The future for pharma

The pharma industry will be strongly affected by the Brexit-related move of the European Medicines Agency to Amsterdam. Nor will Brexit release the industry from compliance with the FMD (Falsified Medicines Directive), aimed at reducing the number of falsified medicines infiltrating the European pharmaceutical supply chain.
While most of the major multinationals are FMD-ready, some smaller manufacturers are yet to make the necessary changes to their operations.

The FMD has hung over the industry for some years. Delays and amendments have meant that previous deadlines have come and gone, lulling some manufacturers into a false sense of security. However, the final implementation date of February this year is upon us and has caught some companies unawares.

According to Richard Pether, Director of coding and marking specialist Rotech, the pharmaceutical supply chain is vast and can be divided into three main sub-groups: large multinationals, parallel importers and SMEs. The FMD is set to affect each of them differently. As might be expected, the large multinationals are well-prepared for the FMD.

The future is far less bright for the so-called parallel importers (PIs). Traditionally, these low profile European firms have operated under the radar, re-labelling and sometimes rebranding EU medicines to sell to the UK market. The FMD will significantly hinder this business model. Buying tablets in Portugal, for example, re-issuing them with an English label and distributing them in the UK will cause alarm bells to ring. Under the FMD, the original manufacturer will have already registered those tablets in Portugal with a unique serial number. Changing the label will alter this registration and pharmacists will be unable to re-dispense the drugs. For PIs to remain compliant, they would need to re-certify each medicine for the new country it will be dispensed in (providing the original manufacturer allows this). The cost and hassle involved may well prove prohibitive and could force many PIs out of the market altogether.

The third and final sub-group are the small and medium-sized pharmaceutical manufacturers. A core requirement of the FMD legislation is the serialisation of individual pharmaceutical packs, via unique codes encrypted in machine-readable 2D data matrix codes. Besides a randomised unique serial number, these codes will be required to carry a manufacturer product code, expiry date and batch number.

SMEs must make some simple changes to ensure compliance. Rotech is reporting an uplift in enquiries for its RF Compliance coder. This can pre-code packaging prior to filling. Unlike some of the expensive and complex online methods better suited to big pharma, this is an affordable, easy-to-operate, stand-alone system that doesn’t interfere with production or compromise line efficiency and is particularly suited to smaller and even manual packaging lines. An integrated camera automatically inspects the data matrix code, text and Pharmacode, ensuring each pack is fully FMD-compliant.

Packaging challenges

Nonetheless, the European drug delivery and healthcare packaging industry is set for significant growth, as Pharmapack Europe welcomed a record 410 exhibiting companies and nearly 5,500 attendees from 75 countries.

Staged at Paris’ Porte de Versailles in early February, the show saw ‘patient-centricity’ emerging as a central theme. A range of new technologies were showcased, from child-resistant pumps and anti-tampering labels to connected and dual delivery devices, disposable autoinjectors and Augmented Reality apps for smartphones.
The conference agenda explored major industry challenges that lie ahead, including how to lower development costs whilst increasing sustainability. Gregor Anderson, Managing Director, Pharmacentric Solutions, suggested that “we could potentially further improve sustainability in device design and sourcing by working earlier with suppliers, so they can engineer out costs and environmental impact.” For example, harnessing the consumer’s growing environmental conscience and asking them to return inhalers to a pharmacy after use for recycling could “deliver tremendous results when factoring in just how many inhalers are disposed of each year”.

Another green approach discussed at the event was replacing PVC in secondary packaging, and Yves Steffen, Head of Packaging & Devices in Biological Technical Development and Manufacturing at Novartis, expects an industry-wide change to a ‘plastic neutral’ position.

But several of the sustainability panel’s experts also forewarned that primary packaging will remain a challenge, as it needs stability testing, which takes a long time to develop and implement. In particular, Guilhem Rousselet, Global Packaging & Serialization – Industrial Affairs at Sanofi added “there is just not yet any industry solution to replace PVC as the material of choice – we are still some way off this”.

AI for healthcare

While small companies face FMD challenges, it is also the small startup companies that are breaking ground in developing AI-assisted products for healthcare.
Consulting firm Frost & Sullivan has predicted a compound annual growth rate in the healthcare AI market of 40 per cent through 2021, largely because AI has the potential to improve healthcare outcomes by 30 to 40 per cent while halving treatment costs. Global Market Insights predicted an increase in the healthcare AI market value from $760 million in 2016 to $10 billion in 2024. Startups around the world will be pivotal in bringing these predictions to reality.

A recent report by CB Insights shows that healthcare artificial intelligence (AI) startups have raised $4.3 billion since 2013, topping all other industries. Kolabtree, the online platform for freelance scientists, has released an infographic highlighting startups that have developed innovative AI-assisted products that are advancing healthcare.

Many of the AI-assisted healthcare products developed by startups are now being used in homes, hospitals and clinics. Kolabtree has illustrated how these products are used to improve drug discovery, diagnosis, treatment and service provision.

“The big corporations often lack the research capabilities to develop AI-assisted products in-house, which is why many have partnered with startups in this sector,” commented Ashmita Das, CEO of Kolabtree. “For example, pharmaceutical giant Merck works with Atomwise, a startup in the US that uses deep learning to shorten the drug discovery process, while GSK has entered into a partnership with a startup called Insilico Medicine, which uses AI to discover new biologic drugs.”

Particle beams in 3D printing

Precision engineering company Reliance Precision is working with the University of Huddersfield to develop intricate, high-strength components for medical implants and the aerospace industry, products that could be made more speedily and economically by harnessing the potential of particle beams during additive manufacturing (AM). Two projects under the auspices of Professor Jaap Van Den Berg, who specialises in ion beam technology, have earned funding from the official body, Innovate UK.

Electron beam additive manufacturing (EBAM) machines will enable much wider adoption of this form of 3D printing, in which metal powder is placed under a vacuum and fused together by heat from a high-energy electron beam. It is a technique that enables the production of highly complex components, building them up layer by layer.

The first Innovate UK-funded project is named RAMP-UP, which stands for Reliable Additive Manufacturing technology offering higher Productivity and Performance).  This has now concluded and led to patented technology that greatly reduces the need for pre-sintering. The goal for a second two-year programme called INSPIRE is to make pre-sintering completely unnecessary and enable metal powder to be recycled and reused by an EBAM system.

Labelling multiple PCR tubes

Polymerase chain reaction (PCR) is a method widely used in molecular biology to make many copies of a specific DNA segment. With Brady Corporation's new laboratory sample label, up to eight PCR tubes can be labelled simultaneously. Designed to resist a range of chemicals, and easily printable in any lab with a Brady label printer, the new B-492 PCR tube label is precise, reliable and efficient.

The B-492 PCR tube label contains eight smaller, perforated labels in a single label strip. The self- adhesive strip can be applied on 8 PCR tube labels in a rack and can easily be torn after application into separate PCR tube labels thanks to the perforations.

The B-492 PCR tube label is made out of polyester and will resist common lab chemicals, including DMSO, Xylene and Ethanol, as well as low and high temperatures.

Smart packaging

The pharmaceutical packaging of the future serves more purposes than merely protecting and marking medicines. Smart packaging builds a digital bridge between the manufacturer, distributor and patient because, due to digital technologies, packaging is able to communicate.

Schreiner MediPharm has combined its expertise in innovative specialty labels and integrated solutions with folding box manufacturer Edelmann. The result is smart medicine packaging with original digital features. It includes the BitSecure copy detection technology and a tamper-proof closure seal.

BitSecure is a printed, digital security feature. It is based on a high-resolution, random pattern whose delicate details are not discernible by the naked eye. In an attempt to copy the small random pattern with a size of just a few millimetres, the printed image will suffer a loss in precision and optical details. The pattern can be authenticated quickly and flexibly on-site using a smartphone or handheld reader and analysed via related software. Due to its small size, it can be easily integrated into existing packaging or label designs.

The closure seal with a void effect and an integrated NFC chip combines analog and digital technologies to deliver double tamper evidence: before the seal’s initial opening, the user reads the NFC chip using a smartphone and related app to receive confirmation of the product’s authenticity. If the seal is peeled off, an irreversible void effect will appear. If the user opens the packaging without previously peeling off the seal, the seal will break along the perforation. If the NFC chip is read again, a warning on the smartphone will indicate that the packaging has been previously opened. This makes any tampering attempt clearly visible. Additionally, interactive applications for patient information and assistance may be integrated into the NFC chip.

Bearing developments

Low-temperature reactions are widely used in pharmaceutical manufacturing. Temperatures of approximately -80 C are sufficiently cold to meet most requirements of cGMP (the Current Good Manufacturing Practice regulations enforced by the FDA), but these create design challenges for machinery components.
Only certain types of bearing material are suitable for use at low temperatures and high speeds. Additionally, the extremely harsh solvents and chemicals make corrosion a real threat.

Severely low temperatures can dramatically increase the viscosity of lubrication, a vital consideration for those using bearings in these environments. Increased viscosity can make the bearing difficult to rotate, rendering it ineffective.

According to Chris Johnson, managing director of miniature bearing supplier SMB Bearings, ceramics, in addition to being immune from corrosion, are non-porous and practically frictionless. Unlike stainless steel bearings, full ceramic bearings do not suffer heat build-up within the bearing and therefore do not need lubrication to help dissipate the heat. This means full ceramic bearings do not require lubrication to run - which overcomes the issue of high lubrication viscosity at low temperatures.

Full ceramic bearings are the only bearing class recommended to run dry at anything faster than very low speeds. Unlubricated full ceramic bearings do not run the risk of contaminating the product due to lubricant leakage.

Sterility testing

Cherwell Laboratories, a specialist supplier of products for environmental monitoring and process validation, has published an eBook titled, “Failure is not an option: Why sterility testing is so important”, which is available to download from Cherwell’s website.

The guide offers a full overview of sterility testing including why the sterility test is such an important requirement for the manufacture of sterile products. It provides some practical steps that will help ensure the standards as set out by the European Pharmacopoeia and GMP are met. The eBook also addresses the role of environmental monitoring programs and how these are critical to successful sterility testing, product quality and business reputation.

Topics covered include: the sterility test principle; what the expectations are within the pharmacopoeia and GMP; key considerations in the sterility testing process; how to tackle a sterility test failure and practical steps to minimise risk of contamination.