Plastics in Drug Delivery Devices: Roundup

White Paper Explains Effects of Static Electricity on Plastics Used in Drug Delivery Devices

Dr Joe Bell, product development engineer at US-headquartered compounder RTP Company, has written a white paper which details the effects of static on plastics used in drug delivery devices. The paper is co-authored by Josh Blackmore, RTP’s global market manager for healthcare.

The abstract of the paper is: “Drug delivery in dry powder and aerosol inhalers can be hindered by static attraction of the drug substance to plastics used in the drug flow path. RTP Company has initiated a series of projects [experiments] to characterise this interaction, measure the effect of static build up, and create conductive plastic solutions which reduce the static charge in plastics used in the drug flow path of drug delivery devices.”

The paper is divided into the following sections: objectives, introduction, static electricity, conductive standards, specifications, tests and technologies, experimental setup, results, conclusions, selection criteria for plastics suppliers, and references.

In essence, the experiment described in the white paper tested the effect of static on two plastic tubes—one with and one without an antistatic polymer compound—while controlled static charges were placed on the tubes. The static effect was measured by adding a predetermined weight of lactose powder to the tubes and weighing the tubes before and after the powder was added to see how much powder sticks to the plastic.

The conclusions of the experiment are as follows. Static charges that build up on the plastics used in the drug flow path and housing materials in pressurised metered dose inhalers (PMDIs) and dry powder inhalers (DPIs) have demonstrated the ability to attract the drug formulation and therefore reduce the amount of drug delivered.

Antistatic plastics help to eliminate this variable in both PMDI and DPI devices. The paper cites RTP’s PermaStat brand of antistatic compounds as an example. The PermaStat compounds reduced the drug from sticking to the plastic compounds in this test from 20% down to 2.5%. This is an 87.5% improvement in drug delivery. In addition, the PermaStat compounds reduced the variability in the amount of drug delivered.

RPC Develops “Twist n’Hale” Dosing Wheel and Dosage Count Indicator for Powder Inhalers

The group responsible for drug delivery devices at German packaging manufacturer RPC Bramlage-Wiko has announced it has developed two features available for inhalers—Twist n’hale [read twist and inhale] and a dose count indicator for pressurised metered dose inhalers (PMDIs).

RPC Formatec’s Twist n’hale is a new contraption which allows users to twist a wheel on their inhaler to prepare it prior to breathing in the dose. The system, created for blister-based powders, is said to offer a simple-to-use operation across a wide range of different flow rates.

The Twist’n’hale features a turning wheel on the side of the container. When the cap is opened, the wheel is rotated clockwise in a single movement up to the stop point, which releases the dose. Users then inhale and close the cap. Usage is monitored via a dose counter and reloading the dispenser is easy.

RPC Formatec’s new Dose Indicator has a counter that indicates the number of times an inhaler has been used. The company says it enables users of all types of pressurised metered dose inhalers (PMDIs) to accurately and reliably monitor the number of doses taken from their inhalers.

The new patented device is FDA approved and has been designed to fit all common types of valves including 3M, Bespak, VARI and Valios. As well as being available for new inhalers, the Dose Indicator can be easily integrated into existing dosing aerosols with only slight modification of the mouthpiece.

Drug Delivery Device Functionality is Driving Demand for Engineering Polymers, says DuPont UK

Ian Wands, market development representative at DuPont’s UK subsidiary in Hertfordshire, England, has written an article in European medical device manufacturing magazine EMDT about engineering polymers for drug delivery devices. The article describes how a growing trend for design functionality in drug delivery devices is stimulating demand for specialist engineering polymers.

The article will help designers consider DuPont’s materials during their material selection process. It is split into the following sections—introduction, including the pyramid of thermoplastic materials sorted by melt temperature; semi-crystalline polymers; functional plastic components for devices, which talks about POM, unreinforced nylons, PBT polyesters and TPEs (including DuPont’s Hytel TPE-ET); specially tailored grades for the medical device market; low friction materials; and trends and future needs.

Two case studies are presented: a reusable insulin pen designed by Industrial Design Consultancy (IDC), based in the UK, and a disposable injector pen featuring a low friction grade of Delrin acetal homopolymer. For a copy of the report please contact the editor at sam.a@rapidnews.com.

Technoflex Focus on Parenteral Nutrition

In the April 2013 edition of Flexmag, the customer magazine of French manufacturer of IV bags Technoflex, Sylvie Ponlot, editor in chief, has focused on the subject of parenteral nutrition, feeding patients intravenously in the event of a deficiency of their gastrointestinal tract.

The magazine features two articles on the subject. In addition, an interview with a Technoflex line operator about switching manufacturing operations from PVC to PP—among other things—follows a piece on biopharma.

The first article about parenteral nutrition looks at the complete picture when manufacturing IV systems for parenteral nutrition, including dealing with  ingredients like glucose, lipids and amino acids and preventing oxidation to maintain freshness. The article asks whether it is best to use compounded or ready-to-use preparations.

The second parenteral nutrition article looks at PP multi-chamber bags, made from PP-based film with a high oxygen barrier. The different chambers allow ingredients to remain separate. Peelable welds are included to maintain the separation. For the clinician to mix the ingredients, the welds can be squeezed and broken.

The report about biotech describes a perceived race to develop biotech products in new emerging markets, especially Brazil, Russia, India, China and South Africa.

Schott Doubles Production Capacity for Cyclic Olefin Copolymer Syringes

To address the increasing global demand for prefillable polymer syringes, German glass specialist Schott has expanded its manufacturing capacity for small size Schott TopPac syringes. Small size syringes comprise volumes from 1 to 10 ml.

A new production line installed at Schott’s site in St Gallen, Switzerland, has expanded the existing production capacity by 100% from April onwards. This enables the company to offer customers a greater degree of flexibility and ensure supply security.

Schott describes itself as a pioneer in ready-to-fill syringes made of cyclic olefin copolymer (COC). Over the past 15 years, Schott made significant investments to develop and industrialise COC material for pharmaceutical containers for injectable drugs. Schott’s brand of COC syringes is TopPac.

COC is an inert material and the Schott TopPac syringe system is designed to be compatible with a broad range of drugs. COC has excellent barrier properties and, as a result, Schott’s TopPac syringe system allows long term storage of drugs even in small syringe sizes.

In addition, Schott TopPac syringes have a glass-like transparency, and are break resistant and lightweight. Schott TopPac syringes are available in capacities ranging from 1 ml to 50 ml, with cross-linked silicone for optimal functionality.

Schott says that pharmaceutical companies benefit from the fact that TopPac syringes are manufactured in cleanrooms with a fully automated process starting from injection-moulding to the final packaging in nest and tub. The syringes are sterilised and are ready for aseptic filling operations.

Schott says “it intends to achieve further growth in the field of polymer and glass syringes and also underscores its commitment to offer ideal product solutions to pharmaceutical companies—today and tomorrow”.

Makrolon Polycarbonate Selected for Valve Connectors to Prevent Exposure of Cytotoxic Drugs to Medical Workers

The US subsidiary of German polycarbonate manufacturer Bayer MaterialScience has announced that its Makrolon brand of polycarbonate has been used to make valve connectors in Infusion Innovations’s (I3) Q-FLO cytotoxic drug delivery device. Bayer says Makrolon has been selected for its strength, clarity, lipid and chemical resistance, biocompatibility and gamma stability.

Q-FLO is cleared by the FDA for use in reconstituting, dispensing or transferring, administering, and disposing of potentially hazardous fluids. These fluids include those used in chemotherapy, radioactive isotopes, blood products and nuclear medicine, as well as non-hazardous fluids. The connector can be embedded into the barrel of a 3 ml (3 cc) syringe.

The medical grade polycarbonate meets IS0 10993-1 and USP Class VI tests for up to 30-day contact with human tissue.

The use of Makrolon is important as it represents a significant advance in the manufacturing of closed system devices, offering improved safety and convenience for healthcare workers administering cytotoxic drugs to patients.

“When engineering the Q-FLO we wanted an approved and established material that had FDA clearance along with a proven safety and functional profile,” said Dr Babak Nemati, president and CEO of I3. “Bayer’s plastic not only met these stringent requirements, it also offered the level of chemical resistance required for use with cytotoxic and nuclear medicine.”

According to I3, the Q-FLO closed, no drip, valved male luer connectors offer complete swabability at the top of the connector, with a flat, smooth surface allowing for true friction disinfection during pre-access swabbing; and a sequential locking mechanism, which prohibits accidental discharge. Additionally, it has a unique visual indicator confirming connection status.

“The Q-FLO represents an innovative product that meets a real need in the healthcare market,” said Bruce Fine, market segment leader for the medical and consumer products, polycarbonates group at Bayer MaterialScience’s US subsidiary. “We worked closely with I3 to provide a high-quality, proven material that meets rigorous requirements and reduces the risks for medical professionals administering life-saving medications.”

Gerresheimer Builds New Czech Production Hall to Fulfil Sanofi Injector Pen Commitment

German drug delivery device and components contract manufacturer Gerresheimer has built a new production hall in the Czech Republic to produce components for a new order of insulin pens from healthcare company Sanofi. The preparations for the production lines and all required qualifications and validations were completed within eighteen months.

The structural components for the disposable insulin pen manufactured in the new hall consist of several plastic parts manufactured by Gerresheimer Medical Plastic Systems. The final pen assembly is carried out at Sanofi’s facility in Frankfurt in Germany. The production and assembly of the structural components involves injection moulding machines, removal robots, different measuring and testing systems as well as pad printing lines.

The complex and highly automated assembly line with several assembly and testing stations was planned and installed entirely by Gerresheimer Medical Plastic Systems. The specialist also developed several of the required moulds. These were manufactured by their in-house mould engineering department. Especially for this project, the manufacturer built a new hall with 3,500 sqm cleanroom areas to ISO class 8 for production and assembly as well as a fully automatic high-rack storage facility.

Carsten Dormeier, project manager at Gerresheimer’s technical competence centre in Wackersdorf, Germany, pointed out that adherence to the extremely tight schedule is the most impressive achievement of the project: “We were able to adhere to the ambitious schedule of this extensive project from the start of the planning phase in Wackersdorf through to production startup in Horšovský Týn [location in the Czech Republic] thanks to the high commitment of our staff at both facilities.”

The high speed of development will be maintained. The new project is the second Sanofi order for the production of insulin pens from Gerresheimer. Reusable pens are already manufactured at the company’s Pfreimd facility.

Becoming a Full Service Solution Provider: IGS GeboJagema Observe Changing Nature of Traditional Toolmaker

Dutch medical mouldmaker IGS GeboJagema has written about how working with manufacturers of drug delivery devices requires far more than simply making a tool for one or two parts. IGS cite the example of a modern drug delivery device comprising as many as 20 moulded parts with drug formulation timeframes being 10-15 years in development and costing more than €1 mn.

The message that the report portrays is that tooling for drug delivery is a major project and requires a toolmaker that has a strong “financial backbone”. The full report is as follows.

Global modern pharmaceutical companies audit with their own sourcing teams high tech toolmakers and value their capabilities on project management—design for manufacturing and mould validation.

The development costs of a new drug can increase to more than €1 mn and can take 10 to 15 years development time. In most cases, new respiratory drug delivery devices need to be developed to achieve the optimum drug delivery to the human lung.  

In the last decade IGS GeboJagema experienced that the required part-for-manufacturing knowhow is not always available at the pharmaceutical companies and often external medical device development companies are involved in the engineering of this new drug delivery platform. A new COPD respiratory inhaler device normally consists of more than 20 injection moulded thermoplastic parts. This is where the need for a professional tooling partner for pilot-, pre production- and multi-cavity moulds is born.  

Toolmakers that supply the healthcare industry and are involved in large scale tooling programmes such as the delivery of multiple 32-cavity hot-runner moulds need to have more skills than just innovative mould engineering and accurate mould manufacturing capabilities. They have to add value with senior project management, design of experiments (DOE) and design failure mode and effects analysis (DFMEAs), captive validation capabilities for factory acceptance tests, skilled process engineers and appropriate metrology equipment. Besides these technical skills, toolmakers supplying the healthcare industry need to have a solid financial backbone to be able to support the moulds during the full lifetime of the medical device.

In the 1990s IGS GeboJagema recognised the need to change from an ordinary mouldmaker to a full service solution provider and invested in tool manufacturing efficiency programmes, such as robotised automated equipment for high speed milling and spark eroding, and enhanced the engineering team to almost 25 professionals, including five project managers.

Each project manager is dedicated to a medical device project. Some projects even have a back-up project manager, to safeguard the continuity of the project. So from start to finish the project manager is the contact person during the entire project for the customer, whether it is about mould design, Gantt charts, DFMEA studies or metal steel safe re-cuts.   

IGS GeboJagema also installed a new validation centre with more than 10 injection moulding machines in separate validation cells to guarantee the full secrecy of the customer’s developments. The factory acceptance test (FAT) of the moulds at IGS GeboJagema can be done either on IGS’s own machine or on a customer’s injection moulding machine which can be temporarily installed in one of the available validation cells.

IGS GeboJagema is equipped with hot-runner controllers, chillers, coolers, resin drying and masterbatch colouring equipment. The well-trained process engineers are more than operators, but are always striving to develop the most efficient and optimum processes. They exactly know how to run a factory acceptance test, including dry cycle tests, process development, first out of tool (FOT) programmes, balance of fill analyses, DOE analysis and 4-hour FAT runs and prepare a number of shots for a full first article inspection report. They will make sure that moulds are production-ready, within the demanded process performance index (Ppk) values and dimensional tolerance. This is why IGS GeboJagema is involved in medical devices programmes and is able to support large scale tooling projects. IGS GeboJagema has transformed from a normal average toolmaker to a full service solution provider and says it is the professional partner the modern pharmaceutical companies are looking for today.  

Maillefer Adds Features to PML Model for PVC IV Tubing Extrusion

Swiss manufacturer of extrusion machinery Maillefer has announced new features for its PML extrusion line model for the production of PVC intravenous (IV) tubing. Thanks to cooperation with the world’s leading medical device manufacturers, innovations on tube surface finish and conditioning have been brought about. Advantages are said to be an increased speed and optimised processing carried over to the manufacturing processes located downstream.

The press release announcing the new features includes the following.

A smooth and glossy IV tube surface may be appealing but it has the undesirable effect of surface tackiness, which is accentuated when conditioned on coils. The winding and later unwinding operations are slowed as a result. Maillefer has added features to its extrusion technology that result in a tube surface with lower adherence. The positive gain is felt on the extrusion line speeds and on the following operation being sourced with coiled tube.

Three conditioning possibilities are available from the line: a full length coil, a multiple length coil, and individual cut lengths. The classic method calls for tubes of long length wound into coils through use of a fully automatic dual coiler at the end of the extrusion line. The delivered coil then needs to be unwound and cut into individual lengths during the assembly step. Another solution is to deliver short lengths produced directly on the extrusion line with an integrated cutting machine. The third solution innovates by combining both methods. Here, short tubes are prepared online, while maintaining a tractable tube for coiling. The advantage is having easy-to-handle coils while delivering tube that is easily separable.

Maillefer’s PML 032 line is geared for a speed of 300 m/min. Manufacturers’ typical tube constructions are produced at 200 to 240 m/min. The line operates at constant speeds, even during coil transfers. Available control features include process monitoring, data logging, event alarms, recipe storage, scheduler, report generator and video monitoring. The entire line is designed and built to the strict requirements of the medical device industry.

In 2007 Maillefer announced that IV drug manufacturer B Braun’s US subsidiary ordered and installed a customised Maillefer PML extrusion line. The order for the machine was placed in 2005.

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