EPM Jan/Feb 2016

MODERN LOVE SCHOTT EXPLAINS HOW COMBINED ACTIVE INGREDIENTS IN MODERN DRUGS CAN BE STORED SEPARATELY AND ADMINISTERED EASILY PLUS INDUSTRY EXPERTS REVEAL THEIR PREDICTIONS FOR 2016 HOW SUSTAINABLE IS PHARMACEUTICAL MANUFACTURE? ADVICE ON STAYING SAFE IN PHARMA

JANUARY/FEBRUARY 2016

M

Y

Y

Y

Contents

January/February 2016 | Volume 16 Issue 1

6 Features

Regulars 5

20

COMMENT

WHAT LIES AHEAD Key sector players look into their crystal ball for 2016

6 NEWS ANALYSIS

27

12 REGULATORY AFFAIRS

FIVE FACTS ABOUT PERSONALISED MEDICINE

14

28

OPINION Michael Acott, Baird’s CMC, explains how supply chain improvements help move medicines

17

MAKING A SUCCESS

20

CHEMICAL REACTION Featuring Nosopharm

45

associate editor dave gray david.g@rapidnews.com editorial assistant emily hughes, emily.hughes@rapidnews.com publishers mark blezard, duncan wood

31

advertising

35

50

editorial group editor lu rahman, lu.rahman@rapidnews.com

production

Lu Rahman asks who’s flying the flag for sustainability in the pharmaceutical sector

Schott explains how modern drugs can be stored easily in its double chamber cartridge

Tel. +44 (0)1244 680222 Fax. +44 (0)1244 671074 Web: www.epmmagazine.com

Hovione’s Roger Viney offers an insight into the success of the company

GREEN FLAG

COVER STORY

head office Carlton House, Sandpiper Way, Chester Business Park, Chester, CH4 9QE.

GAINING PERSPECTIVE Amit, Karpe, 3M and how the company is viewing the clarification process differently

37 A LA MODE Trends at this year’s Pharmapack

42 SOFT SELL The growing importance of pharmaceutical gelatin

48 SAFE AS HOUSES BS&B Safety Systems explains how to protect against dust explosions

art robert wood

robert anderton tel: +44 (0) 1244 680222, rob@rapidnews.com

subscriptions subscriptions@rapidnews.com qualifying readers Europe - Free, ROW - £115 outside qualifying criteria UK - £80, ROW - £115 please subscribe online at www.epmmagazine.com

Address changes should be emailed to subscriptions@rapidnews.com.

European Pharmaceutical Manufacturer is published by Rapid Life Sciences Ltd. European Pharmaceutical Manufacturer is distributed in electronic and print formats to a combined readership of 14,000 pharmaceutical manufacturing professionals.

Volume 16 Issue 1 © January/February 2016 While every attempt has been made to ensure that the information contained within European Pharmaceutical Manufacturer is accurate, the publisher accepts no liability for information published in error, or for views expressed.

All rights for European Pharmaceutical Manufacturer are reserved and reproduction in part or whole without written permission is strictly prohibited.

BPA Worldwide Membership ISSN No - 2052-4811

XDF - Make Better Tablets I Holland’s patented new elliptical head flat can give 50% more dwell time on your existing press.

Visit www.tablettingscience.com or telephone +44 (0) 115 972 6153

IH_XDF_EPM240x340.indd 1

20/11/2015 14:54

from the editor

Gains without frontiers Based in the North West of England it’s very hard for the EPM team not to be excited about industry news that this region of the UK is becoming a hotspot for UK life sciences. Last year there were reports that over 1,000 life science companies had made the region their home, employing over 38,000 people and bringing in in excess of £10bn in turnover a year.

The UK is a key player on the global life science field.

Within that the North West is taking a lead through its ability to provide medical and pharmaceutical breakthroughs. Offering the key ingredients needed to make this happen – expertise, academic input and infrastructure – the region was recently singled out

by PwC claiming that the “rejuvenation in the North of England demonstrates how the coming together of the right pieces of the puzzle is having a positive impact on UK life sciences”.

Of course, this isn’t the first area in the UK that has been hailed as offering life science expertise. For years, the London-Oxford-Cambridge-triangle has been discusses as a hotbed for life science talent and innovation. More recently West Sussex has hit the headlines with plans to create a life science and health hub.

The UK isn’t alone in having these regions. Similar areas in Germany, Switzerland, Denmark and Sweden have been held up as offering focussed life science expertise. Individual regions attract like-minded companies with the aim of developing pharmaceutical and medical products. Opportunities for collaboration allow further innovation and scientific creativity. As our industry becomes increasingly global, opportunities for knowledgesharing and collaboration become clear.

Best practice, research & development and scientific breakthroughs are to be encouraged and observing the experience of the UK, regions with a dedicated focus not only bring expertise to the fore but they boost

the area’s economy and attract young professionals into long-lasting and rewarding careers. This is highly exciting. The country we live in is largely immaterial.

As an integral part of our industry we should be encouraging the dialogue between companies working in these regions and shouting about the developments being carried out. The growth of science hubs is fantastic new and we should be relishing the future innovation they will foster.

Whatever our geographical location, as an industry we should be looking at ways to commercialise academic research, putting clinical research at the heart of innovation in our respective healthcare systems, encouraging adoption in the wider healthcare sector and promoting our regions as solid investment centres to deliver life science expertise.

In the ‘Strategy for UK Life Science One Year On’ report, David Cameron commented: “We recognise that in order to win the global race, we need to do more to make the most of the UK’s strengths in the life sciences sector: our universities, clinical research base, industry and the NHS. By more closely integrating the UK’s unique advantages, we can attract new investment to our shores, and create new jobs and economic opportunities in an increasingly competitive industry”.

These principles don’t have to be UK-centric. These goals can be applied across Europe to create profitable, innovative hotspots. We should use 2016 as the year to highlight the ground-breaking work life science companies are carrying out and the talent pushing back the boundaries of possibility.

Lu Rahman

WWW.EPMMAGAZINE.COM

14:54

5

NEWS ANALYSIS

Martin Shkreli’s arrest the implications

N

obody escaped the sensational coverage of the arrest of pharma CEO Martin Shkreli, nicknamed ‘the most hated man in America’. While the authorities investigate his actions, what were the ramifications on the wider industry?

Martin Shkreli is best known as the man behind the company responsible for driving up prices on an HIV/AIDS drug by over 5000%.

Shkreli’s former company, Turing Pharmaceuticals, gained notoriety with its price-hiking tactics, which saw it acquiring essential drugs and placing them out of the bracket of affordability for many patients.

When he established Turing Pharmaceuticals (not long after being asked to leave his previous company, Retrophin) he was vague as to the details of his plans: “Our goal is to build a diverse portfolio and pipeline of therapies that can make a significant difference to patients. We are creating a strong, experienced team at Turing with a solid track record of success to execute on our objectives.”

All that changed when Turing acquired the rights to Daraprim, a drug used to treat malaria and toxoplasmosis parasitic infections in pregnant women and patients with HIV. Shkreli became the centre of a media whirlwind when his company hiked the price up to approximately $750 per tablet.

After several months of public backlash, Shkreli was arrested in New York late last year – but on suspicion of offenses entirely unrelated to the price hiking activity.

Instead, it was related to his time as manager of hedge fund MSMB Capital Management and, later, CEO of Retrophin.

Nate Raymond, writing for Reuters in New York said that the arrest was part of a securities fraud probe into the two businesses. Raymond added that "Shkreli, 32, was expected to be charged for illegally using Retrophin assets to pay off debts after MSMB lost millions of dollars".

The news quickly became the leading global trend on Twitter. Author and journalist Jon Ronson tweeted: "Now I'll never get to interview Martin Shkreli, which kind of makes us all victims."

6

Meanwhile Greg Hogben, a British author and supporter of LGBT and women’s rights tweeted: “Martin Shkreli - man who hiked up price of AIDS drug - arrested. Because Karma is beautiful.”

In the days and weeks that followed, the repercussions of yet more bad press and an arrested became clear.

Firstly, Shkreli’s own Twitter account was targetted by hackers, who posted fake messages, such as “Anyone want free money? Willing to donate hundreds of thousands to charities before I go to prison...”

But there were far more serious events taking place as a result of the press attention. Clinical trials involving drugs from Shkreli’s recently acquired KaloBios pharma company were immediately halted.

The Moffitt Cancer Center said in a statement to CNBC that it was “was among several participating sites of the clinical trial 'Study of KB003 in Previously Treated Patients With Chronic Myelomonocytic Leukemia (CMML)'funded by KaloBios.”

The statement continued: “The biopharmaceutical company holds ownership of the clinical trial and KB003 drug. Moffitt has suspended this clinical trial indefinitely pending the outcome of the investigation of KaloBios' CEO, Martin Shkreli,” Turing meanwhile was left scrambling to protect its already-damaged reputation. Following the arrest, Shkreli stood down as CEO, and the firm issued an update on its stance on Daraprim. Chairman of the board at Turing, Ron Tilles, said: "We wish to thank Martin for helping us build Turing Pharmaceuticals into the dynamic research focused company it is today, and wish him the best in his future endeavors. At the same time, I am very excited about the opportunity to guide Turing Pharmaceuticals forward. We remain committed to ensuring that all patients have ready and affordable access to Daraprim and Vecamyl.”

Now, Shkreli’s actions will be scrutinised by congress, but considerable damage has already been done. Turing, for its part, had already unveiled a pricing program for hospitals, giving them access to the drug with discounts of up to 50%.

WWW.EPMMAGAZINE.COM

NEWS ANALYSIS

New groups aims to reduce risk of medication errors cientists are embarking on a new approach to overhaul the system for safe research and use of medicines which will help tackle medication errors.

S

preparation, dispensing, administration and tracing throughout the supply chain. However, it is not known whether this happens consistently and safely.

The Chartered Institute of Ergonomics and Human Factors has set up a group which includes scientists, members of the the pharmaceutical sector and healthcare professionals to examine how society can improve the system for safe and effective medicine.

“We have evidence to demonstrate how humans can perform more effectively in complex systems, but this is not being applied systematically for medicines with so many people and professions being involved who work in their own silos,” he said.

In a review of incidents reported to the National Reporting and Learning System (NRLS) over six years between 2005 to 2010 there were 86,821 of medication incidents reporting actual patient harm, with 822 (0.9%) resulting in death or severe harm. *

The newly-formed Pharmaceutical Human Factors and Ergonomics Group will examine all aspects that influence human behaviour throughout the pharmaceutical system that ultimately impact prescribing and administering medications, for example, leadership and decisionmaking, the work situation, communications and personality.

“We know that errors and adverse reactions from medicines can cause distressing symptoms, loss of function and loss of income. This can cause profound distress to patients and their carers, and contribute to the financial burden for the NHS,” said Dr Brian Edwards from NDA Regulatory Science.

The NHS has established a Never Events list of serious incidents that should be wholly preventable such as (preventable) low blood sugar following an unintentional overdose of insulin. Traditionally investigations of how to reduce harm from unsafe use of medicines have focussed on healthcare professionals within the NHS and not how the broader pharmaceutical system has been working.

Although strategies exist for evaluating a process and assessing the relative impact of different failures, they do not cover all groups collectively associated with medication errors and, in particular, Never Events. “One day we’ll have one joined up system for healthcare and research,” said Dr Edwards, a consultant in pharmacovigilance and drug safety.

The Pharmaceutical Human Factors and Ergonomics Group will stimulate debate and eliminate blame-culture, providing an impartial forum for open discussion on these critical issues. They will determine what needs to be done to effectively tackle medical errors.

Speaking at the British Pharmacological Society’s annual meeting, Dr Brian Edwards, an expert in safety of medicines, explained that there is no agreed systematic approach involving all parties including the NHS, the pharmaceutical sector, patient groups, lawyers and others, about how we should optimise the way medicines are used to contain the risk of errors at many levels.

Pharmacology is the study of how medicines and other drugs work and are processed by the body. Addressing delegates, Dr Edwards advised, “It is very important for up-and-coming pharmacologists to understand how human and organisational factors contribute to how the knowledge and evidence they create needs to be translated into processes for safe and effective treatments.”

This systematic approach begins early in drug development with drug design and continues through product naming, packaging and labelling.

Some of the names of medicines are similar and therefore it is easier to make mistakes. Drug labelling describes the drug and proper storage,

* Improving medication error incident reporting and learning MHRA and NHS England, March 2014 www.england.nhs.uk/wp-content/ uploads/2014/03/psa-sup-info-med-error.pdf

WWW.EPMMAGAZINE.COM

7

NEWS ANALYSIS

Digital advances revolutionise clinical data Four leaders in oncology research are creating a way to support early decisions in clinical trials, supported by innovative technology

Real time eDecisions in clinical trials The treatment of cancer is moving into a new era. The growing understanding of the genetic and biomarker profiles of tumours makes the possibility of truly personalised medicine treatment tailored to the individual’s tumour molecular profile within our grasp. If this aspiration is to be realised, experts will need to work closely together to harness our evolving knowledge. A more open collaboration will be needed, alongside rapid evolution of genomics and relevant biomarkers, optimisation of clinical trial designs, application and culture, together with providing large volumes of data in a timely and understandable format.

Collaboration Collaboration between many experts is required to optimise our understanding of new cancer treatments, whilst maintaining patients’ safety and assessment of the benefit/risk profile. In addition to the medical staff and scientists, the patients themselves are often the knowledge leaders in their own disease and should have the opportunity to be empowered to speak up and become active partners rather than the silent contributors that they, and we, are used to.

The ‘iDecide’ framework, has been designed to facilitate the partnership and collaboration necessary to capitalise on the scientific advances for the benefit of patients. ‘iDecide’ is a five-year collaboration between four leaders in oncology research; The University of Manchester Institute of Cancer Sciences, The Centre for Cancer Biomarker Sciences, The Christie NHS Foundation Trust Research Division, and AstraZeneca. ‘ iDecide’ aims to create a clinical trial culture which is collaborative and innovative.

Delivering precision medicine

Technological solutions A key component of the ‘iDecide’ framework is access to real-time data to enable real-time decisions to adapt the clinical trial. The two technology solutions to enable real-time eDecisions in clinical trials are REACT and PROACT. REACT (Real-time Analytics for Clinical Trials) is revolutionising clinical data interpretation and visualisation in ongoing clinical studies.

It provides experts with real-time access to integrated clinical trial data such as exposure, safety, efficacy and biomarkers. This enables more informed reasoning, decisions enabled by all available information (eDecisions) and an earlier understanding of the patient benefit-risk trajectory.

PROACT (Patient Reported Opinions About Clinical Tolerability) is an industry-leading system, designed around the ergonomics of the patient, which gives patients a user-friendly way to get involved. They can link to their anchor person at site, and also directly share whatever experiences they have with all relevant experts, including the study sponsor. It’s mobile, quick, and entirely on their own terms: whatever they want to share, whenever they want to share it. In return, patients can receive study-updates from their medical team so that they can learn along with the experts around them.

The sharing and real-time access to this data gives experts a chance to work together to strengthen the link between emerging science and patient-driven needs to inform their treatment decisions enabled by integrated bioinformatics (eDecisions).

Moving forward

‘iDecide’ is a clinical trial bioinformatics research and development framework to support early decisions in clinical trials. It leverages realtime patient information during an ongoing clinical study with the dual purpose of enabling early decisions and supporting effective adaptation of the clinical trial design for the patient’s benefit.

Through the advanced genomics approaches employed by the Manchester Centre for Cancer Biomarker Sciences, ‘iDecide’ aims to 8

improve the availability of molecular selection data to patients and researchers. Using this approach all relevant data can be integrated, maintained and assessed during the study enabling optimal cancer therapies to be matched to patient benefit.

‘IDecide’s vision is to transform the bioinformatics landscape within a clinical trial. The framework and collaboration will continue to evolve and build on this foundation; providing patients access to their own data so that they can become an active participant and collaborator in their own healthcare; developing and enhancing bioinformatics systems. This means that all experts, including patients, can continue to work together as a team, striving to evolve the science of cancer medicine.

WWW.EPMMAGAZINE.COM

9500

IF YOUR BIOLOGIC HAS CHALLENGING PACKAGING NEEDS... ...WEST CAN HELP. SmartDose® Electronic Wearable Injector An easy to use solution for large-volume subcutaneous injection.

NovaPure® Plunger Components Developed using Quality by Design principles to enhance performance in a syringe.

Visit us at Pharmapack in Paris on February 11-12, 2016, Booth #538

www.westpharma.com

9500 EPM SmartDose_NovaPure Ad.indd 1

#9500 0116

12/21/2015 8:32:53 AM

NEWS ANALYSIS

How to stay ahead in drug development For companies working in the drug development services industry understanding marketing trends can be crucial for a competitive edge

T

he Drug Development Services 2015 Marketing Trends Report from SCORR Marketing offers insight into how companies in the industry are meeting their marketing goals. Do companies rely on internal marketing teams or outsource? If they outsource, are they satisfied with their agency’s performance? What marketing goals are the most important?

The results from the survey identify what companies in this industry are doing and pinpoint areas for improvement as well as analysing how these companies are incorporating digital marketing, using social media and determining the best mechanisms for lead generation.

1

10

Most drug development companies seek an agency that has industry experience.

Partnering with a marketing firm with sector knowledge and expertise can help develop a more strategic marketing plan and better differentiate your products and services.

However, your marketing partner needs to be as accountable as your internal team to meet your goals.

2

Recognise the importance of digital marketing. This has become an essential part of the marketing mix, yet many respondents expressed dissatisfaction with the effectiveness of their digital tactics so companies need to develop an integrated marketing plan and identify ways to repurpose content.

WWW.EPMMAGAZINE.COM

3

Measure results. The survey also revealed that many companies make marketing decisions without establishing accountability or measuring results. Assessing how clients perceive you and your competitors should be a key steps in developing a marketing strategy. Also measure the performance of your marketing tactics so you know what is working and what isn’t.

EVENT

Making Pharmaceuticals – ideas, information, answers Making Pharmaceuticals takes place on 26-27 April 2016, at the National Conference Centre, Birmingham, UK. As well as leading suppliers to the pharmaceutical industry, the event offers a strong market focus and conference stream

B. Braun OEM The B2B division of B. Braun

Whatever your role is within the pharma industry, Making Pharmaceuticals aims to offer relevant and targetted content.

The event is designed to bring together all those involved in the product development lifecycle and the commercial manufacturing of pharmaceuticals, providing an strong focus for the different skills, and expertise necessary to deliver consistent products to market.

Featuring a two day conference, with sessions presented by leading industry organisations such as: IPEC Europe, EXCiPACT, ISPE UK, IMECHE, Pharmig, the ICR and Biosimilarz, there will be a focus on the challenges facing the pharmaceutical industry in the UK. Making Pharmaceuticals 2016 offers a conference focused upon excipients and pharmaceutical ingredients, new technology, processing, serialisation, regulatory affairs, data management, GMP and over 80 technical sessions.

B. Braun offers an entire product portfolio for pharmaceutical packaging, drug admixture and delivery to meet the existing challenges in modern infusion therapy. Benefit from a broad range of standard products and contract manufacturing services for medical devices and pharmaceutical solutions.

Standard products Infusion and injection solutions Medical devices for drug admixture Automated infusion pumps Products for venipuncture and injection Products for infection prevention

Customized products and services

Contract manufacturing Product development and private labeling Product combination

The exhibition offers direct access to over 85 leading companies that provide services, products and technology to the pharmaceutical industry. www.makingpharma.com

B. Braun Melsungen AG | OEM Division | www.bbraunoem.com info-europe@bbraunoem.com | www.kitpacking-bbraun.com

WWW.EPMMAGAZINE.COM

11

REGULATORY AFFAIRS

Medical device regulation: An overview Amit Salvi, ELC Group, provides a regulatory overview of medical devices

The medical device industry is a crucial part of the healthcare sector.

The global medical device market is expected to reach $440 billion by 2018, growing at about 4.4% per year. Contrast that with the

EU Clinical Trial Requirements: Regulatory requirements for clinical investigations of medical devices are

prescription drug market, predicted to grow at an annual rate of 2.5%.

different to those for pharmaceuticals, as there is no legal requirement

Established players in this industry include the United States and Western

to demonstrate the efficacy of the device in order to obtain CE marking.

Europe. But industry trends show that Asia and importantly, China are

The objective of the device clinical trials is to demonstrate the safety and

about to play a prominent role in the next few years.

performance (conformity with claims) of a medical device. The stage of a clinical investigation which needs to be satisfactorily completed for CE

The Global Harmonization Task Force classifies medical devices into

marking is most likely Phase II, where evidence of clinical activity of a

class A, B, C and D, with class D representing the highest risk.

drug is sought, rather than Phase III.

U.S. Regulation: Medical devices are regulated under the Federal

The relevant EU legislation addressing the clinical evaluation of medical

Food Drug & Cosmetic Act (FD&C Act) Part 800-1299. Manufacturers

devices is the Medical Device Directive 93/42/EEC, as amended (March

importing medical devices into the USA must designate a United States

2010) and the Active Implantable Medical Device Directive 90/385/

agent, register the establishment, list the device, manufacture according

EEC, as amended (March 2010). This legislation was transposed into

to the quality system requirements and file a Premarket Notification 510

national law in all concerned countries.

(k) or a Premarket Approval. A post-marketing surveillance system is required (21 CFR Part 803). Medical devices are divided into Class

The type and amount of clinical data needed primarily depends on

I, Class II and Class III, where class I devices represent the lowest risk

the specifics of the clinical claims with regard to clinical performance,

and class III devices represent the highest risk. Most Class I devices and

considerations of clinical safety – including determination of undesirable

some Class II devices are exempt from a Premarket Notification 510 (k).

side-effects – and on risk management output, namely determination of

Class II devices generally require a 510 (k) while Class III devices require

residual risks and favorable benefit/risk ratio.

a Premarket Approval.

12

The Conformity Assessment process for active implantable medical devices

EU regulation: Regulation in the EU differs from the U.S., in that

as well as for class III and implantable medical devices requires that a

medical devices bearing a CE mark can be freely marketed across

clinical investigation is undertaken, unless it is duly justified to rely on existing

Europe. Overall, the requirements for obtaining an EU CE mark are

data. Any such justification will have to be based on a proper clinical

more straightforward and less time-consuming than those for a U.S.

evaluation. Depending on clinical claims, risk management outcome, and

FDA approval. The Medical Devices Directives (MDDs) form the

on the results of the clinical evaluation, clinical investigations may also

foundation of Europe’s regulatory framework for medical devices. A

have to be performed for non-implantable medical devices of classes I, IIa

manufacturer that does not have a registered place of business in the

and IIb. Additional clinical investigations may be feasible to corroborate

EU can designate a single authorized representative in the European

the existing clinical evidence with regard to aspects of clinical performance,

Union. Medical devices are divided into class I, class IIa, class IIb and

safety, benefit /risk-ratio, or to determine relative effectiveness and safety

class III, where class I also has the subclasses Sterile and Measuring.

with suitable comparators. Manufacturers have to submit the results from

All medical devices except class I devices require the involvement of a

any clinical trial, but there is no obligation to discuss the design of the study

Notified Body.

with the Notified Body or a regulatory agency prior to the trial.

WWW.EPMMAGAZINE.COM

THE RIGHT SOLUTION

FOR INTEGRATED SOFTGEL DEVELOPMENT AND MANUFACTURING. Pharmaceutical companies throughout the world have come to rely on Capsugel’s state-of-the-art softgel manufacturing capabilities. With three best-in-class manufacturing units, our France-based product development and manufacturing site allows us to produce more than 3 billion softgel and liquid filled capsules for distribution around the globe. Our versatile facility and expertise give us the ability to develop and produce a wide range of pharmaceutical products including highly potent, oxygen and light sensitive compounds. Softgel products containing hormones are produced in a dedicated manufacturing unit.

To find your solution visit www.capsugel.com.

Better medicines through science and engineering.

OPINION

Linked in Michael Acott, Baird’s CMC, specialist health consultancy, explains how supply chain improvements move medicines more efficiently to poor countries

N

eglected tropical diseases (NTDs) are the focus of a global effort to control or eliminate them by 2020. Billions of people are at risk of these diseases, which cause deformities, blindness, incapacitation and life long suffering. But, it’s no good manufacturing and donating huge supplies of treatments for devastating neglected tropical diseases (NTDs) unless you can get them to where they are most needed, quickly and efficiently.

Six multi-national pharmaceutical companies have now come together in the NTD Supply Chain Forum to speed up the increasing drug donations and streamline delivery of medicines to people at risk or suffering from one or more of these diseases in poor and often remote parts of the world. It is a partnership with the World Health Organization (WHO), the Bill & Melinda Gates Foundation, public health organisations and logistics providers.

The pharmaceutical industry donates more than a billion doses of medicines each year across more than 70 countries. The industry effort has also become more focused through the enhanced collaboration of pharmaceutical companies which are more usually commercial competitors. In 2012, they came together with the WHO, public health NGOs and other partners to pool their expertise. They signed the London Declaration on NTDs, committed to increasing donations of medicines and set timelines and objectives, including the control or elimination of 10 neglected tropical diseases by 2020.

The members of the the NTD Supply Chain Forum include six multinational pharmaceutical companies which signed the declaration – Eisai, GSK, Johnson & Johnson, Merck Sharp & Dohme, Merck KGaA, Pfizer and logistics company DHL. It is co-funded by the pharmaceutical companies and the Gates Foundation. They collaborate on logistics, both in terms of direct coordination as well as sharing of best practices.

Some companies donate medicines for the same diseases – sometimes in different countries, sometimes in the same country where medicines are given in combination. They also donate different medicines for different diseases in the same country.

Progress has included improvements in drug production timelines, changes in national drug application mechanisms and better distribution and delivery to destination countries.

“When it comes to countries, programmes are starting to be a lot more integrated. We have a huge interest in trying to deliver some of these medicines at a similar time to a specific country,” said Tijana Duric, who has chaired the NTD Supply Chain Forum since its inception.

“There’s a real sense of collaboration in terms of how and when we deliver,” said Duric, director of supply planning and finances at the Global Health Programmes Unit, GlaxoSmithKline.

The pharmaceutical companies started the forum and have brought in other organisations where they can help, such as on logistics or software development.

Deliveries of several donated medicines are co-ordinated through the DHL “control tower” at the headquarters of its humanitarian operations in Copenhagen. As the control tower also handles shipments for United Nations agencies, government organisations and other NGOs, the staff are familiar with humanitarian supply logistics, and country-specific requirements on issues such as customs regulations.

14

DHL’s involvement has also enabled priority bookings with certain shipping lines, reduced port charges for humanitarian shipments at the point of entry and longer periods for clearance before demurrage charges apply.

With the help of another international organisation, RTI, the forum is also developing a web based management tool for forecasting and planning. This will handle everything from the initial application for drugs from countries to delivering it all the way through the supply chain.

A large part of the supply chain focus has been on what is known as the “first mile” – from manufacture to delivery to a warehouses in the country concerned. This includes manufacturing, packaging, shipment, customs clearance and delivery. Efforts are also underway to improve the “last mile” – from the warehouses to local distribution points and then delivery to small communities in sometimes remote districts.

While the first leg is controlled by the donors, the second is in the hands of national and local governments, communities and NGOs in the country concerned. Work on ‘last mile’ improvements is more difficult, but Duric is optimistic.

“We have achieved tremendous results in our ‘first mile’ collaboration.

As soon as people get in the same room and discuss these things, and share best practices, there is significant change and improvement. We have seen that cascade down, with things being standardised and implemented across companies,” she says.

WWW.EPMMAGAZINE.COM

̈

EPM

e

1.6

107x156

2013

Labeling by Faubel.

CONVINCING QUALITY.

tsubstances? oxic Transferring potent or

Visit us at PHARMAPACK, 10th - 11th February, Stand 613, Paris, France

Müller Containment Valve MCV

– Suitable for EEB 5 (OEL < 1 µg/m3) – Available sizes: DN 100, DN 150, DN 200 and DN 250 – Explosion pressure shock resistant up to +10 bar – Vacuum-tight version down to –1 bar – Explosion-proof to ATEX for Zone 0/20 – Easy-to-wipe flat surfaces – AISI 316 L stainless steel, Hastelloy available on request – GMP-compliant design

Müller GmbH - 79 618 Rheinfelden (Germany) Industrieweg 5 - Phone: +49 (0) 76 23 / 9 69 - 0 - Fax: +49 (0) 76 23 / 9 69 - 69 A company of the Müller group info@mueller-gmbh.com - www.mueller-gmbh.com

secure, hygienic and simple communication

melaphone

visaudio

Clean Rooms Food Industry Hospitals Certified to ISO 14644-1 Level 5

Booklet labels for automatic application Multi-layer labels up to 9 pages Single-layer labels from small lots to high volumes Tamper-evident solutions

Call us now on

UK 01359 233191 Int +44 1359 233191 info@melaphone.co.uk melaphone.co.uk

www.faubel.de

WWW.EPMMAGAZINE.COM 2016-01 EPM.indd 1

15 14.01.2016 15:08:15

COVER STORY

Modern love Modern drugs often consist of combined active ingredients.

Now these can be stored separately in a double chamber cartridge and yet be administered very easily

T

he pharmaceutical industry has made great progress in developing increasingly effective medicines for the chronically ill. These usually have to be injected, some on a weekly basis, others several times a day. This places a burden on patients as well as healthcare systems.

Because of this it makes sense to have the patients perform the injections themselves. This in itself is not a problem; however, many new drugs can only be stored stably in freeze-dried form. Prior to injection, they must be liquefied by using water for injection (WFI) or another diluent. The patient needs two vials with different contents and a syringe. First, the diluent must be drawn into the syringe and injected into the second vial. After shaking it, the drug can be drawn into the syringe again and administered. The risk of error, such as a possible contamination of the substances, increases with the number of steps. In addition, there is the risk that the patient could miss the right mixing ratio or inject the wrong dosage.

Schott has developed a solution for these forms of administration – a double chamber cartridge for pen systems. It contains the two drug components in two consecutive chambers that are separated by a plunger. When the pen lock is turned, the plunger will be pushed to the level of the bypass, and the liquid will flow into the anterior chamber where it will mix with the second component. The reconstituted drug can then be injected without any risk of contamination and in the exact dosage by simply triggering the pen.

“Many new drugs are initially made available as lyophilisates because manufacturers are still looking for a way to store the active ingredients in a stable manner,” says Schott product manager Andrea Wesp. “If they opt for a double chamber, they don’t have to accept any compromises because the components can be stored and protected, reconstituted quite easily and then administered in the safest and most convenient way – four advantages at once.”

Schott double chamber cartridges are used in pens and can combine either liquids with liquids or liquids with medications in powder form. The two chambers are separated by a plunger. When the patient or doctor turns the closure of the pen, the back plunger moves forward and presses the medication against the front plunger up into a passageway that is less than 0.1 millimeters in width. The medications stored in the back chamber can pass through this bypass and enter the front chamber where they can mix. To inject the medication, the patient simply places the pen against his skin and presses the release button.

16

WWW.EPMMAGAZINE.COM

Benefits of a double chamber cartridge The main advantage this approach offers is how easy it is to use. Instead of deploying two containers to store the lyophilisate in one and the diluent in another, double chamber cartridges carry out mixing and application in one go. The pen system allows for higher dosing accuracy and a lower risk of contamination. This translates into much higher safety for patients, as literally a push of a button is all that is needed.

Schott cartridges are compatible with the most commonly used pen systems; therefore pharmaceutical manufacturers do not need to develop these devices on their own.

Quality during the manufacturing process Schott manufactures the double chamber cartridges at its Center of Excellence in Switzerland, and has optimised the production process based on its many years of experience in cartridge manufacturing.

Today, the bypass of the cartridge is created using compressed air during the hot forming process.

This avoids any traces of tools and particles. Moreover, double chamber cartridges are produced without any glass-to-glass contact just like insulin pen cartridges. The aim here is to avoid cosmetic defects.

The cartridges come in standard dimensions, but can also be customized. The length and position of the bypass as well as the edge can be adjusted to meet individual requirements. â&#x20AC;&#x153;The latter is important if a customer wants to fill the drug directly in powder form,â&#x20AC;? says Wesp. Alternatively, the active ingredient can also be filled in liquid form and then be lyophilised inside a freeze dryer.

WWW.EPMMAGAZINE.COM

17

Introducing

We have come together to support all your development needs.

Introducing PCI, a market leader for integrated drug development and commercialization We have combined the expertise of Penn Pharma, Biotec Services International, AndersonBrecon and Packaging Coordinators to create PCI, an integrated pharmaceuticals provider positioned to support your drug needs from molecule to market. With drug manufacturing expertise, global clinical trial services, and commercial services for manufacturing and packaging, PCI supports over 50 product launches per year and medicines destined to over 100 countries around the world.

We invite you to learn more about how partnering with PCI can ensure the success of your next product launch.

Clinical Services Manufacturing | Packaging & Labeling | Global Storage & Distribution

Commercial Services Manufacturing | Packaging | Serialization

Š Copyright 2015 Packaging Coordinators, Inc. All Rights Reserved AndersonBrecon (UK) Limited trading as Packaging Coordinators, Inc. is a company registered in England and Wales with company number 02543975 and VAT registration number GB 549 7026 19 whose registered office is at The Broadgate Tower, Third Floor, 20 Primrose Street, London, EC2A 2RS

www.pciservices.com

Penn Pharma, a PCI company, is a Trading Name of Penn Pharmaceutical Services Limited Registered in England & Wales No. 1331447 Registered Office: Tredegar, Gwent NP22 3AA UK VAT Reg. No. 762 3299 16 Biotec Services International is part of Biotec Worldwide Supplies Group of companies, Registered in Wales NO 3483803. VAT Registration No. GB 108216149.

PCI_GroupAdFINAL.indd 1

9/21/15 10:49 PM

49 PM

OPINION

Agility training Unless the pharmaceutical industry manages product lifecycle data holistically in 2016, companies’ ability to achieve regulatory compliance and maintain speed to market will be compromised, warns Mark Evenepoel, Amplexor Life Sciences

O

f all the challenges facing life sciences organisations in 2016, it is the conflicting priorities of regulatory compliance and global competitive pressure that will be the most demanding.

That’s unless companies find a new, more holistic way to manage their product lifecycle data right across their operations – from R&D to market distribution.

From a regulatory and risk perspective, these requirements absolutely must be met. But companies need to do this in a way that is both efficient and adaptable – as new regulatory requirements will continue to appear and evolve, and not all of these can be predicted in advance.

Without a single, master approach to data, a company’s ability to seize new opportunities will be limited by the substantial administrative burden associated with meeting the growing number of regulatory requirements in each target market. In an aggressive global playing field, success relies on speed and adaptability which is difficult to maintain against a flow of red tape.

Supporting new product strategies

2016 will be a turning point, for a number of reasons. Data silos – so common in pharma due to the global sprawl of companies and the industry’s history of merger and acquisition – are a barrier to agility.

They result in administrative repetition, they incur inaccuracy, and they compromise the ability to deliver correct content quickly to where it’s needed to get a product to market promptly.

Preparing for regulatory requirements – current & future Managing fragmented data systems and processes is expensive.

According to research published by Gens & Associates in April 2015, life sciences organisations that manage their content at a holistic, pan-enterprise level see better ROI than those persisting with standalone projects.

Yet the temptation to approach product data management on a project by project basis remains. New EU legislation requires the implementation of new data standards (Identification of Medicinal Products or IDMP) – designed to enable the unique identification of medicinal products at an international level. To comply, life sciences organisations must develop a method and process for generating global product identifiers, which can then be used for product reconciliation and linking across the entire product supply chain.

Significant investment will be required not only to align key product data across a range of functions, also to pursue operational excellence in R&D and customer safety: the ultimate goal of the new standards.

At the same time, companies must raise their game commercially. The last year has seen considerable strategic change in the life sciences industry, as pharma organisations have sought to realign their value propositions with target customer groups. Selling solutions rather than product features is not only more appealing to customers, it also presents additional cross-selling opportunities.

But again, all of this is difficult to manage optimally with a single set of supporting data, and robust processes that will enable this new way of promoting products. New strategies must involve strengthening collaboration and information-sharing - both among internal functions and with external partners - to create a global supply ecosystem that is more closely integrated, responsive and focused on the patient. And this must begin with a single, centralised approach to product lifecycle data management.

Developing a plan Rather than bemoan the issues, companies need to take assertive action so that 2016 is a transformational year. The first objective must be to design a clear roadmap for a centralised approach to produce lifecycle data management. Even where legacy systems are an important consideration, organisations should work towards a centralised strategy for master data and product lifecycle information management. This could be achieved virtually, for example, but external experts can be called upon to help with the ‘how’.

There is light at the end of the tunnel. Pharma companies are already sitting on most of the data they need to achieve their goals (albeit not necessarily in a structured format yet), because of the regulatory demand to capture and document high levels of detail. The opportunity now is to unlock, structure and amalgamate this data so that it can be exploited to competitive advantage.

WWW.EPMMAGAZINE.COM

19

THE YEAR AHEAD

What lies ahead?

What’s hot for 2016? Lu Rahman asks key industry players for their pharma trends for the coming year?

C

ertain topics within pharmaceutical manufacture remain year on year. Companies continue to address issues of quality, counterfeiting and adherence while innovating with formulation and ingredients – all this while maintaining a competitive edge and offering a customer-focussed service. Innovation is

always vital in this global industry - last year we saw the digital health sector impacting on pharmaceuticals and this trends looks set to have increased significance in 2016.

Wearable devices allowing the self-administration of drugs at home are becoming increasingly commonplace.

Add to this the development of the first digital medicine product which addresses issues surrounding adherence, and the things are continuing to look very exciting in this space.

As always, the industry’s key players have their own opinions on the trends that will be big news in 2016. Elliott Berger VP global marketing & strategy at Catalent Pharma Solutions says: “2016 will see continued pressure to make pharma companies’ R&D functions more productive and efficient, combined with the need to progress the best drug candidates faster, and with lower risk of failure. As a result, we envisage the growing importance of quickly selecting the most appropriate drug delivery technologies and driving integrated development processes to get better treatments though trials, and ultimately to patients.”

Reflecting this market outlook, the company has introduced the OptiForm Solution Suite to help develop and deliver optimised dose forms of API molecules using superior delivery platforms, and providing optimal animal PK materials in just twelve weeks.

20

WWW.EPMMAGAZINE.COM

Regulation The issue of regulation is always on the agenda in the pharmaceutical sector. An increasingly stringent regulatory environment places on-going pressure upon pharmaceutical manufacturers globally.

Analytical and bioanalytical contract solutions provider SGS Life Science Services has had a productive 2015. It spent the summer planning the opening of a new bio/pharmaceutical quality control laboratory at Villeneuve La Garenne, replacing the existing Clichy facility.

The new facility supports biologics development in the French market, reducing sample processing times through increased operational efficiency. It also offers services for the growing biopharmaceutical pipeline with capabilities for mycoplasma tests and amino acid analysis.

The company also completed construction of its, China, cGMP chemistry and biotechnology testing laboratories.

Ferdinand Dabu, marketing director, SGS Life Science Services, recognises the importance of regulation in the company’s work. Looking ahead to what the coming year holds, he says: “A recurring response from our lab network involved an increasingly tough regulatory environment. Specifically, stricter regulations from local authorities are pushing manufacturers in Asia to meet international standards. Additionally, we anticipate continued interest in elemental impurities as USP <232><233> are now in force for new products (2016 for EP 2.4.20 and 5.20) and will be required for existing products in late 2018 (2017 for EP).

Next, with many biosimilars in development, expect to see more making it to market with the evolution of the regulatory environment in the US.” Dabu also foresees the trend of drug/delivery device combinations to continue, shifting the paradigm in how these products are tested.

Counterfeiting Counterfeiting is a serious issue within the pharma sector, costing it significant amounts of money annually.

Any drug or medicine that contains the wrong or ineffective ingredients can have a harmful effect on an individual’s safety.

Richard Nemesi, global marketing manager for pharmaceutical and medical devices, Videojet Technologies, told EPM last year that, “counterfeit drugs cost the pharmaceutical industry billions of dollars each year and can erode priceless commodities – brand reputation and consumer trust”.

According to Nemesi, due to the Falsified Medicines Directive (FMD) deadlines in 2018, large pharmaceutical manufacturers are already implementing serialisation capabilities into production. He sees this trend continuing into the coming year. He also expects to see smaller organisations such as contract packagers start putting the wheels in motion to serialise their packaging lines.

“The Delegated Acts have been adopted by the European Commission and are expected to be published early 2016. What is perfectly clear is that a coding solution for FMD will need to feature robust data management, seamless integration into manufacturing equipment and high resolution print capability to convey information throughout the supply chain,” he states.

Ian Lemon, global product director, health & personal care, Essentra, agrees on the industry’s need to counteract counterfeiting.

“With the continuing rise of illegal counterfeit drugs and the upcoming Falsified Medicines Directive, expect an increased focus on security and anti-counterfeiting in 2016. Key focus areas will be track-and-trace – using identification numbers to monitor a drug’s journey from supply chain to consumer distribution – and tamper verification in a number of forms, such as labels, cartons, tear-tapes and seals.”

Lemon believes that in order to achieve the highest level of protection, however, companies should use a multi-layered approach incorporating serialisation, tamper verification features and overt/ covert authentication solutions.

Peter Sheppard, Genpact, is also clear on the importance of serialisation.

“Product serialisation and tracking capabilities will bring new insights to the commercial side and attack working capital. The HCP experience will improve through a 360-degree engagement across R&D, medical and finance. Integrated, personalised interactions with patients, consumers and customers will deliver better care and breakthrough insights for both R&D and commercial.

“The winners will build lean processes designed from the perspective of patient and customer outcomes, unconstrained by internal boundaries. Implementation success will depend on robust back-office integration.”

WWW.EPMMAGAZINE.COM

21

Bormed™ Because we care

Reliable plastic solutions for the safety of patients Borealis and Borouge are leading suppliers of innovative plastic solutions that add value for all stakeholders in the healthcare value chain – from pharmaceutical company to patient.

With more than 30 years of experience, we enable customers to meet their need for high-quality, lightweight and aesthetic products. We focus on delivering excellence by working in line with the principles of Commitment, Service and Conformance.

Our portfolio of Bormed™ products is the result of our continuing dedication to your industry.

Our Bormed™ portfolio of polyolefin solutions offers superior technical performance for medical devices, pharmaceuticals

and diagnostic packaging. We guarantee the security of our supply and provide technical support tailored to the specific and stringent requirements of the market. Our service specialists cover 55 countries worldwide, so we can offer global service, while ensuring fast and reliable delivery.

We are dedicated to the quality of your products – for the safety of patients – because we care.

For more information visit: www.borealisbecausewecare.com

Visit Borealis and Borouge at Pharmapack Europe in Paris from February 10-11, stand 2015, hall 5.2.

European Pharmaceutical Manufacturer_01_02_240x340_18_01_2016_high.indd 1

18.01.16 12:13

Adherence Globally, adherence is an ongoing issue for pharmaceutical companies and individuals. Last year the FDA accepted the first digital medicine product combining a drug with an ingestible sensor to create a combination product, Abilify. One of the key benefits of this technology is its ability to aid adherence.

William Carson, president and CEO of Otsuka Pharmaceutical Development & Commercialization, the makers of Abilify, said: “Today, patients suffering from severe mental illnesses struggle with adhering to or communicating with their healthcare teams about their medication regimen, which can greatly impact outcomes and disease progression.

“We believe this new digital medicine could revolutionise the way adherence is measured and fulfill a serious unmet medical need in this population.”

In 2003, the World Health Organization (WHO), indicated that ‘Increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments’ (“Adherence to long-term therapies: evidence for action”, 2003).

According to Jérôme Empereur, CEO, Stiplastics, in light of the WHO recommendation, and at a time when outpatient services are becoming the preferred option and patients are being encouraged to take more responsibility, it will be increasingly important to find ways of managing and monitoring patients’ treatment at home.

“Indeed, it is estimated that in developed countries, one patient in two with a chronic disease fails to follow their treatment correctly (forgetting, taking their medication late and so on). Pharmaceutical laboratories are fully aware of this and will be relying increasingly on the development of the internet of things and the technologies associated with it to develop smarter and more effective packaging to benefit both patients and stakeholders involved in health.

“The combination of electronics and plastic – the plastronics already widely used in the automotive industry – offers the potential for multiple solutions, such as an alarm to indicate when a dose should be taken, the box unlocking at the right time, feeding information back to a third party to confirm that the patient has taken their medication, etc.

Smart thinking: According to Jérôme Empereur, Stiplastics, 2016 will mark the arrival of smart packaging for the pharmaceutical industry

“Connected pill dispensers undergoing clinical trials are generating data that could also be used to adjust treatment based on observance, to administer the ideal dose required to achieve the best possible result.”

According to Empereur, 2016 will mark the arrival of smart packaging for the pharmaceutical industry.

Quality Alex Bunting, I Holland marketing, recognises the continuing importance of quality in the pharmaceutical sector and the company’s reaction to this.

“With the pharmaceutical industry continuing to grow and flourish, our focus for 2016 is to keep delivering the highest quality tooling and technical service to our customers.

We are celebrating our 70th anniversary this year and during the past seven decades I Holland has worked hard to become leaders in tableting science and provide customers with the best in technical support through a number of methods including new innovations and solutions to tackle common tabletting problems. We will continue to do this through investment in research and development which will help the pharmaceutical industry’s requirement for tablet production to be fast, efficient and fault free.”

WWW.EPMMAGAZINE.COM

12:13

23

1 - 2 JUNE 2016 BASEL MESSE BASEL, SWITZERLAND

CONNECT AT CHEMSPEC LEARN | MEET | SHARE

PUT THE DATES IN YOUR DIARY NOW Over the past 30 years Chemspec Europe has developed into a multi-faceted networking event, shaped by input from visitors and exhibitors. Chemspec Europe 2016 will be showcasing a series of FREE TO ATTEND conferences, seminars and workshops held over both days of the show and dedicated to the fine, custom and speciality chemicals industry. Put the dates in your diary to make sure you donâ&#x20AC;&#x2122;t miss it.

Organised by

A member of

In association with

Incorporating

Official Media Partner

Magazine

www.chemspeceurope.com EPM_240x340+3mm_en.indd 1

20/01/2016 17:29

Formulation Last year Dr Julien Meissonnier, Pharmaceutical Softgel Europe, Catalent looked at lipid-based formulations to increase the bioavailability of poorly soluble drugs.

He highlighted how poor solubility remains an ongoing challenge in formulation development. The number of poorly soluble compounds is estimated to be 40% of molecules on the market, however, more than 70% of drugs in development are classified as poorly soluble.

According to Zak Yusoff, senior product development manager SP Scientific, Lyophilised Antibody Drug Conjugate (ADC) and highly concentrated protein formulation will continue to gain momentum in 2016 with more products approval expected.

He adds: “In order to meet global medicinal needs, the pharmaceutical industry continues its quest for robust and fast lyophilisation processes to bring these products to the end users faster and safer. To meet this demand, adoption of existing technology such as controlled ice nucleation technology with the goal to improve product quality attributes and use of other process analytical technology tools will become more prevalent. Companies are investing more in education for their scientists to realize these goals.”

Jan Vertommen, senior director, product development & manufacturing, Capsugel, believes that innovation in improving the bioavailability of compounds will continue to be a central challenge for the pharmaceutical industry in the year ahead.

“Today, more than 60% of compounds in early development exhibit low bioavailability, and many compounds already marketed exhibit bioavailability challenges and can benefit from an optimised formulation. We are leveraging our science and engineering expertise to design and develop more effective drug products based on such an optimised formulation approach for poorly bioavailable compounds. Through our extensive range of bioavailability enhancement technologies – including lipid-based formulations delivered via liquid-filled hard capsules and soft gels, solid amorphous dispersions based on spray-dried dispersion or hot-melt extrusion technology, micronisation, and specialised nanocrystal technologies – we see numerous opportunities to help bring better medicines to market.”

Julien Meissonieer What’s the solution: Last year Dr Julien Meissonnier, Catalent highlighted how poor solubility remains an ongoing challenge in formulation development

Continuous manufacturing In 2015 the European Consortium on Continuous Pharmaceutical Manufacturing (ECCPM), looked at issues surrounding continuous processing. It discussed how the FDA has endorsed the transition towards continuous manufacturing (CM) as a way to shorten the supply chain, increase agility and flexibility of development and manufacturing and to improve product quality through real time process control.

Making good: Dale Natoli, Natoli Engineering Company says continuous manufacturing will be significant in 2016

Dale Natoli, president Natoli Engineering Company is aware of the significance that continuous manufacturing has and will have on the market.

“Continuous manufacturing will continue to be explored and slowly implemented by the pharmaceutical industry. Significant advances in understanding the rheological and size properties of powders and the impact on solid oral dosage forms that these properties impart to the quality of a drug product has helped advance the likelihood of adoption.

The interaction of tablet compression tooling with the powder can be a critical dimension of the manufacturing process. Punches and dies can be designed to complement the formulation’s properties, thereby providing trouble-free manufacturing and improving tablet quality,” he says.

WWW.EPMMAGAZINE.COM

17:29

25

FIVE facts about

PERSONALISED MEDICINE

1

Personalised – or precision – medicine is designed to avoid the ‘one size fits all’ approach to treatment by taking into account genetics, lifestyle and environment. It has been hailed as the future of healthcare and in areas such as oncology, this approach has become particularly important – trastuzumab (Herceptin) for breast cancer is one example. This drug is said to be more effective fighting cancer cells that have an extra copy of a certain gene as well as an increased level of the protein corresponding to that gene.

personalised medicine

2

What is personalised medicine?

There are several FDA-approved treatments in this field which are tailored towards an individual’s genetic makeup or the genetic profile of a tumour.

Profit centre

Personalised medicine is big business. According to a report by global law firm Reed Smith, 94% of life science companies will be planning an acquisition this year – more than two thirds of life science companies will be targeting this market when they do.

3

Return on investment While the popularity of and focus on broad application pharmaceuticals will remain strong, many industry experts say the returns on personalised medicine – despite the smaller market – look like they will be higher.

5

Who’s Who The Who’s Who in personalised medicine is already looking impressive with names like GE Healthcare, Illuminia and Bayer Healthcare coming early to the party.

In 2003 GE Electric (GE) announced plans to purchase Amersham, a British medical diagnostics and bioscience company, for $9.5 billion. At the time, GE’s chairman and CEO Jeffery Immelt said: “We’re seeing the emergence of molecular and personalised medicine … Amersham puts us in the driver’s seat.”

4

Due to the high calibre of pharmaceutical manufacturers entering this area, industry rivalry will be strong so the coming year could be very exciting indeed.

Growth expected

Figures back up the potential in this market with industry statistics (Grand View Research) saying the segment will grow to a nearly £1.76 ($2.5 billion) industry by 2022.

According to the European Union (EU), personalised medicine ‘should be seen as an evolution of medicine, rather than a revolution’.

In the last nine years the EU has committed more than €1bn into health research funding for the development of personalised medicine via its Seventh Framework Program for Research and Technological Innovation.

WWW.EPMMAGAZINE.COM

27

FORMULATION

Q

Making a success 2015 was a stellar year for Hovione. Roger Viney, senior business director, off-patent API, outlines some of the key achievements leading to the company’s success What were the highs for Hovione in 2015?

2015 has been a record year for the company. Our CAGR over the last five years has been 11% and this shows no signs of slowing. Our financial year does not finish until March 2016, however we are on track to record growth compared with the previous year of 15%. Our business is split roughly 50/50 between contract manufacturing services and off-patent APIs and both business segments are growing at a similar rate.

&A

Hovione recently acquired a formulation plant. How will this affect business going forward? What gains do you envisage?

We bought a formulation plant adjacent to our existing manufacturing facilities in Portugal. It will be part of our contract manufacturing business allowing Hovione to offer customers an integrated service from API to formulated dose that expedites the development process. This is particularly attuned with the need for speed in breakthrough therapies. The facility will be able to provide oral solid dosages and precision capsule filing. It will be capable of handling potent products up to Safebridge category 3a. It will focus on development projects of 0.5 to 4 million tablets or capsules per year.

How do you see the pharma sector at the moment – its strengths and weaknesses?

Medicine use is forecast to grow by a quarter in the next five years with half of that growth being in the emerging economies. The FDA approved 41 new drugs in 2014 of which over a third were first-in-class and 41% are used to treat rare or orphan diseases, so innovation is alive and well. These new drugs will one day become generic giving a further boost to the industry. It is also important to note that of the new approvals 75% were small molecules so chemical synthesis still has a bright future. The global economic situation has improved and the pharma industry is well funded. Most innovation is coming from smaller companies and they have ready access to capital. This should mean a continuing flow of new drugs at least in the short term. There have been a large number of mergers driven by large US companies having significant profits held abroad and by the positive response of the stock market to these deals, particularly in the generic sector. The peak of this activity may now have passed and the question will be if these mergers ultimately meet the industry’s need for both innovation and affordable medicines.

In the API manufacturing industry it is clear that the quality suppliers are experiencing favourable market conditions. The outsourcing of manufacturing has continued and many new drugs are being developed by small companies who have no intention of making their own APIs. In the generic API sector there has been a “flight to quality” caused by increased regulatory scrutiny and problems with some Indian and Chinese suppliers that have forced pharma companies to reassess their approach to risk. This has led to many API manufacturers struggling to keep up with demand. In the short term this tightness in supply is likely to continue but there have been numerous announcements of new capacity being installed.

28

WWW.EPMMAGAZINE.COM

Added assets: Hovione’s new formulation facility will be able to provide oral solid dosages and precision capsule filing Photo Hovione

What do you see as the key focal points for 2016 for both Hovione and the wider pharma industry?

The biggest issue for all of us is the increased antibiotic resistance that threatens to take our ability to fight infections back to the 1940s.

There are initiatives such as the GAIN Act in the US that are designed to promote the development of new anti-microbial drugs. The whole industry will have to pull together to ensure the antibiotic void is filled as fast as possible.

contract manufacturing businesses. In our off-patent API business we have started a project to manufacture our actives in at least two geographically separate sites within the group thus giving our customers increased security of supply. Finally, we are using our unrivalled knowledge of particle engineering to grow our range of off-patent APIs with bespoke particle properties for inhalation applications. The new products include glycopyrolate, fluticasone furoate, vilanterol, indacaterol and aclidinium.

Hovione is a privately-owned company and has the advantage of having a long term and consistent strategy which is to focus on providing differentiated products and services to the pharma industry. We have already announced that in 2016 we will make significant investments in our facilities in the US and Portugal.

This not only includes the addition of contract manufacturing of drug product as mentioned above, but also an increase in the capacity and capability of our API and particle engineering

WWW.EPMMAGAZINE.COM

Growth spurt: Hovione has already announced that in 2016 it will make significant investments in its facilities in the US and Portugal. Photo: Hovione

29

BOHLE TECHNOLOGY CENTER

Continuous Manufacturing Starts Here • Standard of excellence from Bohle and nine partners • Pharma systems and expertise from one source • Complete hardware and software integration • Measuring, monitoring and controlling continuous production under excellent conditions • Comprehensive process support and service

.

ur success

as for yo Smart ide Our partners:

www.lbbohle.com

Rhinitis Allergic . .O.P.D C & a Asthm

The metering valve

technology platform that is continuously improving Includes novel proprietary COCe Sealing Gasket:

DF30

Technology Platform

Compatible with EtOH containing and dry formulations Ultra clean and pure material (lowest extractable level) Excellent leakage barrier and moisture absorption properties

ur bo to

Visi

at

oth

#612

February 10 -11,

2016

30

aptar.com/pharma WWW.EPMMAGAZINE.COM

FORMULATION

Green flag Issues of sustainability are becoming increasingly significant for pharmaceutical manufacturers. How far are they committed to changing the way their business affects the environment asks Lu Rahman?

S

ustainability has become an integral part of the manufacturing process for the majority of industries and the pharmaceutical sector is no different. Eco credentials span a range of procedures.

Maximising energy efficiency, keeping a close eye on a carbon footprint and examining the efficiency within the supply chain, are just some of the examples of the way pharmaceutical manufacturers are reducing their company’s effect on the environment and in the process, reducing costs.

Initiatives in green chemistry and solvent reduction have also become key focal points for the modern pharmaceutical manufacturer.

Globally pharmaceuticals contribute a significant proportion of healthcare associated greenhouse gas (GHG) emissions. According to the Sustainable Development Unit (SDU) – which has been working with a range of companies to find ways to reduce the carbon footprint of pharmaceuticals – in 2012 21% of GHG emissions of the UK’s NHS were attributable to pharmaceuticals. In 2012 the SDU formed an international alliance that created the first document providing a method for consistently calculating the carbon footprint of pharmaceuticals and medical devices.

The move towards a more sustainable industry has been significant.

In 2013 the Association of the British Pharmaceutical Industry (ABPI) collaborated with the Carbon Trust to help pharmaceutical companies quickly estimate the carbon footprint of tablet medicines distributed in blister packs.

The tool, a first for the pharmaceutical sector, was developed in collaboration with the Carbon Trust and funded by the ABPI, AstraZeneca, GlaxoSmithKline, Janssen-(J&J), Eli Lilly, and Pfizer. Not only did it help companies work out the carbon footprint of tablet medicines in blister packs simply but it also demonstrated the industry’s commitment to help reduce its impact on the environment through sustainable practices including management of carbon footprints.

A range of data was incorporated into the model which covered carbon emissions for Active Pharmaceutical Ingredients (APIs), transport and distribution, formulation and packaging, retail and use phase and finally, the disposal of the packaging.

Stephen Whitehead, former chief executive, ABPI: “The development of this tool forms part of the ABPI’s commitment to help its members to identify carbon hot-spots for products and areas for potential carbon footprint reduction. These may include raw materials manufacture, selection of materials and transport.”

Hugh Jones, managing director, advisory at The Carbon Trust commented: "There is an increasing awareness among pharmaceutical companies that emissions outside their direct control can represent opportunities to improve cost efficiencies and reduce emissions.

Mounting pressure to demonstrate environment impacts of products to customers is also a key driver for action across the sector. The launch of the foot printing tool is a really positive step towards helping these companies to understand the embodied carbon of different drugs and shows what can be achieved through sector-wide collaboration.”

Greener energy generation Using resources more efficiently and complying with regulatory frameworks are increasingly important in pharmaceutical manufacture.

Using cleaner forms of energy generation is another way to aid the sustainability process.

Earlier this month FuelCell Energy revealed that it is to install a combined heat and power (CHP) system at Pfizer’s Connecticut site. The aim is for energy costs to be reduced as well as allowing Pfizer to hit clean air initiatives. The system will work independently from the grid supplying power to the company’s 160 acre facility. Importantly it also means that Pfizer will be able to achieve its commitment to sustainability through low carbon and efficient energy generation.

Pfizer is transparent in its sustainability goals. By the end of 2020 the company has pledged to reduce it greenhouse gas emission by 20%, reduce the amount of waste disposal by 15% and reduce its water withdrawal by 5%. The company’s green aims don’t end there as it has specified that 100% of its key suppliers support its code of conduct and manage their environmental impacts through effective sustainability programs. It also specifies that 90% of its key suppliers have themselves set in place goals for greenhouse gas emissions, waste disposal and water withdrawal.

‘Admirable goals’ Last year in The Guardian, Alison Moodie described the way in which Dow Chemical Company had “set itself a sweeping series of sustainability goals, which it claims will not merely reduce its own impact but also drive environmentally responsible practices at other companies.”

WWW.EPMMAGAZINE.COM

31

EXHIBITION & CONFERENCE 10 &11 FEBRUARY 2016 PARIS EXPO, PORTE DE VERSAILLES, HALL 5

Register to attend Using media code MP1299

Join us at Pharmapack, your hub for Innovation, Networking & Education in Pharmaceutical Packaging and Drug Delivery Technologies This annual 2-day event features: • 370 exhibitors, 3,000+ attendees • Conference, Symposium, Workshops, Learning Lab and Networking Breakfasts, detailing the latest market trends • Innovation Gallery showcasing innovative, recently launched exhibitor products

http://bit.ly/1mBbdXT

• The Pharmapack Awards ceremony celebrating the most innovative new solutions • The Pharmapack Global Meetings program, helping you to select and connect with likeminded people

INDUSTRY ARTICLES, NEWS, WHITEPAPERS & EVENT PROGRAMME ON WWW.PHARMAPACKEUROPE.COM

These goals included the creation of ‘breakthrough innovations’, ‘valuing nature’ and engaging employees for impact’ with the aim of both improving lives and delivering cost savings. In fact, what is setting Dow Chemical Co apart is its pledge to improve the lives of 1 billion people while making savings of $1bn.

Neil Hawkins, Dow’s corporate vice president and chief sustainability officer, told the newspaper: “We’re really focusing on taking the science and technology of Dow and devoting our efforts to finding new ways of doing business that will help companies collectively change our role in society.”

The measures were praised by sustainability experts. Moodie wrote: “Sheila Bonini, CEO of The Sustainability Consortium, called the plan ‘admirable’, while David Levine, co-founder and CEO of the American Sustainable Business Council, called the goals ‘encouraging’.

With the focus often on drug development, new formulations and even merger and acquisitions, the sustainability decisions pharmaceutical companies are making can often be overlooked. But with companies such as Dow Chemical Co making such grand promises, it seems that many may be taking the lead, providing examples to help improve the environment and our lives.

Similarly, GSK has an equally transparent procedure when it comes to sustainability. Its CEO, Sir Andrew Witty has been reported as saying: “How we operate is just as important to us as delivering financial performance.”

The company says its longterm goal is to be carbon-neutral by 2050. In order to reduce its water impact it is exploring ways to reduce water use and to halve its operational waste by 2020.

GSK is doing this by adopting what it says are four simple steps to ‘eliminate, reuse, recycle and generate energy from waste’. It also says it is applying green chemistry principles to the manufacture of its products in a bid to diminish and / or remove hazardous chemicals from its drug development and discovery process.

With this aim in mind, GSK set up a Green Chemistry Performance Unit (CPU), in 2012 to look into the way it can replace hazardous chemicals with lower-impact ones.

Recognise and reward Each year Recipharm recognises work being carried out in the environmental field with its International Environnmental Award. It says the aim of this accolade is to ‘encourage and inspire best practice and innovation in order to promote good examples and to encourage environmental dialogue within the pharmaceutical sector’. Recent winners have included Ludwig Metz, associate director environmental, Health & Safety, Bristol–Myers Squibb, for his example of how sustainability activities and competence can inspire his own company as well as universities, pharmacies and organisations to make positive sustainable changes.

Development of cleaner systems Last year the University of Manchester announced that researchers had developed a novel biocatalytic system that potentially allows for the efficient and environmentally benign production of organic chemical compounds. The findings were published in the journal Science.

Amines are key intermediates for the synthesis of a plethora of chemical compounds at industrial scale and are used in the production of active pharmaceutical ingredients, among others. However, these requisite amines are scarce in nature.

Although various methods have been developed in the past decade to produce these specialised high-value chemicals, they require long chemical synthetic routes involving complex reaction steps with potentially toxic side-products and waste streams.

Researchers at the Manchester Institute of Biotechnology (MIB), in collaboration with BASF, have developed a system that replaces these methods with a clean biocatalytic route whereby high value amines are synthesised from low cost alcohols by the coupling of two enzymes, namely an ADH (alcohol dehydrogenase) and an AmDH (amine dehydrogenase) in the presence of ammonia. Normally these enzymes would require excessive amounts of expensive co-factors to drive the individual reactions but these co-factors are recycled through the coupling of ADH and AmDH in a one-pot reaction whose sole byproduct is water.

This new route offers potential economic as well as environmental benefits and will provide opportunities for industrial exploitation, including the synthesis of new chemical libraries that will support industrial and academic drug discovery programmes.

Developing the use of biocatalysts within the chemical manufacturing industry could lead to efficient production routes to high yields of complex chemicals, whilst using less energy and generating less waste than conventional processes.

Professor Nicholas Turner explains the importance of this process: “This fundamental research builds on the MIB’s expertise in biocatalysis and forms the basis for the development of new applications in the sustainable manufacture of fine and speciality chemicals. The development of this new generation of biocatalysts should lead to economic and environmental improvements in the manufacture of a range of chemicals, including pharmaceuticals and polymers. It also offers the possibility of circumventing current industrial processes which are reliant on scarce natural resources.”

The road to a sustainable industry is definitely long but thanks to the combined efforts of industry and academia, the sector is showing a positive approach to sustainability as it sees the value in protecting the environment, its reputation, society and its profits.

WWW.EPMMAGAZINE.COM

33

Your fast track through regulatory challenges.

The new Emprove® program.

Does the constantly changing regulatory landscape sometimes feel like a maze?

The new Emprove® program provides the answers you need, with a portfolio of 400 pharma raw and starting materials backed by information to support your qualification, risk assessment, and process optimization activities.

• Portfolio of products to address different risk levels • Elemental Impurity Information (ICH Q3D) • Online access to all dossiers in the new Emprove® Suite Take advantage of this process accelerating combination of high-quality products and targeted insight.

We help you find the fast track through the maze.

Find out how at: www.merckmillipore.com/emprove

Merck Millipore is a business of Merck Millipore, the M mark and Emprove are registered trademarks of Merck KGaA, Darmstadt, Germany. © 2015 Merck KGaA, Darmstadt, Germany. All rights reserved.

151006_Merck_Emprove_240x340_EPM_Merck_RZ_v1.indd 4

09.10.15 10:01

PURIFICATION

Gaining perspective Amit, Karpe, 3M explains how it is challenging the traditional clarification process. Using its expertise and technology platforms, the company is approaching it with a different perspective

M

onoclonal antibody manufacturing is a complex process which includes numerous stages. The process consists of cell culture, cell harvest, protein-A capture, virus inactivation, product concentration, sterile filtration and filling. Service providers push for innovation in the processes downstream of protein-A column. The same cannot be said for upstream process.

Clarification process prior to protein-A column consists of conventional methods eg centrifugation. These clarification methods are not always reliable and often difficult to scale-up. They sometimes break down and cause increased down time and production delays. Another pain point is efficiency â&#x20AC;&#x201C; these methods offer little or no removal of host cell DNA. Thus, impurities like host cell DNA in the form of chromatin, host cell proteins (HCP) and any microbial contaminants are loaded on to the protein-A column. As a result, the impurities bind to the protein-A column, this non-specific binding takes away the efficiency from the chromatographic column. These impurities are also difficult to get rid of so the cleaning protocol requires the use of harmful chemicals, posing risk to the media in the column but also to the personnel performing the cleaning procedure. This eventually results in column fade and a reduced number of runs of the expensive protein-A column.

At 3M we challenge this traditional clarification process. With our expertise and the 46 3M technology platforms, we are able to approach a problem from different perspectives. The Emphaze range offers a new platform of efficiency, purity and economics and has led us to create an exciting product called Emphaze AEX Hybrid Purifier. The anionic exchange (AEX) part of the new Emphaze AEX Hybrid Purifier offers chromatographic purification with its four layers of Q functional non-woven hydrogel media. Hybrid nature of the product refers to

Triple assets: According to Amit Karpe, 3M, its Emphaze range offers a new platform of efficiency, purity and economics

the constitution of the product; it is a novel product which combines chromatographic separation along with a downstream 0.2 micron membrane filter. The hybrid purifier has been designed from the ground up; we translated the industry needs to deliver this next generation purifying device.

Emphaze AEX Hybrid Purifier is able to reduce host cell DNA by 4 log reduction value (LRV) which translates to 99.99% reduction.

HCP reduction of up to 35%, Bioburden reduction of 6 LRV which corresponds to 99.9999% reduction. This product has the potential to replace centrifugation, which is cumbersome and not always reliable. When used in conjunction with a depth filter Emphaze AEX Hybrid Purifier can offer unsurpassed quality of fluid to load on protein-A column.

As the majority of host cell DNA is removed prior to protein-A column, the latter is free to do its main function: capture mAbs. We have encouraging results which show an increase in its performance.

Because there is no large amount of DNA/chromatin attached to the column, the cleaning protocols can use less concentrated chemicals post use. This helps to extend protein-A columnâ&#x20AC;&#x2122;s life, another benefit of the new 3M hybrid purifier.

As Emphaze AEX Hybrid Purifier provides early purification, it opens new avenues to downscale existing processes post protein-A columns you use. We have seen AEX column being made redundant in certain cases!

We have launched purifiers ready for R&D, pilot scale and full production scale. Our team of application engineers are ready to work with you and provide you all the necessary information and products to set-up process trials optimised for your needs.

Diagram highlights scalability

WWW.EPMMAGAZINE.COM

10:01

35

PHARMAPACK

A la mode Updates on the latest market trends in drug delivery and packaging will be on offer at this year’s Pharmapack

T

his year’s Pharmapack Europe – which takes plave on 10-11 February at Paris Expo Porte de Versailles – has identified several key trends that it says pharma and companies operating in drug delivery and packaging, must address in 2016.

The annual event will take in Paris on 10-11 February where industry analysts, executives and companies will gather to learn and discuss the latest issues affecting the industry.

A key issue for 2016 will be the ongoing implementation of track and trace technologies, and the impending European falsified medicines directive. Experts will discuss the implications of the pan-European authentication scheme, its impact on contract manufacturers, OEMs and pharma companies. Speakers will include Craig Stobie, Domino; Romulo Leon, Mettler Toledo PCE; Michel Bullen, Optel Vision; Rick Seibert, Sharp Packaging Solutions and Michael Gaub, Pester.

The European standard EN 16679, has recently come into effect and provides guidance for the application, use and checking of tamper verification features to the packaging of medicinal products. By 2018, all prescription medicine will be required to include a tamper verification feature (TVF). Pharma is now at a crossroads, say the organisers of the event and manufacturers across Europe have to decide which TVF to choose before the looming deadline.

smaller and smarter combination products that will speed-up time to market by examining the manufacturing scale-up strategy, concurrent with the development process.

Technologies and packaging that can improve patient adherence will remain a key growth area and several sessions will run at Pharmapack across the design process for patient friendly packs and how new innovations alongside social media are helping drive crucial competitive advantages. In oral solids, the discussion for the last 30 years has been rigid versus flexible solutions – essentially bottles versus blisters. But in 2016, companies will be seeking better packaging options for pharmaceutical doses.

Communication is key Moreover, the drive for packaging to communicate with patient and healthcare professionals is growing rapidly – whether driven by regulatory agencies (serialisation and traceability) or consumer groups. The next hotbed of potential innovations is set to be flexible packaging for variable dosage forms, in line with the rise in personalised medicine.

Ultimately, we may see packaging that has the scope to communicate, or be involved more directly, in the relationship between consumer and physician. But who will be the industry trailblazers and can disruptive players like Apple and Google help to build new ecosystems that revolutionise this status quo?

Outsourcing growth Human factors engineering Combination products will also be a key area for 2016, with the integration of human factors engineering (HFE), design for manufacturing (DFM) and design for assembly (DFA) seen as the foundations for the development of this product class. There will be an emergence of

Outsourcing is continuing to accelerate with new prototypes and innovations emerging rapidly from the contract services sector itself.

This has huge implications not only in terms of regulation challenges and changes but also in terms of skills migration from pharma into the supply chain. The conference will conclude

WWW.EPMMAGAZINE.COM

with a roundtable on ‘emerging technologies and innovation forecast’.

Steven Kaufman, global business development lead, Bespak, commented: “Pharmapack Europe provides an excellent opportunity for attendees and exhibitors to engage with current and prospective business partners in packaging and drug delivery. It’s a vital reference point of new business strategies, thought leadership, and innovation that will shape the industry over the next year.”

Innovation gallery The Innovation Gallery at Pharmapack Europe 2016 will showcase the advances in packaging intelligence – such as new material, primary and secondary packaging, delivery, labelling, leaflets, anti-counterfeiting technologies, and traceability – that will underpin the next generation of delivery technologies in 2016 and beyond.

“The year ahead is extremely exciting for the pharma packaging and drug delivery industry, with new strategies across patient packaging and combination products, as well as outsourcing helping to bring drugs to market faster. Our conference platform and innovation galleries have identified the crucial breakthroughs that will revolutionise not only how pharma and supply partners work together, but also how these technologies will be essential in transforming the patient experience. In the last few years, packaging and delivery have become an even more essential part of a drug’s regulatory approval process, adherence and efficacy – especially as the use of personalised care and cost effective generics increase. I would encourage anyone looking to stay ahead of market trends and meet new innovative partners to attend Pharmapack,” said Anne Schumacher, event director, Pharmapack.

37

CONTAMINATION CONTROL SPECIALISTS

PROTECTING CRITICAL ENVIRONMENTS SINCE 1966

SCIENTIFICALLY PROVEN TO COLLECT AND RETAIN UP TO 99.9% OF CONTAMINATION AND CROSS CONTAMINATON

Dycem has been helping protect controlled areas from the risk of contamination since 1966. Discover today what Dycem can do for your facility.

Contact us today for a free site survey.

WHERE TO USE DYCEM At entrances to critical areas to prevent the ingress of contamination All exits to prevent contamination leaving the critical area In corridors to prevent cross-contamination between areas Inside critical areas, adjacent to critical processes and sensitive products Inside airlocks, gowning rooms, warehouses and product transfer rooms Inside modular cleanrooms

e: contact@dycem.com

| t: + 44 (0) 117 9559 921

www.dycem-cc.com

l d s

CONTAINMENT

Isolated case The Dec Group explains how its isolation technology has been put to use in a pharmaceutical environment

A

customer active in the hormone production recently searched an appropriate solution for grinding material and clean packaging after the filtering and drying process.

A range of requirements was required. It was important that the system offered a safe barrier between the operator and the active drug substance to provide both operator and product protection. The system needed to be designed for multi product use for OEB5 category potent compounds. The isolator had to be A range of requirements designed for the automated discharge was required. It was and manual heel removal, milling and important that the system dispensing of product discharge from filter drier. It also had to enable manual offered a safe barrier sampling to be achieved via the filter dryer between the operator and sampling port which is integral to the the active drug substance discharge hatch and be designed to mill to provide both operator and pack other products introduced to the isolator via a RTP Rapid Transfer Port. and product protection The customer also specified that the equipment should be able to operate in an inert atmosphere during product discharge and be able to allow the process plant to be cleaned in place.

“

the lower chamber through another continuous liner/bag connection.

The material is therefore double packed and sealed to achieve this very high containment level before leaving the enclosure in the drums.

A roller system allows for easy drum manipulation.

The isolator and process equipment cleaning is essentially designed for wash in place, using provided spray balls and spray guns.

The isolator is installed within an Atex classified area and is controlled via a PLC with operator interface via a touch screen HMI. Due to the hazardous area classification the main control panel is installed in the non-hazardous client technical area.

The SMEPAC verified < 25 ng/m3 containment system conforms to cGMP standards and was fabricated in accordance with pharmaceutical standards for secondary manufacture with a fully welded design and rounded corners providing smooth interior surfaces.

”

Dec’s solution is based around a three-chamber isolator to provide a high containment environment during the automated discharge by means of an agitator, milling and dispensing of product from a filter dryer. The isolator has been designed to offer a DEL (Design Exposure Limit) <50 ng/m³ of time weighted average and an STEL (Short Term Exposure Limit) <25 ng/m3 for operations lasting less than two hours.

The upper chamber, designed to receive and mill the discharged product, features the filter dryer outlet port enabling a smooth and free-flowing transition from the filter dryer into the isolator, a product chute into the mill with a dedicated tool for manual heel removal through the dryer’s discharge port , the cone mill as well as the weigh system indicator panel. It also includes a DEC MPTS sampling system for taking samples of the milled material. Glove-guards prevent operator entrapment when the filter drier agitator is running.

The middle chamber houses a weigh platform and a DEC continuous liner pack-off head for primary containment.

Both middle and upper chambers include Rapid Transfer Ports (RTP) for product and sample transfers into and out of the containment system, independent isolator differential pressure controls and HEPA filtration systems. They are designed to operate at a negative pressure and with nitrogen purging during processing. Once the target weight is reached and the endless liner is sealed, they pass into

WWW.EPMMAGAZINE.COM

Triple whammy: Dec’s solution is based around a three-chamber isolator to provide a high containment environment

39

CLEANROOMS

Clean living How Cherwell Laboratories has been assisting Portsmouth Pharmaceutical Manufacturing Unit (PMU) in its environmental monitoring (EM) programme for over 20 years

P

ortsmouth PMU specialises in the aseptic preparation of pharmaceuticals and parenteral nutrition, cytotoxics and patientcontrolled analgesia in a variety of administration devices. With two aseptic rooms, eight isolators, two preparation rooms and a checking and labelling area; an extensive environmental monitoring programme (incorporating both active and passive air sampling, as well as contact plates) is in place to ensure the environment is free from microbial contamination.

Reliability, ease-of-use and sampling speed were all key considerations in Portsmouth’s selection process for a microbial air sampler. With a sampling rate of 180 litres per minute, the SAS Super 180 unit is the fastest sampler available, completing a cubic metre in less than six minutes – this saves on staff time and minimises disruption. In addition, the SAS is unique since it uses more readily available and therefore less expensive, contact plates as the consumable. Furthermore, its portability allows PMU to easily conduct environmental monitoring across its various locations.

Julie Bowden, QA releasing officer, Portsmouth PMU commented: “When we were looking to buy a new unit, we didn’t look at any other air samplers on the market. We only considered Cherwell due to our positive experience of the product and their excellent customer service.

Cherwell is always very accommodating and deals with any queries straight away, we don’t have to be passed on to someone else.”

The reliability and robustness of SAS air sampling equipment, combined with Cherwell’s technical expertise, were also key factors in Portsmouth’s decision to continue using SAS units. In addition to the newly purchased

unit, PMU still uses another SAS Super 180 unit 12 years after the initial purchase, confirming the lifetime value of the units. This has been supported by Cherwell’s customer focused calibration service – operated by the company’s own engineering department based in its Bicester facility – this also ensures a rapid turnaround time. Calibrations can also be arranged to fit in with customer requirements, further minimising downtime and inconvenience.

“Cherwell makes it easy for us to arrange recalibration at a time that suits us and the turnaround time is very quick,” said Nicola Lightfoot, QC technician, Portsmouth PMU. She added, “If any repairs are required, a quotation is always provided before the work is carried out and we are kept informed of progress.”

The longstanding relationship between Portsmouth PMU and Cherwell has been based on providing the most appropriate product to fit the required application, alongside a flexible and reliable service. In fact, in addition to the portable SAS Super 180 units, PMU also uses SAS Super Isolator units for dedicated EM within isolators; it has also received regular and flexible delivery of Redipor prepared culture media since 2006. Cherwell’s focus on customer support, high quality products and technical advice are all valued by Portsmouth PMU, who knows its specific requests will be dealt with efficiently and effectively.

Through understanding the increasing regulatory requirements placed on pharmacy manufacturing units within the UK, Cherwell has been able to assist Portsmouth PMU in meeting these obligations. This has only been possible by having good knowledge of the industry sector and providing products and services that are fit for purpose.

WWW.EPMMAGAZINE.COM

41

DOSAGE

Soft sell Gelita outlines the role of pharmaceutical gelatin and its growing importance in capsules and fortified gummies

Pharmaceutical gelatin offers manufacturers of drugs and supplements a versatile excipient that has been used in the pharmaceutical industry for decades. A key application is capsule production; approximately 90% of all pharmaceutical gelatin produced is processed into this widely used drug dosage form.

Gelita manufactures and supplies gelatin for all types of capsules. In many ways, because of the numerous advantages of the dosage format, the gelatin capsule is the ideal delivery vehicle for a variety of medicines and/or therapeutic agents. With Gelita RXL, the company claims that it has managed to overcome cross-linking issues in capsules. On top of this, more recently gelatin-based delivery system has risen in popularity among grown-ups – fortified gummies.

Advantages of capsules Gelatin capsules are among the most popular dosage forms for drugs, over-the-counter (OTC) products and food supplements. Consumers appreciate the smooth surface of the capsules making them easy to swallow — an important aspect of patient compliance. Gelatin itself is highly compatible with other ingredients, is non-allergenic and comprises proteins that are easily digested in the gastrointestinal tract, which facilitates the release and absorption of active ingredients.

Gelatin capsules protect sensitive ingredients such as fish oil from oxygen, light, contamination and/or microbial growth. Although hard capsules are primarily used for powder applications, soft capsules are the preferred dosage form for liquid, paste-like or oil-based fills. Unlike any other type of capsules, soft gelatin versions are hermetically sealed and airtight, thereby masking any unpleasant taste or odour of the fills.

This also makes the softgel format very tamper-evident while providing high dose accuracy.

42

One of the most widely recognised benefits of soft gelatin capsules is enhanced nutrient bioavailability. By encapsulating liquid- and pastefill formulations with very low particle sizes, soft gel capsules provide opportunities to improve the absorption of poorly soluble drugs. Consumers not only benefit from a quicker onset of action, the higher bioavailability also translates into the ability to reduce the required amount of active ingredients.

Another key strength of softgels is their versatility. In general, soft shell capsules release their contents in five–15 minutes. However, by altering the formulation of the gelatin capsule shell, the specific effect, timing and duration can be modified and adapted to consumer needs.

Plus, gelatin capsules show endless opportunities in terms of size, colour, shape or printing options, allowing for customised products and unique presentations.

Capsule technology innovation Despite the advantages of gelatin capsules, certain types of reactive fillings and extreme storage conditions — such as high temperature and humidity — may cause the gelatin in the capsule to react and cross-link.

With time, soft capsules become increasingly less soluble, which results in longer dissolution times in the GI tract and the slower release of the fills.

Now, the Gelita Pharmaceutical Competence Team has developed a new technology: Gelita RXL (Reduced Cross-Linking) that adds extra value to gelatin capsules. It significantly reduces the amount of crosslinking, thus enhancing the dissolution properties of the capsules as well as improving their shelf-life at high temperature and humidity. The new technology even allows the pharmaceutical industry to explore new capsule fillings and expand their distribution into regions that are exceptionally hot and humid.

WWW.EPMMAGAZINE.COM

Various attempts by the pharmaceutical industry to reduce cross-linking with additives have only been partially successful. Gelita, however, followed another route it established that small, highly mobile gelatin molecules are, under suitable conditions, able to block the effects of the larger molecules — similar to interfering with the interaction between a key and its lock. The Gelita solution can be described as a sort of “self-defence mechanism,” brought about by a combination of large and small molecules. More precisely, Gelita has increased the concentration of collagen peptides that naturally occur in gelatin. These collagen peptides react with the gelatin and block it, making it no longer available for self-cross-linking reactions and/or reactions with other reactive groups, such as traces of aldehydes or chromium, alumina and copper, within the capsule.

Purity and safety Gelita RXL is pure pharmaceutical-grade gelatin, free from any nongelatin additives, which complies with all existing regulations. It meets all product specifications for gelatin capsule applications and is the ideal product for use with problematic fills or where normal gelatin cannot be used because of cross-linking. The use of Gelita RXL can also accelerate product development; it reduces the risk that a capsule formulation, once developed, will later be discovered to fail storage requirements.

However, the production of fortified gummies is much more than just adding vitamins and minerals; it’s also about meeting the needs of elderly people, for example, by incorporating higher levels of important nutrients or even active ingredients. Today, protein-enhanced fruit gums or collagen peptide-based gummy applications for improved skin, joint or bone health are becoming increasingly relevant. The challenge with these product examples is to incorporate a sufficient amount into the gummies, using established gummy manufacturing process and equipment, without changing the overall taste and texture.

Fortified gummies: not just for kids Fortified gummies first made their appearance in the US in the late 1990s as an alternative delivery method or system for children’s vitamins and minerals. Traditionally administered as medicinal syrups or chalky and unpleasant chewable tablets, consumer compliance was often reduced by undesirable, inconvenient and bad tasting products.

As such, the industry and young consumers alike quickly embraced these novel confectionery-like vitamins. As a result, manufacturers are now expanding the category into the adult world as well.

With the rising importance of issues such as convenience, dosage control and consumer acceptance, fortified gummies now dominate the US paediatric vitamin and mineral category by an overwhelming margin. Further market growth is expected as adults have become aware, and are now demanding, the same benefits for themselves. To drive innovation and demonstrate the potential of this young category, Gelita’s technical experts are constantly working on new fortified gummy concepts. From sugar reduced and tooth-friendly variants to solutions with minerals, omega-3s or fibres — the potential to create tailored products that match individual consumer needs is huge.

“

Various attempts by the pharmaceutical industry to reduce cross-linking with additives have only been partially successful. Gelita, however, followed another route

WWW.EPMMAGAZINE.COM

”

43

PHARMINTECH 2016.

N E V E R S T O P I N N O VAT I O N .

BOLOGNA, 13 - 15 APRIL 2016 WWW.PHARMINTECH.COM

In conjunction with:

With the patronage of: UCIMA

Italian Packaging Machinery Manufacturers Association

Organised by:

With the contribution of:

PACKAGING

In short...

Sean Egan provides a bite-size view of Nelipak Healthcare Packaging

Nelipak Healthcare Packaging is … … a full-service global provider of custom thermoformed packaging that provides superior protection for pharmaceuticals and medical devices.

We fulfil customers’ healthcare packaging needs including: concept, design, development, prototype and production tooling, validation, and commercial product output, including AVS and sealing machines.

What makes you stand out?

Nelipak is a strategic packaging partner that’s 100% focused on the healthcare market. We offer medical trays and blisters, surgical procedure trays, pharmaceutical handling trays, custom built sealing machines, total packaging solutions and other value added services.

As well as using best-in-class manufacturing processes, we apply a combination of freehand design capabilities and technology to help our customers develop better products for end-user needs and to proactively innovate to industry trends.

Something you are proud of …

Our global presence means our team is highly accessible and can provide innovation and quality to our customers wherever they are located.

We have facilities in the US, the Netherlands, Ireland and Costa Rica with more than 500 employees worldwide. We are also totally focused on the healthcare market and the needs of medical and pharmaceutical customers. All Nelipak sites are equipped with cleanroom capabilities and certified to ISO 13485 standards.

What’s great about this industry?

As you can guess, our passion is packaging! We are excited by new opportunities we are pioneering to bring change to all parts of the product lifecycle and how improve the way users interact with packaging.

We have a team of healthcare-focused designers and engineers who apply a combination of freehand design capabilities with technology including sketching, solid works simulation software, 3D printing to support our customers in developing packaging that offers an improved level of user experience.

The ability to proactively innovate even at the earliest stages of development by applying a thorough understanding of industry trends and end-user needs and challenges helps create optimised packaging that can better serve its purpose, reduce waste and even minimise risk factors when used in the operating room.

What’s going to happen in 2016?

We’re seeing more and more pharma and medtech companies merging to deliver more targeted treatments for a range of conditions.

As a result, I think we’ll continue to see an increase in drug combination devices over the next 12 months and beyond.

“

Our global presence means our team is highly accessible and can provide innovation and quality to our customers wherever they are located.

WWW.EPMMAGAZINE.COM

” 45

28 SEPT - 29 SEPT 2016

EXHIBIT NOW

TESTING

Joint forces: Kaye’s measurement expertise was combined with Fedegari’s application and process knowledge

“

The Kaye Validator AVS ‘is a revolutionary development in wired technology that will carry validation into the future’

”

Put to the test Kaye tests validator at Fedegari Technology Last year Fedegari Technology invited the Kaye team to its R&D

Building upon the Validator 2000, the AVS improves measurement

laboratory last October for testing sessions with the Kaye Advanced

accuracy, flexibility and speed. Its data management and redundancy

Validation System (AVS) on Fedegari sterilisers. Process equipment and

enhances data integrity and security. The validation console provides

R&D personnel were available at Fedegari’s centre

a dedicated validation interface with enhanced

to assist in testing the reliability and performances

connectivity (wifi, docking), touch screen interface,

of the new system.

“Compared to the previous equipment, the new generation of Kaye Validators shows a significant evolution: an intuitive technology with easy-touse features that improve the MMI such as touch screen, wifi and system connectivity. It is always a pleasure to work with strategic partners like Kaye.

This was a great opportunity for both companies

“

improved data management via asset centric concept and improved reporting and analytics.

This was a great opportunity for both companies to share knowledge and combine experiences to enhance innovation

to share our knowledge and combine experiences to enhance innovation,” said Marco Ruggeri, R&D lab senior engineer at Fedegari Group.

”

“Implementing this breakthrough concept was a natural step that Kaye has shared not only with customers, but with competent and well recognised partners in the industry since the very early stage of the R&D progress. Fedegari Group as a long-term strategic partner supported our development by working with us to test the AVS utilising its sterilisation systems in Fedegari centre in

Sellersville, USA and Albuzzano, Italy. Combining Kaye’s measurement According to Monika Knüppel, marketing communications manager at

expertise with Fedegari’s application and process knowledge was

Amphenol Advanced Sensors, the Kaye Validator AVS ‘is a revolutionary

a perfect alignment to stimulate innovation in thermal validation

development in wired technology that will carry validation into the future’.

technology”, said Frank Kies, general manager at Kaye.

WWW.EPMMAGAZINE.COM

47

HEALTH & SAFETY

Safe houses Kevin Spiess from BS&B Safety Systems discusses solutions for protecting pharmaceutical facilities against dust explosions

U

K pharmaceutical manufacturing is a substantial contributor to the economy. In 2013 it accounted for 9% of the UK’s total manufacture output, with the total pharmaceutical sector turning over about £60bn. It is an economic asset worth protecting and it’s on the rise.

Yet, in spite of the explosion risk management requirements set out in DSEAR (Dangerous Substances and Explosive Atmospheres Regulations 2002) and ATEX European regulations, the dangers of dust explosions in the pharmaceutical manufacturing sector remain just outside of the safety spotlight. Devastating dust explosions have occurred in pharmaceutical facilities around the world, destroying equipment, injuring or taking lives and halting businesses. It’s not a risk worth taking.

Why is dust dangerous?

Elements of an explosion The ‘explosion triangle’ consists of three main elements required to cause a dust explosion: ignition, fuel and oxygen. When one of these elements is interrupted or controlled, an explosion can be prevented.

Active pharmaceutical ingredients (APIs) have the potential to release explosive pressure between 9-10 bar and often act as the fuel for an explosion in a pharmaceutical facility. However, the additives used in conjunction with the APIs also have explosive capability, such as starch or lactose. Consequently, the pharmaceutical manufacturing industry needs to manage explosive dust potential of two kinds: • materials that may cause a deflagration •materials that have detonation potential (which require much more rigorous controls and fail-safes to prevent ignition and detonation.)

“

The most common cause of ignition in the pharmaceutical industry is electrostatic discharge; this occurs during mixing, pouring or sieving processes. Coupled with a higher than normal oxygen concentration in the process equipment and the presence of a highly combustible API, the explosive trinity is complete.

During the handling, storage and processing of pharmaceutical raw materials, the Devastating dust explosions explosion risk of bulk powders is always have occurred in pharmaceutical present. Powders can form dust clouds that facilities around the world, linger in the atmosphere acting as a fuel for destroying equipment, injuring a primary explosion that may be ignited by the smallest of sparks. Suspended dust can or taking lives and halting ignite and burn rapidly causing a secondary businesses. It’s not a risk How to protect against explosion – this is where property and worth taking. dust explosions personnel are subject to substantial risk of harm. If such an explosion occurs in a While some pharmaceutical raw materials confined space, such as a storage vessel, have a lower sensitivity or explosivity reaction or a compounder, then a subsequent rise in explosive pressure can to an ignition source, others have more sensitive reaction parameters. literally have devastating consequences.

Dust testing is always recommended to identify three key performance

”

This was clearly illustrated in 2003 when a major pharmaceutical facility in the US was ripped apart by a chain of propagated dust explosions. This accident claimed six lives and injured 36 members of staff on site. Investigations concluded that powdered polyethylene was the culprit and the ignition originated in processing equipment that used this substance to coat rubber strips. For years, several inches of polyethylene dust had accumulated in the facility’s roof spaces pumped through the ventilation systems, just waiting for the right spark to set it off. It was also surmised that there was an inadequate assessment of the dangers that the dusts posed to make mitigating provisions.

48

characteristics of organic dusts, which in turn influence explosion protection equipment design as well as their application: • The first measures maximum pressure of a dust explosion (Pmax in bar) • The second identifies the speed of the rise in explosive pressure (KSt in m/sec) • The third measures Minimum Ignition Energy (MIE) Dusts differ in characteristics and therefore performance. At BS&B we believe that explosion protection solutions depend on good risk assessment and understanding. All dust hazard projects should start with dust testing. In this way an explosion protection expert can

WWW.EPMMAGAZINE.COM

make an informed safety recommendation for the facility involved.

There are basic explosion safety methodologies which, if correctly applied, effectively mitigate dust explosion risk according to the specialised process needs in the pharmaceutical industry:

Good housekeeping There’s no substitute for diligently cleaning a process facility. An explosion risk can be caused by the build-up of deposits of combustible dust which may accumulate on surfaces in the processing facility.

Accumulated dust may be disturbed by a primary explosion in the process equipment and result in a more severe secondary explosion.

The Health and Safety Executive (HSE) in the UK, recommends that as well as a rigorous cleaning regime, the elimination of high-level horizontal surfaces is preferable, e.g. by use of sloping surfaces to minimise dust accumulation.

Particularly in the pharmaceutical industry, the dissipation of any electrostatic ignition sources by bonding and grounding of equipment is recommended.

Chemical Suppression Systems

Flameless venting In the worst case, should an explosion actually occur inside a process or storage vessel containing combustible materials, a rapid rise in pressure can result putting staff and equipment at risk. Explosion vents are the preferred passive method to relieve such explosive pressure however it is not always practical or safe to vent the pressure and flame to a particular area.

The most advanced flameless vents intercept, quench and retain all burning materials, preventing them from expelling into the atmosphere.

They are particularly useful for dust collectors, bins and bucket elevators.

A process shutdown can also be activated to limit the intake of additional fuel to other process areas.

Chemical isolation systems

“

Particularly in the pharmaceutical industry, the dissipation of any electrostatic ignition sources by bonding and grounding of equipment is recommended.

By stopping a deflagration at the outset, further explosive damage is immediately interrupted and contained. In the pharmaceutical industry where the raw materials are often costly, depend on highly sanitised handling and have a high Kst value, explosion risk becomes a serious business risk. The contamination or destruction of such valuable raw materials by propagating explosion could result in significant economic loss – an undesirable commercial position to be in.

Advanced chemical suppression systems such as the BS&B System V, are designed to detect the start of an explosion (point of ignition) and deliver dry, inert chemical extinguishing agents into a developing internal deflagration. For the handling of pharmaceutical materials that are subject to deflagration (as opposed to detonation) these suppression and isolation systems can be activated by various means, whether triggered by pressure, optical or vent sensors. A possible deflagration travelling through ducts, piping and connected equipment is quickly and efficiently extinguished, thereby preventing any spreading explosion damage.

”

While pharmaceutical process equipment can be constructed to withstand an explosive pressure of 10 bar, the design isn’t usually designed to isolate an explosion should it occur, hence opening the risk to further explosive propagation. Explosion isolation is designed to prevent any kind of deflagration from spreading to other parts of process equipment. There are two methods of isolation:

Passive Isolation: does not require detectors, or control and indicating equipment. These may be arrestor mesh, rotary valves, lock valves, rotary screws, flap valves or diversion valves.

Active Isolation: Activated by detectors and a control and indicating equipment, which are parts of the system, such as pinch valves, chemical Isolation or fast acting valves.

All the above are well used methods to safely control dust ignition and explosions. However, any pharmaceutical dust explosion risk would always warrant further attention.

Protecting against dust explosions requires due diligence, which informs appropriate preventative measures. To do anything less would invite disaster because just one spark could destroy lives and livelihoods, not just on site but along a vital supply chain.

WWW.EPMMAGAZINE.COM

49

CHEMICAL REACTION It’s important to keep on top of the latest services, companies and individuals.

EPM’s Chemical Reaction highlights a technology or business we think would be worth your while keeping in the mix ...

Bug’s life Philippe Villain-Guillot, Nosopharm, highlights how the company is countering multi-drug antimicrobial resistance and explains how partnering with the company is an opportunity for the pharmaceutical businesses to grow their antibacterial pipeline Who are you and what do you do?

Nosopharm is an innovative young drug discovery biotechnology company. Its mission is to address the unmet medical need of bacterial multidrug resistance to antibiotics through the discovery and development of novel first-in-class antibacterial molecules.

The company was founded in 2009 and works in partnership with biopharmaceutical companies to tackle antibiotic resistance in hospital-acquired Gramnegative infections.

We are developing a novel class of broad spectrum antibacterials, the Odilorhabdins, discovered consecutively to the screening of an original microbial bioresource. This novel class is based on a new chemical scaffold with a new mode of action.

What have you focussed on recently?

The company’s recent focus has been on developing its anti-infective drug discovery platform.

The platform is based on the medicinal chemistry of Odilorhabdins, a novel class of antibiotics discovered by the company. This novel class has a very high potential to cure life-threatening multiresistant hospital-acquired infections and targets the most concerning multidrug-resistant Gram-negative pathogens: Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa and Acinetobacter baumannii.

These bacterial pathogens are responsible for 49% of hospital-acquired infections in the EU. In December, 2015, Nosopharm was selected to join ENABLE (European Gram-negative Antibacterial Engine), an Innovative Medicines Initiative project working to advance the development of potential antibiotics against multidrug resistant Gram-negative infections.

This £73.8m project aims to identify at least three antibacterial lead molecules with promising antibacterial activity, two antibacterial clinical candidate molecules and to enter at least one compound into preclinical and Phase 1 clinical studies.

Nosopharm will bring NOSO-95179 to the project, a first-in-class antibiotic for the treatment of multidrugresistant hospital-acquired infections.

50

Q & A

What is your latest service/innovation?

We have developed expertise in the medicinal chemistry of Odilorhabdin, the new class of antibiotics to which NOSO-95179 belongs.

It was discovered consecutively to the lead optimisation of NOSO-95, the first molecule of the new class of Odilorhabdin antibiotics and is a first-generation Odilorhabdin targeting the Carbapenem-resistant Enterobacteriaceae in hospital-acquired infections (KPC, NDM, OXA-48).

It also inhibits bacterial translation with a new mode of action and shows clear in vitro antibacterial activity against multidrug-resistant clinical isolates (eg NDM-1), along with in vivo efficacy in different murine infection models and good tolerability.

As no cross-resistance with currently used antibiotics was observed, this underpins its potential for treating those infections originating in hospitals that endanger patients’ lives.

How can you benefit the pharmaceutical sector?

Hospital pathogens with multiple antibiotic resistances are responsible for at least 380,000 infections and 25,000 directly related deaths per year in the European Union.

From a global perspective, antimicrobial resistance could kill up to 10m people every year by 2050.

High development costs, market competition and low return on investment have caused large pharmaceuticals to disinvest in antibacterial drug discovery and development.

The lack of new antibacterials brought to market also reflects a failure of discovery, as commercially viable compounds with anti-Gram-negative activity have not been found.

That is why many governments and public health authorities are proposing strong new incentives to drive more investment from pharmaceutical companies into the antibiotic field.

WWW.EPMMAGAZINE.COM

Nigel Theobald

Partnering with Nosopharm is an opportunity for the pharmaceutical companies to grow their antibacterial pipeline, in order to re-arm the antibiotic arsenal for the treatment of very concerning resistant Gram-negative infections.

What are your future plans?

Nosopharm will be supported by ENABLE through the next stages of development with access to significant technical expertise and financial support.

The company plans to complete a Phase 1 clinical trial of NOSO-95179, with ENABLE funding 75% of internal R&D costs while the program is active.

During the project, the company will also participate in collaborative research with ENABLE’s expert partners across Europe.

Nosopharm is also working on the development of 2ndgeneration Odilorhabdins with extended spectrum of antibacterial activity.

Nosopharm aims to raise £4m in 2016 with venture-capital funds to complete the financing of its development plan.

DEC_

DEC_EPM_240x340+3_11-2015 09.11.15 14:20 Seite 1

Are your plants ready

to swiftly respond to changing markets and production needs, reliably provide top quality drugs while meeting regulatory compliance?

We can help you to have them.

www.dec-group.net

Powder Handling Excellence

Worldwide Solutions Provider

Now and for the future.

At Natoli Engineering Co., weâ&#x20AC;&#x2122;re proud to engineer punches and dies of superior quality, but we also provide all the technical knowledge and support equipment that you need.

We have built an outstanding reputation for quality service and support and we are driven to exceed our own high standards for performance. Find out more at natoli.com.