perceived as the better medicines. Compared with the originator they are more modern medicines partially offering improved galenics – and at a more favourable price 4. Generics are far more than only active substances-namely well conceived and proven high quality pharmaceuticals which have to go through additional national approval procedures 5. A switch to a "lowest price system" would only produce losers: Patients and

A u t h o r BIO

products with known sub-stances which are used for treatment of bronchial asthma and chronic lung diseases (COPD) also called "asthma generics".

There is no plausible explanation why those asthma generics are excluded from the Swiss market, although they have proved over years to be effective and well-tolerated in neighbouring countries.

Unfortunately the “asthma generics” are no isolated case. With its rigid and not very cooperative stance, the regulatory authority is preventing the realisation of potential large savings. Furthermore, all the key healthcare stakeholders – the wholesaler, the pharmacists, the doctor – enjoy higher salaries than in the majority of other European countries. A pharmacist in Switzerland earns double what a German pharmacist receives. In markets such as Germany and the Netherlands, companies can launch the pack size which is the most profitable for them, and avoid having to launch the ten-pill package. In Switzerland, we are asked to launch the full range of package sizes, which results in additional costs. The principle factor behind the differentiation in pricing, however, is that the market in Switzerland is rather small compared to a country such as Germany, and therefore you do not have economies of scale. If the Swiss government follows through with its intention to introduce a reference price system in 2019 where only the cheapest product would be reimbursed, the generics industry could be irreparably harmed.

Today the majority of Swiss generics companies are no longer family owned, but belong to large publicly-traded multinationals. If the margin achieved in a specific country does not reach a certain threshold, such companies may decide to stop marketing their products.

As a result, we will witness supply shortages. Indeed, we already have this issue with a number of specific illnesses in Switzerland, where manufacturing costs are considered too high. If the Federal Office of Public Health asks for prices which are lower than the manufacturing costs, such products will disappear from the market, leading to a risk of

their families, doctors, pharmacists, sickness funds and ultimately also the medically insured 6. Foreign price comparisons are not meaningful, as care systems in European comparative countries are different.

7. Comprehensive measures have to be taken to promote Generics including training and demand-side activities and information campaigns. Annual savings of 1 billion Swiss Francs directly and indirectly caused by Generics could be further enhanced 8. Prices of Generics have dropped significantly over the last 5 years alleviating the health care costs.

9. With medicine prices partially already below manufacturing costs attractiveness for manufacturer is decreasing.

Ongoing price pressure is endangering security of supply 10. We advocate freedom of choice of medicines.

Generics in Switzerland Still room for further growth Compared with other European and OECD countries the Swiss generics market is still not fully developed and lagging behind in terms of market share and penetration. Swiss Generics Association Intergenerika advocates improved incentives for pharmacists, doctors and patients to actively promote the cost-saving off-patent highquality pharmaceuticals.

Axel Müller has dealt with medicines during his entire life and holds a PhD in pharmacology. He has worked most of his professional career in the generics industry – from the API level, to the development and marketing of drugs. As MD of Intergenerika he actively promote generics in Switzerland as the drugs of first choice.

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Plotting Efficient C Paths for Clinical Development Clinical development is a complex puzzle, with elements such as geography, regulatory requirements, epidemiology, technology and expertise all contributing to successfully bringing a product to market.

Development of TLC388 in Asia for the treatment of liver cancer illustrates geographic advantages in accelerating global clinical development.

George Yeh, President, TLC, Taiwan

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linical development is a complex puzzle, with regulatory requirements, epidemiology, technology and specific clinical expertise all involved in how efficiently a product is developed and ultimately brought to market. Many elements of this puzzle are closely related to geography and vary from one region to another. As a result, thoughtfully considering the role of geographic region in development strategy pays off in bringing a therapy through development to prepare for approval.

Epidemiology

Geographic variation in disease prevalence affects clinical development strategy in subtle ways. Regulators are more engaged with development teams addressing areas of clear need – which can involve indications that are very common but lacking

Strategy

satisfactory therapeutics as well as indications that are relatively rare. For example, liver cancer is a leading cause of cancer deaths across Asia, with no effective treatment currently available.

This high need makes the prospect of an accelerated development pathway more likely in this region.

Of the 780,000 new cases of liver cancer diagnosed worldwide every year, half are in mainland China. When developing a new drug in oncology, TLC388, Phase 1 data supported the potential for multiple indications. Based on business considerations, we chose to first evaluate this drug in liver cancer.

The result is that TLC388 has been accepted into the accelerated ‘Green Path’ regulatory review procedure in mainland China. Because liver cancer is a rare disease in Western countries, TLC388 was able to obtain orphan drug designations in both the US and in Europe. Orphan drug status will not only help to accelerate development, but can also lead to market exclusivity of seven and ten years, respectively, in these markets. Following a successful Phase 1 trial at sites in the US and Taiwan, we are now conducting a Phase 2 study investigating the efficacy of TLC388 in liver cancer at sites in Taiwan and mainland China.

The prevalence of liver cancer in Asian populations also makes it easier to focus on a narrow subset of patients within this indication and still address a substantial need. For TLC388, we are first looking to determine efficacy as a second-line treatment in patients

To find an efficient development path, drug developers should carefully consider how factors related to geography relate to each attribute of a particular new therapeutic.

and a second trial directed at a larger, more broadly distributed, patient population to help with the speed of enrolment is a development strategy that captures the best of both worlds in disease epidemiology. Our second planned trial for TLC388 reflects this strategy. This trial looks to address an indication that is prevalent worldwide, colorectal cancer. Colorectal cancer is the third most common cancer globally, with over 1.3 million new cases estimated in 2012. Countries with the highest incidence rates include Australia, New Zealand, Canada and the United States.

Culture

at advanced stages of disease, where patient survival is typically less than three months. The Phase 2 trial investigates treatment for a subset of patients with portal vein tumour thrombosis, which makes up about 35 to 40 percent of all liver cancer patients. Data from a pilot study with TLC388 demonstrated the potential for TLC388 to expand treatment options for these patients–specifically, creating the opportunity to consider a minimally invasive procedure called Trans Arterial Chemo Embolization (TACE) that can be used following a sufficient amount of tumour shrinkage and reduced blockage of the portal vein.

Aiming for one trial to be conducted quickly in a specific patient subgroup

While disease prevalence is one potential factor that contributes to the efficiency of enrolment, another factor related to geography is the presence of an established clinical research culture.

This culture is associated with welldeveloped healthcare systems that help ensure that a trial is conducted according to accepted global standards. Also, patients’ trust in the healthcare system is reflected in high rates of participation in clinical trials and low drop-out rates. Several regions in Asia are notable for cultural factors that lead to a good track record of clinical development, notably Taiwan, as well as South Korea, Singapore and Hong Kong.

Regulatory priorities

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developers interested in the mainland China market may take advantage of the mutual recognition mechanism between Chinese and Taiwanese regulators. By conducting early stage clinical trials in Taiwan, developers benefit from clinical expertise with exploratory clinical trials. By conducting larger Phase 2 trials in China, developers benefit from the larger pool of patients. In the case of TLC388, we were able to move straight into Phase 2 trials using data from the Phase 1 study conducted in Taiwan, without having to reproduce safety studies in China. This has reduced development time considerably.

Technology platform

The specific class of technology is also relevant to the choice of where to develop a particular type of therapy.

A product applying a new delivery technology, for example, can often make use of the 505(b)(2) pathway in the US, which is a tried-and-true

path for accelerated development. In mainland China, recent reforms provide similar benefits for new formulations by increasing the priority of these drugs in the process of regulatory review. These reforms echo a trend in the emergence of new formulation drugs as away to create improved therapeutics. These policies may reflect that incremental improvements to existing drugs through new formulations can help to satisfy unmet market needs in a more timely and lower-risk manner in comparison to developing drugs from scratch.

Keeping current with policies and trends related to particular technologies is critical for seizing opportunities as they arise.

Another example of the potential relevance of a technology platform in the choice of development region could be regenerative medicine therapies using stem cell technology. Countries like Australia and Japan may be more receptive to these approaches from

regulatory or cultural acceptance perspectives. Developers with stemcell-based platforms may choose to prioritise these countries for clinical development.

Regional expertise

Clinical expertise also varies by geography and can be a significant factor in the efficiency of a clinical development program. By choosing sites with clinical investigators who have specific experience with previous studies for a particular indication, developers can avoid potentially serious difficulties in trial execution. For our new osteoarthritis therapy designed for sustained effect, we included Australian trial sites in our Phase 2 plan because these sites had experience conducting trials for osteoarthritis with similar endpoints and design.

To find an efficient development path, drug developers should carefully consider how factors related to geography relate to each attribute of a particular new therapeutic. What matters most to regulators in different regions? How will disease prevalence influence patient recruitment, create opportunities for specific indications and affect future markets? What kinds of technology are favoured? The answers are rarely immediately evident. However, by carefully matching a therapeutic candidate to features of the global development landscape, developers can more efficiently navigate the path of clinical development.

A u t h o r BIO President of TLC since 2002, George Yeh has extensive experience in finance and strategic planning for start-ups based in the US and Asia.

Mr. Yeh previously served as chief financial officer at Hermes Biosciences and received an MBA from the University of Michigan at Ann Arbor.

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Strategy

Trends in Pharma Export Industry in India The Indian pharmaceuticals market has become the largest exporter of medicines by volume. India is the largest provider of generic drugs globally with the Indian generics accounting for 20 per cent of global exports in terms of volume. In terms of market size, the Indian pharma industry, which is expected to grow over 15 per cent per annum between 2015 and 2020, will outperform the global pharma industry, which is set to grow at an annual rate of 5 per cent between the same period. The market is expected to grow to US$55 billion by 2020, thereby emerging as the sixth largest pharmaceutical market globally by its size.

Piyush Gupta, Associate Director, GNH India

W

hile talking about the beginning of Indian pharmaceutical industry, it begun in the late 50s and early 60s, out of the need to meet local shortages and bring down the cost. At that time, most medicines were imported into India and market was dominated

by MNCs. Once domestic market was conquered by local companies, there was a need to spread their wings in international market in late 80s and early 90s. By late 2000, over 50 per cent revenue for major Indian manufacturers was from International markets.

Looking at the early years, the Indian pharmaceutical industry 20

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Strategy

in 1950s had limited resource and opportunities, with few technological capabilities to manufacture modern drugs, locally. In order to tackle this situation and overcome the challenges, Indian entrepreneurs received an enormous support from the government to fill this void in the pharmaceutical industry. As a result, pharmaceutical industry in India turned to a mass production of generics of every imaginable nature.

The pharma industry in India emerged as the most dynamic technological content segment in the Indian manufacturing in the 1990s. In the span of three decades from the 1950s through the 1970s, the Indian pharmaceutical industry has grown from its formerly meager existence, with a low

production base, heavy dependence on imports, domination by foreign firms and high prices of drugs, to being one of the largest pharmaceutical industries in the world.

Indian pharmaceutical industry at present

Over the years in this journey from 1950s to 2010 Indian pharmaceutical industry has added several feathers to its growth crown (see figure 1).

In this period, the Indian pharmaceuticals market has become the largest exporter of medicines by volume. India is the largest provider of generic drugs globally with the Indian generics accounting for 20 per cent of global exports in terms of volume. In terms of market size, the Indian pharma

industry, which is expected to grow over 15 per cent per annum between 2015 and 2020, will outperform the global pharma industry, which is set to grow at an annual rate of 5 per cent between the same period. The market is expected to grow to US$55 billion by 2020, thereby emerging as the sixth largest pharmaceutical market globally by its size.

Also, the world’s largest number of US Food and Drug Administration (USFDA) approved factories outside the USA are located in India. Overall drug approvals given by the USFDA to Indian companies have nearly doubled to 201 in FY 2015-16 from 109 in FY 2014-15 (see figure 2).

With any success also come challenges and setbacks, as today, Indian

Figure 1 www.pharmafocusasia.com

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Strategy

pharma industry is well established and present in all global markets.

Current Challenges Regulations

Keeping in mind the sheer number of SRA (Stringent Regulatory Authority) approved facilities in India, the pharma industry is bound to become the centre of attention by many authorities. Currently, there is a fierce increase in the number of companies receiving a notice or warning letters (see figure 3).

There’s no simple solution to this, but following are some points that can bring these incidents down: a. Training local regulatory inspectors to perform inspections of international levels. This way many deficiencies can be identified and addressed locally, without it be-coming a Global News ‘Item’. b. The Local Regulatory body i.e.

CDSCO and State FDA needs to get Accredited by WHO and India should join PICs, this will automatically raise the bar of local regulators. We cannot expect our companies and facilities to be world class while our regulators are way behind. c. Proactive quality approach - while many pharma companies in India are already working in this direction, the challenge is to get the industry thinking on these

Figure 2

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In order to strengthen the ties of the pharma industry, we need a national policy on pharmaceuticals and government’s intervention is the areas needed

lines, as well. International requirements of ADR, Pharmacovigilance etc. should be made mandatory for domestic markets, too. At present, 80 per cent pharma companies maintain this infrastructure for international markets. Making it mandatory for domestic market as well will increase the quality perception of Indian market in International arena.

Product quality

Today, one of the biggest concerns of International clients, regulators and agencies is quality of Indian medicines.

Internationally, India’s generic medicine industry has been questioned for compromising on product quality. The Indian pharmaceutical industry is the largest supplier of cost-effective generic medicines to the developed world. With the widest range of medicines available for exports and with the availability of the largest number of approved pharmaceutical manufacturing facilities, India is all set to become the leader of pharmaceutical exports to the world.

Until product quality control is not introduced in the domestic market, India’s international image will not improve. The country’s medicine industry has to put its house in order and the government should monitor it stringently.

A considerable amount of domestically available (medicines meant for Indian market) get exported to other countries from India. According to IBEF, the domestic Indian pharmaceutical industry is estimated to be US$26 billion in 2014 growing at nearly 20 percent and is expected to reach nearly US$50 billion in 2020.

As compared to international markets, quality requirements for domestic markets are pretty lax, but when the similar medicine stock is exported, Indian image takes a beating. In short, the quality parameters for international markets and domestic market should be bought on par. Once, the effective quality check and control system is set for domestic market, it can automatically reflect internationally.

Biosimilars

Biosimilars were envisaged as the ‘Next Frontier’ the next ‘Engine of Growth’ but sadly almost all biosimilars approved in India are facing a challenge in court by innovators.

Our domestic home grown pharma companies are in a race to be the ‘First’ in the market, disregarding the basic principle of biosimilar i.e. similars are not exact copy like a synthetic generic molecule, and further push our regulators to approve these formulations without adequate supporting documents.

The right way for Bio Similar development should be followed i.e. it should be similar in therapeutic effect but not exact copy of the molecular structure, and demonstrable QSE profile and adequate multi-centric trials. If we get the biosimilar equation right, it will be the next growth engine for the industry.

Quality lapses and human resource in pharma industry:

With the Indian pharma industry’s personnel turnover at 33 per cent, every three years, there is a completely new staff in a company. The attrition rate in the pharma industry is extremely high.

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Strategy

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intervention and until the employees start sticking around for a min of 8 to 10 years, it is impossible to achieve lasting success in this field.

Inflexion point and role of government

In early 2000, the Indian pharma industry was climbing the growth ladder with increasing USFDA approval, and rising stocks of pharma companies. And now it’s time for USFDA to conduct follow up inspections.

Today, in the given situation, the future of the industry depends on how we react and address today’s challenges.

In order to strengthen the ties of the

A u t h o r BIO

Pharma is one of the world’s most paperwork-intensive industries. It is also one of the world’s most scrutinised industries. It is a very people-sensitive industry, wherein a well-being and health of a human being matters a lot.

So how does a company maintain quality in the absence of skilled staff? In my experience of having worked in the industry for 15 years, I have noticed a general lack of responsibility amongst people. They don’t want to take responsibility for their actions.

To train a single person on good manufacturing practices for pharmaceutical products - GMP principles takes one year and cost over Rupees 5,00,000in training costs. This trained person can only start contributing positively by the 2nd year and by this point he is already looking for another job in the market.

If we intent to pay attention to quality, this is impossible until the brain drain in the industry is not addressed.

In the pharma industry, quality work cannot be automated, it needs manual

pharma industry, we need a national policy on pharmaceuticals and government’s intervention is the areas needed.

In this case, on the other hand, distracting pharma companies with DPCP, NDPO etc… are not the solution.

The government should become the facilitator in the industry, get our local regulators accredited and lay the foundation for industry to prosper.

With these changes, we are certain that the international inspections will reduce by over 90 per cent if our national regular is WHO accredited and we are members of Pharmaceutical Inspection Co-operation Scheme (PICS).

Gupta is the Associate Director at GNH India and is responsible in leading the business development effort in global markets for Clinical trial supplies, International Tenders, Orphan drug supplies and vaccines. He is a Council Member at GLG (Gerson Lehman Group) USA for their healthcare practice and advices investment bankers on Indian markets for the group.

RESEARCH & DEVELOPMENT

Biologics and Biosimilars Promising field for medicines for the future

With the early generation of biologics starting to lose patent protection, the field of biosimilars too has been gaining attention. Biosimilars are the generic version of a biologic drug developed for launch post the patent expiry of the original drug.

While it is relatively very easy to develop the generic versions of small molecules, it is extremely complicated to develop biosimilars due to the technical challenges associated with biologics. There has been considerable interest in biosimilars in developing countries due to the needs of the local population for affordable medicines as well as the pharmaceutical manufacturing experience available locally.

Dhananjay Patankar, Head, Pharmaceutical and Biopharmaceutical Development, Syngene International Ltd., India

U

p until a few years ago, the field of medicine was largely dominated by small molecules or pharmaceuticals as they are more commonly known. Large molecules, or biologics, were relatively less heard of and there were very few players operating globally in

this area. Over the past two decades, the biotechnology industry has come a long way. According to a report prepared by the Department of Industrial Promotion and Policy (DIPP), Government of India, the global biologics market is expected to be around US$290 billion by 2020

accounting for an estimated 27 per cent of total pharma sales.

Biologics are a particular genre of drugs whose active ingredients are sourced from living organisms that have been specifically modified to produce the desired molecules. Unlike small molecules, which are usually produced by chemical synthesis, biologic drugs are giant molecules, typically proteins, which are hundreds of times the size of a conventional drug molecule. Such large proteins cannot be manufactured through chemical synthesis, but are produced inside animal cells or micro-organisms such as bacteria and viruses cultivated in large fermenters, or sometimes even in specially modified (or ‘genetically engineered’) plants or animals (and extracted from the leaves of the plant or milk of the animal).

The first generation of biologic drugs, such as insulin or growth hormone, were natural proteins produced through large-scale production techniques, and mostly used as replacement therapies for patients suffering from deficiency. In newer www.pharmafocusasia.com

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for seven of the ten bestselling drugs in 2013. Morningstar, an investmentresearch firm, estimates that biologics will contribute 32 per cent of the big pharma companies’ sales by 2023.

Multidimensional alliances, where large multinational corporations partner with research organisations, or biopharma companies collaborate with biotechnology institutions, have proven to be very successful. Such alliances seem to have become the model for this industry and these alliances are also constantly adapting to their dynamic environment. In this scenario, it is necessary for pharmaceutical companies to network more, become global and commercial, and abide by regulations that support an environment of innovation.

With the early generation of biologics starting to lose patent protection, the field of biosimilars too has been gaining attention. Biosimilars are the generic version of a biologic drug developed for launch post the patent expiry of the original drug. According to a Grant Thornton report on biosimilars, twenty one biologics, with a market value of about $54 billion, will be losing patent protection by 2019 in the US alone.

The DIPP report estimates that biosimilars will account for about US$25-35 billion of the total biologics market by 2020.

While it is relatively very easy to develop the generic versions of small molecules, it is extremely complicated to develop biosimilars due to the technical challenges associated with biologics.

Moreover, since biologics are made in living organisms, it's difficult to make

A u t h o r BIO

drugs, natural proteins are altered, by a process known as protein engineering, to perform specific tasks. The key advantage of biologics over small molecules is that they mimic the normal complex function(s) of proteins within the body, which often cannot be replicated by a small molecule, inherently foreign to the body.

While the advantages of biologics are known, there are some challenges too. The molecules are complex and delicate, and require careful handling.

Sometimes a modification in one corner of such a large molecule may be difficult to detect by analytical techniques but may have significant impact on its function. Protein drugs are difficult to take as well. They must be injected, infused or inhaled, as they are destroyed in the stomach when swallowed.

The key step in the production of a biologic drug is to create a ‘genetically engineered’ animal cell or microorganism (or in some cases plant or animal), i.e. one whose genetic code has been modified to produce the desired protein.

The overall drug development pathway for biologics remains the same as small molecules, starting with identifying the target, validating the information, screening and testing, followed by pre-clinical and clinical trials before its commercial approval.

Newer generations of biologic drugs have started delivering cures, by using viruses to deliver ‘gene therapy’—the replacement of a faulty gene in a patient’s body cells with the correct version or a specially designed version.

Biologics have thus revolutionised the treatment of complex diseases such as cancer and rheumatoid arthritis.

However, because of the technical challenges referred above, biologic drugs are often more expensive to produce than small molecules.

Modern protein-based drugs have become a major force in the pharmaceutical industry. According to a report by Visiongain, up to a third of new drug approvals in developed markets have been for biologics and they accounted

an exact replica of the product and the biosimilar product may either be better or significantly worse than the original. Earlier it was believed that it was impossible to develop a biosimilar that is equivalent to the original molecule in all respects; however with the advancement in the field of process technologies and analytical technologies, developing products matching with the original drug in structure as well as clinical function is possible. A number of biosimilars have now been approved the world over.

There has been considerable interest in biosimilars in developing countries due to the needs of the local population for affordable medicines as well as the pharmaceutical manufacturing experience available locally. As per Make in India campaign by the government, Indian biotech industry, comprising bio pharmaceuticals, is expected to grow at a rate of 30 per cent a year and reach US$100 billion by 2025. A new biosimilars policy called the ‘Guidelines on similar biologics’ prepared by the Central Drugs Standard Control Organization (CSDCO) announced by the Indian Government is expected to give a major boost to the Indian biologics and biosimilars industry making it more competitive in the global arena.

The previous century was the century of small molecules. While these small molecules will continue to be a key element of the global pharmaceuticals industry, the current century is more likely to be the century of the large molecules or biologics, promising better treatment to millions of people.

Dhananjay holds a Ph.D from the University of Utah, USA and a Post-Doctoral Fellowship from the Rutgers University, USA and has done his Master’s degree in Chemical Engineering from the Indian Institute of Technology, Mumbai. He has over 20 years of professional experience and has been a leader in the Indian biopharmaceutical industry. He has been serving on Expert Committees with the US Pharmacopeia for the last 5 years. Prior to joining Syngene in 2010, Dhananjay worked with Intas Biopharmaceuticals as Chief Operating Officer where he led the development and commercial manufacturing operations of several biologics for the global markets.

RESEARCH & DEVELOPMENT

Wearable Large Volume Drug Delivery Devices Hold key to pharmaceutical lifecycle management, patient preference 28

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RESEARCH & DEVELOPMENT

Pharmaceutical companies racing to develop promising new biologic treatments are embracing disruptive drug delivery technology.

Patient-friendly wearable large volume injectors from Enable Injections make at home delivery of large volume (5-50ml), viscous drugs easy, comfortable and convenient, promoting compliance. They can differentiate products, extend product life cycles and impact treatment outcomes positively.

Michael D Hooven, President and CEO Enable Injections Inc., USA

I

t costs approximately US$2.6 billion (17,904,380,000 yuan) to bring a single new drug to market-and the cost, as well as the hurdles to innovation, are getting higher. Yet innovation is crucial to the pharmaceutical industry, and the need for a strong product pipeline is sending companies racing to develop some of the most promising new treatments—biologics-in the hope of developing another blockbuster drug likeHumira, AbbVie’s biologic treatment for rheumatoid arthritis and related diseases.

Humira sales topped US$14 billion in 2015, and AbbVie raised its earnings forecast for 2016. Another 39 biologics also reached blockbuster status last year, exceeding US$1 billion in sales. Nine of these biologics brought in US$5 billion in global sales. Biologics continue to be the main drivers of industry growth and are predicted to reach US$445 billion in sales by 2019, up from US$289 billion from 2014.

However, a Deloitte 2016 pharmaceutical industry report1 states that while drugs will remain important, they will represent a diminishing share of what comes together to deliver an overall www.pharmafocusasia.com

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and comfortably be self-administered by the patient at home, at work or in transit in just a few minutes. There is no needle in sight and the patient, no longer tethered to an IV line, is free to ambulate during treatment, making the experience far less stressful.

These innovative drug / drug delivery partnerships help assure that once the new drug/device combinations reach the market, their value proposition is realised as the result of improved compliance, a requisite for improved outcomes. In large markets like the US, reimbursement is soon to be determined by outcomes, making effective new technologies that boost compliance imperative.

Remove complexity to boost compliance

outcome. For pharmaceutical companies this emerging trend means growth will depend on innovation beyond just finding new drug candidates.

Luckily, disruptive innovation that can positively impact outcomes, create patient preference and lower drug development costs has arrived in the form of wearable large volume subcutaneous injection technology that makes it easy for patients to self-administer doses as large as 5mL to 50 mL at home with minimal if any discomfort.

A second trend, patient centricity, has long been embraced by pharmaceutical companies. Industry leaders Roche/ Genentech and Novartis, for example, have produced some of the most successful products of the last decade—Avastin, Rituxan, Herceptin, and Gleevec. To what do these drugs owe much of their product leadership? To the companies’ focus on the continual drive to improve the patient experience.

Nowhere is disruptive drug delivery innovation to enhance the patient experience more critical than with the large volume, viscous biologics that now comprise more than 50 per cent of products in pharmaceutical devel30

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opment. For these drugs, subcutaneous delivery has been a major goal and chronic challenge—until now.

Now pharmaceutical companies can seize the opportunity to be in the forefront of both trends by marrying their large molecule drug products to revolutionary patient-centric drug delivery— and reap the benefits, just as Alibaba and Amazon have done by revolutionising shopping.

Amazon, Alibaba and many others offer home delivery. It’s popular. It’s convenient. With use of the new wearable drug delivery technology, pharmaceutical companies can also offer patients home delivery, although of a slightly different nature but equally desirable – the ability to skip the trip to the hospital for an infusion and instead easily self-inject biologics, with minimal or no pain, in the comfort of their own homes using the newly available more advanced high volume injectors like those from Enable Injections. For example, a patient requiring an infusion for treatment of an autoimmune disorder must travel to a health facility for a 30 to 90 minute IV infusion. Using a wearable large volume injector instead, the same dose can easily

The medical literature leaves little doubt that taking medication as prescribed and for the recommended time period is problematic for many patients and can significantly impact healthcare outcomes and cost of care. A World Health Organization (WHO) report cites non-adherence as a leading cause of preventable morbidity, mortality and cost.

Yet compliance among chronic disease patients averages just 50 per cent.

The WHO report cites complexity among the major causes of failure to comply with prescribed medication.

Reducing this complexity and its associated cost is another major challenge facing the pharmaceutical and biotech companies developing the biologics, monoclonal antibodies and immunoglobulins that are transforming treatment of cancers and chronic diseases.

The most advanced wearable large volume injectors, such as the Enable Injector, are designed to eliminate complexity, potentially helping create tomorrow’s blockbusters. Patient confusion and error are minimised by requiring only a few simple steps: • INSERT a standard drug vial/syringe/ cartridge into the transfer system, which automatically warms any refrigerated product in the 30-40 seconds

RESEARCH & DEVELOPMENT

it takes to fill the on- body delivery system • PLACE the injector on skin • PULL the safety tab • PRESS one button.

New wearables extend product lifecycles

Biologics hold great promise for treating a multitude of illnesses. Cancers and related conditions are the most researched area for biologics, according to analysts.

Other prominent target diseases are autoimmune diseases, blood disorders and genetic disorders. The list includes, but is not limited to: • Numerous cancers • Rheumatoid Arthritis • Multiple Sclerosis • Hemophilia • Myasthenia gravis • Lupus • Vasculitis • Sickle cell anemia • Crohn’s Disease, ulcerative colitis and other digestive disorders • Duchenne muscular dystrophy, Pompe disease and other genetic diseases • Infectious diseases such as HIV, Ebola and CMV diseases • Transplantation • Inflammatory diseases

• • • • • •

Cardiovascular diseases Respiratory diseases Musculoskeletal disorders Eye diseases Skin diseases Neurologic disorders.

Improving the patient experience rewards pharmas

Already, 11 established biologic products – representing 48per cent of total biologic sales –are slated to lose patent protection by 2022. Companies with biologics on the market can take advantage of the new drug delivery technology to plan their patent extension strategies—and at the same time enter the next frontier in vastly improving the patient experience, creating preference. They can also use the technology to differentiate their emerging or young commercial products.

But biologics development creates challenges, and again the new wearable technology can be of assistance.

Wearables technology speeds development, formulation

Why change the way pharmas create and administer drugs? Because the need to reduce costs, increase efficiency and maintain margins is increasing pressure on pharmaceutical executives to be more

creative. Ultimately, changes are likely to pay off. From the drug development point-of-view, the new delivery technology can cut costs and speed time to market.

Here’s why. Most biologics consist of mega-molecules that are hundreds of times the size of conventional small molecule drugs. Biologics are frequently composed of a heterogeneous mixture of more than 1,300 weighty amino acids.

That creates three main challenges for pharmaceutical companies seeking to develop the next blockbuster biologic: 1.They are hard to make 2.They are hard to take 3.They can be expensive Despite these difficulties, targeted as they are to particular genes or proteins, biologics are compelling for treating diseases due to their higher specificity and fewer side effects.

Scientists developing biotherapeutics spend enormous time and effort on formulation–sometimes years. This amount of time and effort can be significantly reduced by the newest biologics delivery technology.

The wearable large volume injectors bring to market a novel product development aid that reduces formulation time and effort by enabling a simpler method

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RESEARCH & DEVELOPMENT

For patients, biologics are now easy to take

Subcutaneous injection remains the preferred method of delivering injectable drugs, including biologics. Yet historically injectable drug administration has been particularly problematic, in large part because most patients dislike injections, especially those that are selfadministered. Injecting biologics would be even more painful and difficult for patients due to the large doses required and their viscosity. Syringes and earlier large volume injectors cannot handle anywhere near doses of up to 50 mL or their viscous formulations.

But now such large doses are possible for patients to self-inject easily and 32

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comfortably. Today’s wearable high volume injectors offer safety, ease of use, and injection comfort-vital attributes if uncomplicated self-injection of biologics is to gain traction. The new delivery technology is also connected and can monitor compliance, potentially a major step in improving data collection to assess and enable HCP intervention to help improve, treatment outcomes.

Fulfilling the vision of self-injection that is safe, easy, comfortable and convenient for patients, yet cost effectiveness for the pharmaceutical industry and payers, today’s most sophisticated drug delivery devices are distinguished by the following: • Use standard vials, syringes or cartridges so no change to the primary container is required. This eliminates additional time-consuming and expensive stability studies • Automatically warm the drug as the injector fills, reducing the typical 30-minute or longer wait time to use a refrigerated drug to seconds • For lyophilized drugs, completely automate mixing and reconstitution, removing any patient variability from the mixing process • Use only standard intravenous-set materials in the drug delivery path, minimising short-term material-drug compatibility issues • Use a small needle size to optimise injection comfort • Very small in size with a low profile that can discretely be worn on the body, eliminating the problems and inconvenience associated with carrying larger, heavier devices while ambulating

A u t h o r BIO

of product preparation. Formulation teams can take advantage of the innovative delivery technology to speed development of stable, bioavailable, clinically relevant formulations.

Formulation teams can also facilitate patient self-injection of biologics by adopting drug delivery technology that aids in: • Delivering more volume of product • Delivering much higher viscosities caused by higher concentration of proteins • Resolving biologics’ greater propensity to precipitate out of solution.

The time and effort savings are accomplished with automated processes performed by the Enable Injector that accelerate or eliminates tedious, time-consuming formulation functions for more rapid-and less costlyproduct development. In addition, the requirement for formulation teams to concentrate the product in the smallest possible dose for delivery by an autoinjector (typically <1ml) may no longer be relevant. The latest generation of injectors has the ability to provide a comfortable injection experience for higher volume product delivery. Patient acceptance of new higher volume on-body delivery systems should be high since the devices support mobility, are easy to use and minimise any injection discomfort.

• Environmentally friendly – no electronics or batteries to remove or recycle • Total volume of materials and packing less than that for a standard IV set • Enable subcutaneous injection up to 50 mL • Customisable drug delivery rate, duration, volume and needle size for creation of a much improved patient injection experience • Apps-based connectivity.

Will these factors boost compliance?

Overall drug regimen compliance has historically been low, and any improvement would benefit both patients and drug makers. It remains to be seen to what extent the ease and convenience of using biologic/device combinations will impact compliance, improve outcomes and reduce drug wastage. Their connectivity will be helpful in that assessment.

It looks promising. Among the key attractions of the newest on-body delivery systems: with never a needle in sight, patients like using them, removing the many barriers to compliance that have vexed the industry for decades.

Summary: to profit, partner

The new, most advanced wearable large volume injectors available now for clinical trials and commercial application are designed to address the challenges of formulating biologics, delivery complexity, patient compliance and cost.

Biologics/patient-centric delivery device partnerships are key to pharmaceutical product lifecycle management and brand preference.

References available at www.pharmafocusasia.com

Michael D Hooven is President and CEO, Enable Injections, Inc. He has over 30 years of experience in the medical device industry in a broad variety of business, technical, and clinical areas. He is the Founder of five medical device companies and holds over 100 issued and pending US patents. He is the Founder and a Director of AtriCure, Inc. where he previously held positions as the Chairman and CEO. He is also Founder and Chairman of Enable Medical, a surgical device manufacturer that was acquired by AtriCure in August of 2005.

Cover Story

Patient Recruitment An industry challenge

To address the challenges faced in patient recruitment and retention in clinical trials, innovative technologies are being utilised in Asia-Pacific as well as other regions to optimise the processes involved. From patient matching to improving the consent process, technology has the power to help Biopharma organisations in Asia Pacific transform clinical development.

Mary Pan, VP, Asia Pacific, ICON plc., Japan

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atient recruitment and retention is frequently the most laborintensive and difficult part of the clinical trial process and is often a barrier to the successful completion of a study. Industry data indicates that patient recruitment can represent more than 30 per cent of total study costs and sponsors bear a tremendous cost when ambitious recruitment goals, often misguided, fall short. Asia-Pacific is one of the most successful regions in terms of the speed at which study sites complete the start-up

clinical trails

process and begin recruiting patients. It is also the top region in terms of achieving target enrolment levels. However, because it comprises a large number of culturally diverse countries, patient recruitment and retention strategies, there is a need to be more targeted and tailored to individual countries than is required in other regions. In recent years, a number of technology innovations, such as eConsent and patient portals, have been adopted by pharmaceutical companies and CROs to aid this process.

However, the extent to which different technologies are utilised varies between North America, Europe, and Asia-Pacific.

This article reviews some of the patient recruitment and retention technologies and how some of that technology is applied in Asia-Pacific.

Finding the right sites and patients for the right trial

Recent technological developments have shown how technology platforms and cognitive computing power is helping automate the cumbersome process of identifying patients who meet the criteria for a clinical trial, and how these can be used to analyse protocols to assess trial feasibility. This is allowing better access to patient populations and the increased information available enables site and patient recruitment to be optimised, with improved matching of patients for clinical trial participation. Clinical and laboratory data from Electronic Medical Records (EMR) can also identify suitable investigators and patients.

Patient profiling is used to create a profile of the typical patient for each trial, which helps to target the correct patients. Technology solutions, such as using patient registries and online forums, are also playing a part in the transformation of this area by being used to directly recruit patients and improve patient retention by providing an additional communication channel to standard doctors’ appointments.

One important technologic advance that is being used in Asia-Pacific as well as other regions is the cognitive comput-

The challenge in Asia-Pacific is not the implementation of technology but rather its commercialisation.

ing power of IBM’s Watson. Watson is the first commercially available cognitive computing capability representing a new era in computing. The system, delivered through a cloud, analyses high volumes of data, understands complex questions posed in natural language, and proposes evidence-based answers.

Watson continuously learns, gaining in value and knowledge over time, from previous interactions and can be used to help automate the cumbersome process of identifying patients who meet the criteria for a clinical trial and to analyse protocols to assess trial feasibility and identify optimal trial sites. It can rapidly identify how many patients match a clinical trial’s inclusion criteria, where the patients are located and how they will be recruited. The Watson Health Cloud facilitates access to anonymised patient data by enabling the massive amount of personal health data being created daily to be anonymised, shared, and combined with a dynamic and constantly growing aggregated view of clinical, research, and social health data. IBM has opened a new research centre in Singapore this year and it aims to expand its offering into Asia, with healthcare being one of the focus areas.

Patient-centric technology

Using a web-based patient portal enables more patients to easily find a suitable clinical trial available for their therapeutic area, clinical trial information on patient criteria suitable for those trials, and is

also specifically designed to enhance a patient’s understanding of a study before consenting to participate at an investigator site. A patient portal ensures that they have ample time to review consent materials, and prepare any questions before the face-to-face meeting with the investigator. Improved patient education leads to a more informed consent process which not only has the potential to increase patient recruitment but also increase the likelihood of the patient staying on the trial, because they know what to expect. Portals can also enable pre-screening questionnaires and selection of a convenient study location, all designed to make it easier for the patient to participate in the right trial. Other features include enabling investigators to engage directly with a patient who has expressed interest in participating in a trial at their site, schedule visits, and examine live analytics about the materials the patient has reviewed. Research has shown that patients prefer to learn about the trial through the more accessible medium of video and the information provided in this format is more easily understood as it transcends language barriers and provides consistency across sites.

A truly informed consent process

The informed consent process is a prerequisite for patients’ participation in clinical trials, but difficulties can occur when the expectation is for patients to read and understand informed consent information, which typically can consist of documents containing more than 20 pages. These documents are essential to properly convey the trial activities and procedures, but are often full of complicated medical terminology that can be difficult for patients to comprehend. In addition, the increasing complexity of many clinical trials and trial protocols means that more time is required to complete the consent process, which in turn leads to greater costs.

Using electronic consent (eConsent) helps to improve the consent process while reducing the time and www.pharmafocusasia.com

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cost of the consent process. Presenting information visually on a screen rather in a printed document can be much more easily understood and retained, helping patients to comprehend the information and, therefore, providing truly informed consent. For example, providing a 3D visualisation of how a drug works in the body is much easier to understand than reading a paragraph about a drug’s mechanism of action. Key information that influences a patient’s decision to participate in a trial can be provided in an interactive, engaging format, using a multimedia approach comprising elements such as video, text and graphics. eConsent enhances the patient consent process for not just patients, but also investigators, site staff and sponsors.

It effectively supports the investigator in communications with the patient and other study staff by providing more education and introducing more consistency and compliance in the trial.

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Asia-Pacific continues to have great recruitment potential for clinical trials, with its large and diverse patient populations and proficiency in achieving fast study start-ups and patient enrolment targets.

Improving patient recruitment and retention with wearables

The increasing popularity of fitness and wellness devices is well documented, with device manufacturers and technology giants creating a digital mobile health revolution in which individuals can now monitor different aspects of their health status, such as heart rate, sleep quality, and exercise rate, as part of their normal daily routine using wireless-enabled

wearable technology devices. But how can this technology be used to improve the clinical trial process and in particular to support better patient recruitment?

We now have the means to innovate the ‘where’ and the ‘how’ of patient data capture to create a 24-hour digital map of physical behaviours and quantifying daily life; but the use of sensors also has the potential to reduce the patient burden of having to travel, in some cases long distances, to a centralised site on a regular basis and instead create virtual sites in a patient’s home. Wearable technology devices, with their ability to collect and transmit physiological parameters, are a key component of decentralised data collection. They can be used not only to generate clinical data but are also valuable as screening and compliance tools. For example, specific sleep or activity patterns can be monitored where these form part of the study inclusion criteria or are a required component for the duration of the study. While the industry is still

Cecil Nick, UK

Edward Abrahams, USA

VP (Technical) at PAREXEL Consulting

President at Personalized Medicine Coalition

Javier Camposano, KR

Joanna Brougher, USA

Managing Director Drug Product Division at Celltrion Inc.

Owner & Principal, BioPhama Law Group, PLLC, Adjunct Lecturer, at Harvard School of Public Health

Paul H. Song, KR

Sarah Rickwood, UK

VP Business Development Team at Samsung Bioepis

VP, Thought Leadership at QuintilesIMS

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Cover Story learning about the value and practical use of wearables in clinical trials, its potential to support patient recruitment and retention is considerable.

Asia Pacific – varying degrees of implementation

The use of technology in patient recruitment and retention in Asia-Pacific is, in some respects, more advanced than in other regions, as governments embrace technology as a more efficient way to deal with the increasing burden of healthcare costs. For example, the Republic of Korea is the only country in the world that uses a single technology platform for the electronic medical records of the entire public health system. Japan uses just three platforms for electronic medical records compared with the many different platforms used in European countries and the hundreds of fragmented and unintegrated platforms used in the USA. The challenge in Asia-Pacific is not the implementation of technology but rather its commercialisation .

Much of the healthcare in Asia-Pacific is public and there are legal and regulatory barriers to the commercialisation of government-funded data for the benefit of private companies. An exception is India, where the majority of healthcare is private but highly fragmented and is, therefore, challenging to integrate nationally. In addition, because Asia-Pacific is a very culturally diverse region that comprises half the world’s population, a technology that might be useful for patient recruitment in one country or even a province may not be applicable in another country or province.

The Korean government established the Korea National Enterprise for Clinical Trials (KoNECT) in 2007 to encourage clinical research in the country. The services that KoNECT provides for foreign sponsors of clinical trials include a onestop shop giving comprehensive access to information about Korea, concierge services for smooth entry into the country, and business matching with selected local service providers. Asia-Pacific regional

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clinical trails

clinical trial networks and a national clinical trial integrated information system and database are being developed. KoNECT provides aggregated and analysed data directly from electronic medical records to support clinical trial patient recruitment.

Private for-profit patient recruitment companies also leverage technology. For example, the Japanese company CROee uses the clinical trial information website Seikatsu-Kojo WEB to help recruit patients. Patient information in Seikatsu-Kojo WEB is organised by different categories, such as disease, medication, and blood type, so the database can be searched to identify suitable candidates for a clinical trial according to various factors. Once identified, suitable potential candidates can be contacted in a number of ways, including uploading of study information to the website, direct

mail, and e-mail magazines. Members who are registered with Seikatsu-Kojo WEB are those that either want to take part in clinical trials or have expressed an interest in doing so.

Evolving to meet the challenges

Asia-Pacific continues to have great recruitment potential for clinical trials, with its large and diverse patient populations and proficiency in achieving fast study start-ups and patient enrolment targets. In some countries, such as Korea, there have been great strides to use innovative technologies and this trend is likely to continue into the future. As in other regions, technological advances are constantly being employed by pharmaceutical companies and CROs in Asia-Pacific to transform and improve clinical development including patient recruitment and retention.

A u t h o r BIO

Mary has over 16 years of experience in pharma, biotech, medical device and CRO industries.

She previously had responsibility for the development of a CRO from start-up to 150 employees. Mary’s prior experience includes business strategy and marketing for a significant medical device portfolio at Becton Dickinson and global drug development and medical affairs roles at Pfizer and Crucell (a J&J company). She holds an MBA (Brown University/IE Business School), an LLM in law (University of Edinburgh), an MA in International Relations (Freie Universität Berlin) and completed the MD Program in Liberal Medical Education (Brown University).

Clinical Trial Supply Southeast 2017 Cary is part of the Southeast’s Research Triangle Park, a growing and thriving community of over 80 biotech and life science companies. With such a booming community, Clinical Trial Supply Southeast gives local trial sponsors and vendors the opportunity to come together and discuss the latest trials and tribulations for the local industry.

Organised by

FREE

PLACES

reserved for VP/Director/ C-Level executive of Pharma/Biotech/Medical Device companies.

Key 2017 Speakers:

Key 2017 topics:

Leslie Holme, Supervisory Import Specialist, Pharmaceuticals – U.S. Customs and Border Protection Greg Hottell, Director, Supply Chain Group Lead – GSK Tim Holmes, Manager, Performance Operational Capabilities – Biogen Margaret Schubert, Sr. Investigational Product Specialist – Cato Research Mark Mann, Associate Director of clinical Outsourcing and Contracts – Upsher-Smith Lynne McKerlie, PhD, Lead Clinical Trial Materials Project Manager – Grifols Inc. Stephen Porter, CEO, President – VDDI Pharmaceuticals

Exploring import/export methods to ensure clinical supplies get through border control Analysing approaches towards forecasting and impacts on supply chain efficiency Insight into effective vendor management for clinical trial supplies Improving clinical study start up and lifetime operation by enhancing clinical supply team communication with clinical operations team Investigating best practices for obtaining patients to ensure you meet patient recruitment goals and avoid loss in revenue Overcoming challenges in managing overseas trials – steps for success in China

Join your peers at this year’s CTS Southeast conference to discuss the most pressing topics and explore opportunities in clinical supply, secure your place by quoting reference code: MK-ACAD For more information on the event, please visit:

www.arena-international.com/ctssoutheast

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Trends in Pharmaceutical Packaging and Delivery Throughout the world, the pharmaceutical companies and their packaging partners are adapting to new requirements and considerations to meet the needs of todayâ&#x20AC;&#x2122;s patients.

Much of their adaptation is focused on changes in packaging processes, including a focus on Quality by Design principles that will ensure enhanced outcomes for patients.

Troy Player, Vice President and Managing Director, Asia Pacific West Pharmaceutical Services, Inc., Singapore

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T

he global pharmaceutical market is evolving, driven by greater international regulatory requirements for improved quality as well as local healthcare policy such as the expansion of universal health coverage for China’s nearly 1.4 billion citizens launched in 2011-its annual spending projected to grow about 12 per cent in both 2017 and 2018, according to Deloitte research.

To meet the growing demand for medications and to deliver them in safe, patient-centric ways that meet the needs of the various populations they serve, pharmaceutical companies need packaging partners that offer a variety of systems to serve the healthcare systems of different Asia-Pacific locales.

For instance, diabetes treatment is on the rise in China thanks to universal health insurance, along with more widespread occurrence and timely diagnosis of the disease. That is driving the need for insulin in syringes, as care providers treat what the International Diabetes Federation terms “the world’s largest

The advent of biosimilars may open opportunities for increased access to biologics. This is a significant area of opportunity for many companies planning to enter the market with biosimilars versions of key drugs.

diabetes epidemic [that] continues to grow at a fearsome pace.”

As China works to curb diabetes -one in three of the world’s diabetics lives in China, with an astounding half a billion potentially with pre-diabetes elevated glucose levels-there may be a

call for auto-injectors and other more costly treatment medications and delivery systems in the future. But for the near term, the industry will continue to meet demand through traditional means.

Another example: In India, two spheres of drug development are emerging, each with their own set of standards.

Domestically, the emphasis is on generics and other cost-controlled medications to create affordable care for the highest number of people. For export, Indian manufacturers must adhere to quality standards that the destination countries mandate. As of today, roughly two-thirds of drugs manufactured in India are for export, and the industry as a whole continues to grow in capacity, year after year.

Traditionally, drug development may have started with the packaging system; however, it is increasingly important that companies ‘start with the end in mind.’ As an example, consideration of the final method of delivery and the patient population should drive

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container development. A drug designed for self-injection by an impaired patient, which requires a dosage of 2mL per month to provide optimum outcomes, may require a wearable injector incorporating a drug container capable of containing 2mL of liquid and delivering in a comfortable way over an extended period of time.

This drives the selection of a delivery technology, which in turn drives the selection of a drug container.

Medications to be delivered in hospitals often require consideration of other factors. For example, if the drug will be delivered by injection, how would the pharmaceutical company address increasing requirements for needle safety systems? If reconstitution or transfer is necessary, how can this be done effectively and quickly, while protecting the healthcare worker and patient alike?

Overall, the trends to watch in 2017 and beyond that will inform regional drug manufacture and the delivery systems that contain them are as follows: QbD Processes Help Meet Regulatory Mandates: Using Quality

by Design (QbD) provides a methodology for generating a deeper product and process understanding in the injectables market. Interest in QbD principles originated in the past decade out of regulatory pressures and the industry’s ongoing focus on quality and efficiency in drug manufacturing. Recently, QbD advanced through the entire supply chain with the understanding and requirement that all companies involved in the development, manufacturing, containment and delivery of drugs adopt QbD principles when bringing new products to market.

QbD principles can require a significant up-front investment, which can understandably lead some in the industry to initially shy away. That said, the investment delivers an improved, data-driven output that can lead to a superior product. Additionally, QbD initiatives also lead to a process that allow stakeholders to better understand risk and how to minimise it. APAC drug 42

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Focus on Caps and Seals: Across the globe, regulatory bodies are calling for higher standards for quality in pharmaceutical products and the packaging components and systems that contain them. One area of increased focus is caps and seals – components often used in the packaging of injectable drugs. In an effort to ensure consistent quality throughout a drug product’s lifecycle and mitigate potential risks to patient safety, pharmaceutical and biopharmaceutical companies are increasingly turning toward ready-to-sterilise and ready-to-use sterile packaging components and product qualities.

producers who export to Western countries will implement QbD techniques more frequently than for domestic drugs – but that will change as China has begun to change its approval system and other countries begin to examine new quality mandates.

More Stringent Local Regulations: In China, with the formal introduction and implementation of ‘quality management regulation of medical manufacture (revised in 2010)’, a series of standards related to sterile medicinal products has been put into practice. The annex of ‘Sterile Medicinal Products’, introduced as supportive document of ‘quality management regulation of medical manufacture (revised in 2010)’, has also been carried into effect from the 1st March 2011. It is emphasized in the annex that materials preparation, manufacture and distribution of product, filling and packing must be done separately in the clean area.

The level of clean area for manufacturing sterile medical products should be defined in accordance with elements

as product characteristics, technology, equipment, etc. Environment for every step of the manufacturing process should reach the dynamic cleanness standard, and the risk of particulate or microbial contamination for products or materials under the process should be controlled as much as possible. Five years later, the pharmaceutical industry continues to innovate around meeting these standards.

Increased Demand for Combination Products: Self-administration and biologics have only increased the popularity of combination products, such as wearable auto-injector systems used for the management of chronic diseases.

Biologics, which are primarily being administered through injections, have played a large part in the demand for combination products. Auto-injectors, wearables and other new systems will only increase the already budding demand in the coming years as APAC companies create them for export to Europe and the Americas; in the longerterm there is no doubt that other global

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enquiries@SELECTBIO.com +44 (0)1787 275645 www.pharmafocusasia.com

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regions will embrace them as their own health systems evolve.

Flexible Manufacturing Enables Personalised Medicine: Many pharmaceutical companies are looking for ways to institute adaptive filling techniques. Flexible manufacturing allows systems to be adjusted for a variety of dosage forms which, in turn, potentially reduces costs and space requirements. A primary driver of flexible manufacturing is the healthcare system’s ongoing shift to personalised medicine, leading to smaller quantities of drug products and more sophisticated therapies, such as biologics.

Flexible manufacturing enables drug companies to quickly transition fill lines from vial format to cartridge to pre-filled syringes, depending on the needs of the injectable medicine. Injectable drug delivery system manufacturers will be tasked with creating innovative meth-

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ods to allow adaptive filling to occur.

Although commercial utilisation of flexible manufacturing is likely further down the road, some pharmaceutical companies have started to examine its utility around clinical trials, where smaller quantities are needed.

The Rise of Continuous Manufacturing Methodologies: To date, the pharmaceutical industry has been largely focused on manufacturing in batch quantities. The process is quite straight forward: make a certain number of batches, validate and submit the data. However, this method is somewhat behind the curve when compared to other manufacturing operations, such as oil refining, steel casting, paper production and natural gas processing. Expect pharma to continue to explore continuous manufacturing, where product testing occurs during the production process using real-time analytics to identify and

react to irregular trends. The result is an increase in quality and a higher level of confidence throughout the process.

Continuous manufacturing also offers greater cost reduction because production doesn’t have to stop between each batch and it drastically reduces the amount of unusable end products. Although historically, this has been a bit of a challenge for pharma, the introduction of different techniques and process analytical technologies—part of which is driven by QbD approaches – is pushing the industry in this new, data-driven direction.

Orphan Disease Treatments Drive Smaller Batches: On the other side of the ‘batch vs. continuous manufacturing coin, orphan diseases’-rare conditions that decades ago would not have been sustainable to create traditional drugs -can be treated with new biologics under development. Small pharmaceutical companies with agile research

MANUFACTURING

delivery options that can improve the patient experience while ensuring, when possible, a delivery format that patients are currently familiar and comfortable with.

In the broader sense, there will be continuing growth in emerging markets -especially in India-driven by increasing access to healthcare. The advent of

biosimilars may open opportunities for increased access to biologics. This is a significant area of opportunity for many companies planning to enter the market with biosimilars versions of key drugs like Enbrel®, Humira® and Remicade®, while innovators continue to explore new indications and options for lifecycle management.

Looking beyond 2017 It has often been stated that “drugs don’t work in patients that don’t take them,” and it is clear that pharmaceutical and biotech companies are spending a huge amount of effort on ways to improve patient adherence. Such a venture can be enhanced by newer capabilities in terms of connected health systems, as well as a more thorough understanding of patient psychology. In many cases, rewards are seen as a greater motivator than reminders.

In addition, increasing emphasis is being placed on patient on-boarding and training. Compliance rates for chronic medicines are low, and it has been shown that many patients do not use devices correctly. Connected health systems offer access to huge amounts of data that can help understand patient behaviour. We have already seen increased awareness by patients, which is supported by access to information on specific medicines, social-media-based communication and increased advertising. The advent of connected health devices will further increase patients’ ability to monitor and control their healthcare.

In summary, there is a need for an increased focus on patient outcomes, while ensuring a continued focus on integrated drug delivery systems. Early collaboration between pharmaceutical and biotech companies and a range of key partners will be critical to ensure optimum speed to market, effective drug delivery, and enhanced outcomes for patients around the world.

A u t h o r BIO

teams will bring smaller-batch drugs to market. But they will have special considerations such as short shelf life, creating just-in-time manufacturing challenges to meet.

These companies will rely on packaging partners to help select and design the most appropriate, patient-centric delivery systems so they can concentrate on creating the most effective molecules to treat patients in need. The packaging partners will have to also create agile methods that may revolve around the ability to ship a single crate of product with flexible manufacturing methods – instead of pallets and truckloads at a time.

Supply Chain Risk Mitigation: Typically, when examining supply chain risk, factors such as transportation, political climate and global economics are considered. For obvious reasons, supply chain disruption can have a very adverse impact in delivering needed pharmaceutical products, including packaging/delivery systems, to the end user.

Because of this, we are now seeing increased discussion in the injectable sector around the origin of materials and the ability to quickly shift to another region should one be compromised by natural disasters or other natural irregularities that compromise safety. As risk management technologies continue to improve, pharmaceutical companies have greater insights into the probability that supply chain risks may occur and, in turn, allow the industry to react more quickly to avoid disruption.

Biosimilars Control Costs, Need Delivery Differentiation: 2015 saw the first FDA-approved biosimilar, and this was just the tip of the proverbial iceberg in the US market. Biosimilars cost a fraction to bring to market compared to biologics. With several companies competing for the same biosimilar, the mechanism of administration can be a key differentiator. For injectable biosimilars currently in the pipeline, it will be important to examine drug

Troy Player is responsible for driving revenues and operations across Asia Pacific, and developing long-term operations and strategic business plans to ensure West’s continuous growth in the region. With more than 25 years in the healthcare industry, Mr. Player has a keen understanding of his customers and market’s needs.

He first joined West in 2003 and served in several senior positions in the Americas region, including Vice President of Operations, Senior Director of Operations and Director of Sales, before assuming his current role. During his tenure as the Senior Director of Operations, Mr. Player was responsible for driving business performance of nine facilities in the Americas region and delivered 73 per cent increase in revenue over a five-year period.

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Dates announced for MEDICAL FAIR THAILAND 2017

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The 8th edition of MEDICAL FAIR THAILAND, the leading medical and healthcare event in Thailand and the region, will take place at the Queen Sirikit National Convention Centre (QSNCC) in Bangkok, Thailand from 6 – 8 September 2017.

from 42 countries including 15 national pavilions and country groups from Austria, Belgium, China, France, Germany, Japan, Malaysia, Singapore, South Korea, Taiwan, Thailand, UK and for the first time the USA, Turkey and Italy.

Since its inception in 2003, MEDICAL FAIR THAILAND has grown in size, stature and is recognised as Thailand’s most important resource and business platform for both international and regional suppliers from the medical and healthcare sectors.

The testament to the exhibition’s success was further reflected in the number of visitors, as the 7th edition welcomed 7,226 quality trade buyers and decision makers from mainly Thailand and the ASEAN region.

In 2015, MEDICAL FAIR THAILAND held its largest edition to date as it welcomed 600 exhibitors

Focused on equipment and supplies for the hospital, diagnostic, pharmaceutical, medical and reha-

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government bodies, hospital administrators, doctors, nurses and other healthcare professionals sourcing for the latest innovations in medical and healthcare, MEDICAL FAIR THAILAND 2017 is expected to draw 700 exhibitors, 17 national pavilions and country groups and 8,500 quality trade visitors.

Bookings for exhibitor spaces are now open and exhibitors are urged to secure their booth space early. More information on MEDICAL FAIR THAILAND 2017 can be found at medicalfair-thailand.com

About Messe Düsseldorf Asia

bilitation sectors, MEDICAL FAIR THAILAND 2017 will once again bring together new and innovative technologies, solutions, products and services from around the world.

In its upcoming edition, the exhibition will emphasise on Connected Healthcare and Geriatric Rehabilitative Care across two dedicated platforms and numerous concurrently held events. For one, the Connected Healthcare platform aims to demonstrate innovative digital solutions such as wearables that are transforming the understanding of patient’s health statuses, improve care and deliver greater results. At the same time, and returning for its 3rd edition, the Advanced Rehab Technology Conference (ARTeC) will focus on innovative and effective technological solutions to decrease mobility related disabilities.

Co-organised by the Thai Rehabilitation Medicine Association, the Royal College of Physiatrists of Thailand and Messe Düsseldorf Asia, the academic conference will welcome international key thought leaders to share insights on robotic transfer systems, robotic arm training devices, robotic gait training and wearable devices.

Serving as a converging point for healthcare providers, medical suppliers, industry professionals,

Messe Düsseldorf Asia is a subsidiary of Messe Düsseldorf in Germany, one of the world’s leading trade fair organisers, responsible for organising more than 20 global No.1 exhibitions in various industries including medicine and health, specifically MEDICA, COMPAMED and REHACARE INTERNATIONAL held in Düsseldorf, Germany. With extensive expertise in organising trade fairs in Southeast Asia, Messe Düsseldorf Asia has developed a portfolio of numerous trade fairs in the region since 1995.

For more information, please visit: www.medicalfair-thailand.com For more information on the exhibition please contact: Exhibitor Contact:

Daphne Yeo

Senior Project Manager Tel: (65) 6332 9682 medicalfair-asia@mda.com.sg Press Contact:

Maria Wesson

Senior Marketing & Communications Executive Tel: (65) 6332 9652 maria@mda.com.sg Advertorial www.pharmafocusasia.com

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Our Esteemed Clients Bachem – Your Partner for Selective Chemical Glycosylation Bachem provides comprehensive services to the pharma and biotech industries. It specializes in the development of innovative, efficient manufacturing processes and the reliable production of peptide-based APIs. A new service in Bachem’s portfolio is the selective chemical glycosylation.

Selective, site-specific glycosylation leads to a homogeneous product with potential for more defined bioactivity compared to heterogeneous products.

The glycosylation technology permits the synthesis of peptides and proteins with pre-attached sugars, selected from a proprietary library of over 50 specific glycans. It has been shown to markedly improve drug properties such as half-life, binding affinity and selectivity. Furthermore, compared

the groundbreaking work on Interferon ß-1a. The technology has been used in multiple other projects, such as to manufacture glycosylated somatostatin analogues and glycosylated GLP-1. In all cases, drug improvements were achieved.

Interferon ß-1a is a glycosylated 166 amino acid protein and an approved drug substance to treat multiple sclerosis.

to recombinant products, the chemically synthesized proteins are more homogeneous.

The technology is applicable to large scale and has the potential to be applied to a variety of peptides, where Bachem can pioneer the concept of improving current and future drugs.

Headquartered in Switzerland with subsidiaries in Europe and the US, the group has a global reach with more experience and know-how than any other company in the industry.

Towards its customers, Bachem shows total commitment to quality, innovation and partnership.

Bachem.Pioneering Partner for Peptides.

Bachem AG and GlyTech Inc. were 2013 CPhI innovation prize finalists for

Eppendorf – A Leading Life Science Company Eppendorf is a leading life science company that develops and sells instruments, consumables, and services for liquid handling, sample handling, and cell handling in laboratories worldwide. Its product range includes pipettes and automated pipetting systems, dispensers, centrifuges, mixers, spectrometers, and DNA amplification equipment as well as ultra-low temperature freezers, fermentors, bioreactors, CO2 incubators, shakers, and cell manipulation systems. Consumables such as pipette tips, test tubes, microliter plates, and single-use bioreactor vessels complement the range of highest-quality premium products.

Eppendorf products are most broadly used in academic and commercial

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research laboratories, e.g., in companies from the pharmaceutical and biotechnological as well as the chemical and food industries. They are also aimed at clinical and environmental analysis laboratories, forensics, and at industrial laboratories performing process analysis, production, and quality assurance.

Eppendorf was founded in Hamburg, Germany in 1945 and has about 3,000 employees worldwide. The company has subsidiaries in 25 countries and is represented in all other markets by distributors.

FPS – Innovative Solutions for Containment, Milling and Micronization FPS is specialized in fine size reduction equipment and containment systems for many industrial applications. Containment is a general approach, allowing us to propose solutions starting from clean rooms up to isolators for sterile or HPAPI manufacturing needs.

Containment is an issue more and more addressed by authorities and companies in fine chemical and pharmaceutical industries with increasing demand also in energy, aerospace, food and cosmetic applications.

Product protection, as well as environment and operator protection, is the driving requirements in new projects or in equipment re-vamping.

We offer a complete range of containment systems that satisfies all possible needs and requirements. Our

available to define the most suitable configuration for your fine grinding needs.

FPS product range is made of three technologies: Spiral JetMill, QMill and PinMill.

approach to a containment system is to discuss with the end user the specific needs in terms of protection, quality, and productivity in order to identify the equipment that best fits the specifications.

Spiral jet mill technology is suggested for target particle size distributions of less than 3μm, while QMill or PinMill technology is suitable for PSD in the range 30-100μm.

Contact us at info@foodpharmasystems.com or visit our web site.

FPS micronisation technology considers both fluid jet mills and mechanical mills to assure the widest fine grinding capabilities. FPS process experts are

MECO – Our Product is Pure Water, Our Business is Solutions

MECO is a world leader in the design and construction of engineered solutions for water purification serving multiple industries where water is the critical utility. Our need-specific systems meet the strict criteria of each and every client. We build our water plants to last using only the best parts and components available.

ABOUT MECO BIOPARMACEUTICAL

With over 1,000 water purification machines successfully installed across

MECO Corporate Office

the globe, MECO serves leading pharmaceutical and biotech companies with over 25 million gallons of product water each day. The MECO global portfolio includes the broadest range of engineered products for pure steam, purified water and Water for Injection (WFI). Our patented vapor compression technology with the GII Centurbo™ Compressor sets the industry standard for quality, reliability and efficiency. Our engineered solutions are backed by reliable and

responsive service personnel through our MASTERsupport™ service center.

This depth of global experience and service support ensures we understand the critical nature of maximized uptime for plant operations.

MECO OFFICE LOCATIONS

Asia-Pacific: Singapore I +65.6836.7500 Europe: Ireland I +353.61.512.130 United Arab Emirates Abu Dhabi I +971.2.774.400 United States: Houston, Tx I 281.276.7600 Mandeville, La I 985.249.5500 www.MECO.com

MECO Product lineup

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Our Esteemed Clients Shanghai World of Packaging (swop) – The Interpack Trade Fair innovation and development opportunities. swop is an excellent display and communication platform for the entire packaging industry. Regardless of whether you are a manufacturer of processing and packaging machinery equipment or a supplier of packaging materials and products, swop 2017 will not only provide you with an immediate "supply and demand" platform for the packaging market, but will also give you insights into future packaging trends.

Since 1958, the interpack trade fair in Düsseldorf has presented tangible evidence of the processing and packaging industry’s global success. interpack alliance is based on interpack, the world's leading processing and packaging trade fair, spanning all international events staged by Messe Düsseldorf under its processing & packaging portfolio. As a member of interpack alliance, Shanghai World of Packaging (swop) will be held at the Shanghai New International Expo Center on November 7-10, 2017 and will benefit from the global network, expertise and resources of interpack. swop addresses the target groups of food, beverages, confectionery, baked goods, pharmaceutics, cosmetics, non-food consumer goods and industrial products in key emerging markets. Domestic and regional

manufacturers of processing and packaging machinery will receive a boost in their search for business,

Turkish Cargo – Time and Temperature Sensitive Products Handled with Care and Expertise Turkish Cargo has been carrying out its operations of transporting and storing time and temperature sensitive healthcare and pharmaceutical products successfully with many years of experience. We carry out our cargo operations in line with special schedules established for cold chain logistics and ensure the punctual transportation of these supplies to over 100 countries around the world.

Turkish Cargo’s Temperature controlled logistics are prepared specifically in order to protect the contents and prevent them from deterioration. At the acceptance stage, all transportation of healthcare and pharmaceutical products are executed in accordance with the IATA Acceptance Checklist, to be accepted through special delivery doors dedicated to pharmaceutical

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rate special cargo rooms, including active temperature controlled storage units for medical supply shipments.

All Turkish Cargo staff participate in international and in-house training and certification programs.

shipments and located in a place close to x-ray scanners.

Our new cargo terminal has 3.000 m2 special storage area and 41 sepa-

To prevent cargoes from being exposed to often-changing temperature conditions during flights, we use Envirotainer active temperature controlled containers. We maintain constant and desired temperature throughout the entire cold chain even to long-distance destinations. We can realize shipments between -20°C and +25°C at demanded circumstances and capacities.

Vetter - Your Partner in Aseptic Filling and Packaging Vetter is a leading contract development and manufacturing organization (CDMO) that specializes in the aseptic filling of syringes, cartridges and vials. The company has extensive experience with biologics and other complex compounds, including monoclonal antibodies, peptides, interferons and vaccines. More than 80% of Vetter’s active projects are biologics. Collaborating with the top 10 (bio-)pharmaceutical companies worldwide, Vetter supports products from preclinical development through global market supply. Through its U.S. and European facilities, Vetter Development Service provides stateof-the-art support for early-stage products, with seamless transfer at Phase III to Vetter Commercial Manufacturing for large-scale production. The company offers state-of-theart technology and innovative proc-

esses to promote product quality and maximize API yield.

Vetter at a glance:

• Global experience and expertise with regulatory authorities including FDA, EMA, PMDA (Japan), and RP (Germany)

• Headquarters in Ravensburg, Germany

• Approx. 50 customer products with FDA approval

• Additional clinical development facility in Chicago, US

For more information please contact us at infoAsiaPacific@vetterpharma.com and visit our website: www.vetter-pharma.com

• A Representative office for Asia Pacific in Singapore and a subsidiary in Japan • Approximately 4,100 employees • Worldwide specialist in the aseptic production of prefilled drug delivery systems

World Courier – The Most Trusted Specialty Logistics Company in the World World Courier is a global specialty logistics company that for 40+ years designs world-class logistics and supply chain programs in complete alignment with our customers’ business goals. Companies trust us to transport and store their time- and temperature-sensitive products because they value the peace of mind that comes with our unsurpassed knowledge, global reach and flawless supply chain execution. World Courier is part of the global Fortune #12 drug distribution company AmerisourceBergen (NYSE: ABC).

Each trusted partnership we form with a customer is deeply rooted in our shared vision of improving global health. With 14 strategically located storage depots, more than 2,000 associates and 140+ offices

in more than 50 countries, we offer solutions that instill confidence in the on-time, on-temperature delivery of critical products. No other specialty logistics company has the experienced personnel, global offices and in-market expertise required to ensure the optimal handling, transport and delivery of vital healthcare products. When trust is absolutely essential, there’s only one choice: World Courier.

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Our Esteemed Clients Lufthansa Cargo – Networking the World Lufthansa Cargo ranks among the world’s leading cargo carriers.

In the 2014 business year, the airline transported around 1.7 million tonnes of freight and mail and sold 8.6 billion revenue ton-kilometers. The company currently employs more than 4,500 people, worldwide.

Lufthansa Cargo focuses on the airport-to-airport business. The cargo carrier serves around 300 destinations in more than 100 countries with its own fleet of freighters, the belly capacities of passenger aircraft operated by Lufthansa and Austrian Airlines, and an extensive road feeder service network. The bulk of the cargo business is routed through Frankfurt Airport. Lufthansa Cargo is a wholly owned subsidiary of Deutsche Lufthansa AG.

MEDICAL FAIR THAILAND – Medical and Healthcare Trade Event With a well-established history since 2003, MEDICAL FAIR THAILAND continues to grow from strength to strength as the region’s No. 1 medical and health care event. Focused on equipment and supplies for the hospital, diagnostic, pharmaceutical, medical and rehabilitation sectors, MEDICAL FAIR THAILAND provides you with the best business opportunities to navigate the dynamic marketplace of Thailand and Southeast Asia.

Supported by some of Thailand’s and the region’s most prominent government and industry trade associations, including Thailand’s Ministry of Health, the Asian Hospital Federation, and many others, MEDICAL FAIR THAILAND is the ideal platform for your business.

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Organised by Messe Düsseldorf Asia, MEDICAL FAIR THAILAND is modelled after MEDICAL FAIR ASIA and is part of the globally recognised and leading medical and health care trade event under the Messe Düsseldorf group – MEDICA.

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Research Insights A randomised controlled trial of a comprehensive breast cancer treatment patient decision tool (iCanDecide) Authors:

Sarah T Hawley, Yun Li, L Alexandra Jeanpierre, Stefanie Goodell, Reshma Jagsi, Kevin C Ward, Michael S Sabel, Steven J Katz Abstract Background Patients newly diagnosed with breast cancer face a series of complex decisions regarding locoregional and systemic treatment. There is a need to improve the quality of locoregional and systemic decisions for breast cancer patients, and to help patients understand the role of evaluative tests in this decision process.

We are now conducting a randomised controlled trial (RCT) of an online decision tool—called iCanDecide, which we expect will help patients with these difficult decisions. Furthermore, the results of this RCT will be highly relevant to future breast cancer patients making these decisions and to their clinicians.

Methods This is a two-arm randomised controlled trial with the target of 222 participants per arm. Participants are recruited from 25 surgical practices (total 40 surgeons) and 2 medical oncology practices (total 2 oncologists) in Michigan, Georgia, Tennessee, and California. Participants are newly-diagnosed female breast cancer patients between 21 and 84 years, with stage I-II invasive breast cancer or ductal carcinoma in situ (DCIS) and who are eligible for and considering either mastectomy or lumpectomy with radiation, and who may be eligible for adjuvant systemic treatment.

The RCT tests an interactive, tailored website, called iCanDecide (intervention arm), compared to a static version of the website (control arm). The static control arm is designed to include the same basic content as the intervention version, but without tailoring and interactive features. The primary outcome includes the rate of making a high-quality decision. The hypothesis is that patients randomised to the interactive version of iCanDecide will have higher rates of high quality decisions (informed and values-concordant), and will appraise their decision-making process more positively, for both surgical and systemic treatment.

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Discussion The goal of this study is to evaluate the impact of the iCanDecide interactive website on decisionmaking for locoregional and systemic breast cancer treatments. The results of this study will be important for future breast cancer patients and their clinicians as we determine how to better individualize decision making across this complex treatment landscape.

Trial registration ClinicalTrials.gov ID NCT01840163.

Keywords • Breast cancer; • Decision tool; • Decision-making; • Health communication Abbreviations used • DCIS, Ductal Carcinoma In Situ; • GEE, Generalized Estimating Equation; • RCT, Randomised Controlled Trial; • SEER, Surveillance, Epidemiology, and End Results Program 1. Introduction Patients newly diagnosed with breast cancer face a series of complex decisions regarding locoregional and systemic treatment. Currently many of these decisions do not meet the definition of a high-quality decision, defined as one that is both informed (i.e., based on an accurate understanding of the treatment risks and benefits) and values- concordant (i.e., consistent with the patients' underlying values for attributes of treatment) [1]. Moreover, the introduction of

evaluative tests has made these decisions more complicated for many patients [2] and [3]. Decision aids and tools have been developed to help breast cancer patients with treatment decision making.

While some have had positive impacts on knowledge about treatment options, most have not had a long standing effect on decision outcomes (e.g., decision satisfaction or regret) [4] and none have been specifically evaluated for impact on decision quality as defined above.

Furthermore, existing decision aids have not used tailoring to identify treatment-related knowledge deficits and provide patients with accurate information based on these deficits. In addition, no current tools provide tailored feedback to users based on stage of treatment planning, decision preparedness and/or their perceptions of their experience communicating about treatment with clinicians.

A few have included a values clarification exercise, intended to elicit their values for treatment attributes (e.g., if they prefer to retain their natural breast or avoid radiation therapy) [5] and [6], but do not provide patients with direct feedback regarding which treatment attributes were most important to them and how these match existing treatments. Existing decision aids also do not have a focus on improving decision quality in both locoregional and systemic treatments. Finally, most of them were evaluated in academic settings, rather than community practices.

Thus, there is a need to improve the quality of locoregional and systemic treatment decisions for breast cancer patients, and to help patients understand the role of evaluative tests in the decision process.

Ensuring patients can deliberate effectively about these decisions, assert their views and communicate with their clinicians is likely to improve their overall decision preparedness and satisfaction.

This study will focus on improving individualized care by evaluating the impact of an innovative decision tool on locoregional and systemic therapy decision making for newly diagnosed breast cancer patients diagnosed in community surgical practices. The online decision tool was developed and tested two years prior to launching the study [7]. Pilot data suggested that this tool has a positive impact on patient knowledge and decision outcomes. However, the prototype did not include key components necessary for improving decision quality, such as knowledge assessment and tailoring and patient activation. Further, the prototype was evaluated in academic settings and not

in community practices where most breast cancer patients receive care.

We are now conducting a randomised controlled trial (RCT) of an updated and enhanced version of this online decision toolâ&#x20AC;&#x201D;called iCanDecide-- in newly diagnosed patients (expected N = 444) with invasive early stage breast cancer or DCIS in community practices, compared with the static version initially developed in our pilot study. Patients that view the iCanDecide website are being randomised to either the enhanced interactive, tailored version (intervention) or a non-tailored, static version (control). Thus, all participants in the trial receive information to help them with their treatment decision; but delivered in different ways. As noted above, the primary outcome is a high-quality decision (defined as an informed and values concordant treatment choice) [1] for both locoregional and systemic breast cancer treatments. The hypothesis is that patients randomised to the interactive version of iCanDecide will have higher rates of high-quality decisions. The secondary hypothesis is that patients in the intervention arm will appraise their decisionmaking process (decision preparedness, deliberation, and satisfaction) more positively, for both locoregional and systemic treatment (see Fig. 1).

The results of this RCT will be highly relevant to future breast cancer patients making these decisions and to their clinicians. The aims are: Aim 1: To evaluate the impact of an online comprehensive decision tool (iCanDecide) on decision making for locoregional treatment among newly diagnosed patients with early stage breast cancer, compared to standard online information.

H1a.

Patients in the intervention arm will have a higher rate of high-quality decisions about locoregional treatment (i.e., accurate knowledge about treatment options and their risks and benefits and a higher rate of values-concordant treatment decisions).

H1b.

Patients in the intervention arm will report more positive appraisal of the locoregional treatment decision-making process (decision preparedness, deliberation and satisfaction).

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Research Insights Fig. 1: Shows the conceptual framework for the hypothesized association between the interactive version of iCanDecide and the primary outcomes of the study. This model is informed by several existing theories, including the Health Belief Model, Social Learning Theory, the Behavioral Model of Health Services Utilization [8], [9], [10] and [11] and by our preliminary studies [8], [12], [13], [14] and [15].

Aim 2: To evaluate the impact of the iCanDecide tool on decision making for adjuvant systemic therapy among newly diagnosed patients with early stage invasive breast cancer, compared to standard online information.

H2a.

Patients in the intervention arm will have a higher rate of high-quality decisions related to adjuvant systemic therapy (i.e., accurate knowledge of treatment options and their risks and benefits and a higher rate of values-concordant treatment decisions).

H2b.

Patients in the intervention arm will report more positive appraisal of the systemic therapy decisionmaking process (decision preparedness, deliberation and satisfaction).

Competing interests The authors declare that they have no competing interests.

Funding This research was supported by the National Cancer Institute of the National Institutes of Health (P01CA163233) and the University of Michigan Comprehensive Cancer Center Support Grant (5 P30 CA46592).

Acknowledgements We would like to acknowledge the significant contributions of our participating practices from Michigan (Drs. Shannon Bongers, Nayana Dekhne, and Nicole Walker from Beaumont Health System; Drs. Eric Brown and Linsey Gold at Comprehensive 56

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Breast Care; Drs. Jeffrey Falk and Cheryl Wesen from Michigan Breast Specialists at St. John Providence; Dr. Narendra Gohel affiliated with St. John Providence; Dr. David Siegel affiliated with St. John Macomb – Oakland; Dr. Keith Hinshaw from Rochester General Surgery; Dr. Pamela Johnson; Dr. Amy Kirby affiliated with St. Joseph Mercy Oakland; Dr. Raouf Mikhail affiliated with Hurley Medical Center; and Drs. Jessica Bensenhaver, Jacqueline Jeruss, Lisa Newman, and Michael Sabel from the University of Michigan Cancer Center); from Georgia (Dr. Jennifer Amerson from Breast Care Specialists; Drs. William Barber, Amanda Morehouse, and Erin Bowman from Atlanta Breast Care; Drs. Sheryl Gabram, Joel Okoli, and Derrick Beech at Grady Memorial Hospital/Emory; Dr. Cheryl Jones at Georgia Cancer Specialists affiliated with Northside Hospital; Dr. John Kennedy from Dekalb Surgical Associates; Drs. Keith Martin and Thomas Woodyard affiliated with Coliseum Health System; Dr. Monica Rizzo from Emory Healthcare; Drs. David Ruben, Patrick Luke, and Iqbal Garcha affiliated with Northside Hospital); from Tennessee (Drs. Alyssa Throckmorton and Lindi VanderWalde at Baptist Medical Group - Memphis Breast Care) and from the Los Angeles area (Drs. Deanna Attai and Maurice Berkowitz affiliated with the University of California, Los Angeles Health System).

Copyright © 2017 Elsevier B.V. or its licensors or contributors. ScienceDirect ® is a registered trademark of Elsevier B.V. Received 22 November 2016, Revised 30 January 2017, Accepted 1 February 2017, Available online 3 February 2017

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Books

Biosimilars of Monoclonal Antibodies: A Practical Guide to Manufacturing, Preclinical, and Clinical Development

Drug Safety Evaluation (Pharmaceutical Development Series)

Author: Elizabeth Kwong

Author: Shayne Cox Gad

Author: Cheng Liu, K John Morrow Jr.

Year of Publishing: 2017

Year of Publishing: 2016

Year of Publishing: 2017

No. of Pages: 272

No. of Pages: 920

No. of Pages: 704

Description: Detailing formulation approaches by stage of discovery to early development, this book gives a “playbook” of practical and efficient strategies to formulate drug candidates with the least chance of failing in clinical development.

Description: The definitive safety guide to all aspects of the drug development process

Description: Biosimilars of Monoclonal Antibodies: A Practical Guide to Manufacturing and Preclinical and Clinical Development gives pharmaceutical and biotech scientists and researchers a clear resource to understand the scientific principles and challenges involved in biosimilar drug development.

The book discusses the scientific background including history, classification, and biological activities including background knowledge unique to monoclonal antibody (mAb) drugs and essential profiling characteristics that regulations require. Contributing authors from the frontlines of biosimilar development address the processes and issues involved with manufacturing biosimilar mAbs, like cell line development, process development, large–scale cell culture of mammalian cells, and final product analysis.

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Oral Formulation Roadmap from Early Drug Discovery to Development

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• Comes from contributing authors with experience developing formulations on the frontlines of the pharmaceutical industry • Focuses on pre (or non-) clinical and early stage development, the phases where most compounds are used in drug research • Features case studies to illustrate practical challenges and solutions in formulation selection • Covers regulatory filing, drug metabolism and physical and chemical properties, toxicology formulation, Biopharmaceutics Classification System (BCS), screening approaches, early stage clinical formulation development, and outsourcing.

The third edition of Drug Safety Evaluation continues and expands on the comprehensive resource its predecessors offered an all–inclusive, practical guide for those who are responsible for ensuring the safety of drugs and biologics for patients, for health care providers, for those involved in the manufacture of medicinal products, and for all those who need to understand how the safety of these products is evaluated.

In the new edition, changes and updates reflect the many changes in the scope of products (small synthetic, large protein moieties and cells and tissues), harmonized global and national regulatory requirements, the therapeutic development process, and available technologies to identify and evaluate the relevance of potential patient risks. They address specific approaches to evaluating hazards, including problems that are encountered and their solutions.

Managing the Drug Discovery Process: How to Make It More Efficient and Cost-Effective

3D Bioprinting: Fundamentals, Principles and Applications

Year of Publishing: 2016

Year of Publishing: 2016

Author: Walter Moos, Susan Miller, Stephen Munk, Barbara Munk

No. of Pages: 292

Year of Publishing: 2016

Description: Retaining the successful approach found in the previous volume in this series, the inventors and primary developers of drugs that successfully made it to market tell the story of the drugs discovery and development and relate the often twisted route from the first candidate molecule to the final marketed drug.

No. of Pages: 536

Successful Drug Discovery, Volume 2 Author: Janos E Childers

Fischer,

Wayne

Eleven selected case studies describe recently introduced drugs that have not been previously covered in textbooks or general references. These range across six different therapeutic fields and provide a representative crossâ&#x20AC;&#x201C;section of the current drug development efforts. Backed by copious data and chemical information, the insight and experience of the contributors makes this one of the most useful training manuals that a junior medicinal chemist can hope to find and has won the support and endorsement of IUPAC.

Description: Managing the Drug Discovery Process: How to Make It More Efficient and Cost-Effective thoroughly examines the current state of pharmaceutical research and development by providing chemistry-based perspectives on biomedical research, drug hunting and innovation. The book also considers the interplay of stakeholders, consumers, and the drug firm with attendant factors, including those that are technical, legal, economic, demographic, political, social, ecological, and infrastructural. Since drug research can be a high-risk, high-payoff industry, it is important to researchers to effectively and strategically manage the drug discovery process.

This book takes a closer look at increasing pre-approval costs for new drugs and examines not only why these increases occur, but also how they can be overcome to ensure a robust pharmacoeconomic future.

Author: Ibrahim Tarik Ozbolat No. of Pages: 344 Description: 3D Bioprinting: Fundamentals, Principles and Applications provides the latest information on the fundamentals, principles, physics, and applications of 3D bioprinting. It contains descriptions of the various bioprinting processes and technologies used in additive biomanufacturing of tissue constructs, tissues, and organs using living cells. The increasing availability and decreasing costs of 3D printing technologies are driving its use to meet medical needs, and this book provides an overview of these technologies and their integration. Each chapter discusses current limitations on the relevant technology, giving future perspectives.

Professor Ozbolat has pulled together expertise from the fields of bioprinting, tissue engineering, tissue fabrication, and 3D printing in his inclusive table of contents. Topics covered include raw materials, processes, machine technology, products, applications, and limitations.

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Products & Services Company.........................................................Page No.

Company.........................................................Page No.

STRATEGY Arena International........................................................ 39 CPhI Korea.................................................................... 23 Eppendorf AG............................................................... 48 EPM Group................................................................... 37 FCE Pharma.................................................................. 19 Financial Times Live...................................................... 13 Global Engage Ltd ....................................................... 27 IMAPAC......................................................................... 33 IMUS.............................................................................. 09 Messe Duesseldorf Asia.............................. 15, 46-47, 52 Messe Düsseldorf (Shanghai) Co., Ltd.................. 03, 50 SELECTBIO Ltd............................................................. 43

F.P.S. Food and Pharma Systems Srl........................... 49 Vetter Pharma....................................................... IBC, 51

RESEARCH & DEVELOPMENT Bachem AG................................................................... 48 BOSCH India................................................................. 05 Eppendorf AG............................................................... 48 MECO............................................................................ 49

CLINICAL TRAILS Vetter Pharma............................................................. IBC MANUFACTURING Bachem AG................................................................... 48 BOSCH India................................................................. 05 Eppendorf AG............................................................... 48 F.P.S. Food and Pharma Systems Srl........................... 49 Lufthansa Cargo AG..................................................... 52 MECO............................................................................ 49 Turkish Cargo...................................................... OBC, 50 Vetter Pharma....................................................... IBC, 51 World Courier........................................................ IFC, 51 INFORMATION TECHNOLOGY Eppendorf AG............................................................... 48 FCE Pharma.................................................................. 19

Suppliers Guide Company.........................................................Page No.

Company.........................................................Page No.

Arena International....................................................... 39 www.arena-international.com/ctssoutheast

IMAPAC........................................................................ 33 www.imapac.com/business_conference/biologicsworld-taiwan-2017/

Bachem AG.................................................................. 48 www.bachem.com BOSCH India................................................................ 05 www.boschindia.com CPhI Korea................................................................... 23 www.cphikorea.com Eppendorf AG.............................................................. 48 www.eppendorf.com EPM Group.................................................................. 37 https://biotechpharmasummit.com/ FCE Pharma................................................................. 19 www.fcepharma.com.br Financial Times Live..................................................... 13 live.ft.om/AsiaHCLS F.P.S. Food and Pharma Systems Srl.......................... 49 www.foodpharmasystems.com Global Engage Ltd....................................................... 27 www.global-engage.com/event/probiotics-asia/

IUMS............................................................................. 09 www.iums2017singapore.com Lufthansa Cargo AG.................................................... 52 www.lufthansa-cargo.com MECO........................................................................... 49 www.meco.com Messe Duesseldorf Asia............................. 15, 46-47, 52 www.medicalfair-thailand.com Messe Düsseldorf (Shanghai) Co., Ltd................. 03, 50 http://swop-online.com/en/ SELECTBIO Ltd............................................................ 43 SELECTBIO.com/ADD2017 Turkish Cargo......................................................OBC, 50 www.turkishcargo.com Vetter Pharma...................................................... IBC, 51 www.vetter-pharma.com World Courier........................................................IFC, 51 www.worldcourier.com

To receive more information on products & services advertised in this issue, please fill up the "Info Request Form" provided with the magazine and fax it, or fill it online at www.pharmafocusasia.com by clicking "Request Client Info" link.

1.IFC: Inside Front Cover 2.IBC: Inside Back Cove 3.OBC: Outside Back Cover

“The interview titled "Biotechnology A solution or a problem" published in Pharma Focus Asia, Issue 22, July 2015, was erroneously mentioned as 'Advertorial'. Misprint regretted. Appreciate your patience”.

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Answers that work www.vetter-pharma.com

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