Designing drug devices

Extensive project management expertise and logistical control knowhow are required when working on a combination product from concept to launch. The biopharmaceutical company must select a suitable primary container, filling supplier, regulatory consultants, human factors engineering [HFE] experts and final assembly integrators. Of all the choices that need to be made, selecting the right drug delivery device partner should be considered one of the highest priorities.

An example of a disposable auto-injector with final labelling, pack and usage instructions

An increasing number of biopharmaceutical companies are looking at combination products, and there are many considerations in selecting device development partners. SHL argues that keeping it under one roof pays dividends.

Extensive project management expertise and logistical control knowhow are required when working on a combination product from the concept stage to eventual launch. Cross-functional teams from both the biopharmaceutical company and drug delivery device supplier must work together for several years to co-ordinate efforts in a collaborative manner, overcome related challenges and ensure the right steps are taken.

Taking into account the number of biologics coming to market and the entry of biosimilars, an increasing number of biopharmaceutical companies are finding themselves in need of the same services currently provided across various geographic areas by a broad number of suppliers and specialists.

Over the years, a few early-mover biopharmaceutical companies gained valuable experience producing their own devices, working with the suppliers of devices and by establishing a good rapport with companies providing related services. These early-movers have experienced first hand the extensive number of pieces within the combination product puzzle that need to be put together to move forward with a device such as an auto-injector.

Some of the choices that need to be made by the biopharmaceutical company include selecting a suitable primary container, filling supplier, regulatory consultants, human factors engineering [HFE] experts, final assembly integrators, and so on – all vital to the successful launch of the device. And the benefits of bringing an innovative device to market clearly make the investments of time, finance and resources worthwhile for biopharmaceutical companies.

Of all the choices that need to be made, selecting the right drug delivery device partner should be considered one of the highest priorities. And to support that selection process, visiting potential drug delivery device suppliers, looking at their track record and understanding their company culture are obvious steps, but it may also be helpful to focus on a number of other areas.

Involving another party may certainly add a new flavour to the uniqueness of the product, but doing so it may also slow down the overall development

Taking a product, such as an auto-injector, from early design and moving it towards being ready for mass production is a complex process. Development involves several stages such as planning, design, engineering and process validation. As a project moves forward, having both the design and development teams in the same company is ideal but not always possible. For example, the mechanical or technical design of the device may come from the device company, but the biopharmaceutical partner may choose to utilise an external industrial design company for the appearance of the device.

Involving another party may certainly add a new flavour to the uniqueness of the product, but doing so it may also slow down the overall development of the device by simply adding to the growing number of voices involved in the project.

Delicate balance

During the development process a delicate balance exists between providing device design features that fulfill end-user needs and making certain that device design is feasible to manufacture. It is between these two areas that one has to find equilibrium; if they come into conflict with each other, the end-user needs related to the device should always have priority over the manufacturing process, so long as the needs do not affect the safety and effectiveness of the device. Finding a balance is the key. SHL, for example, works closely with customers to develop devices that complement the manufacturing process.

During the development stage SHL ‘cuts steel’ and start to verify the design of the device by performing extensive physical tests, such as proving the mechanical sequence of the prototype devices. Numerous stereolithography models and other prototypes of device variations are reviewed for the industrial design and work is carried out with patient groups to find a shape for the device that patients like, but also a shape that can be produced and assembled efficiently. Over the course of the development process, the developer ensures that the design of the device is robust and that the functionality is there.

it is important to recognise that not all things can or should be brought in-house

Several factors involved in the development process rely heavily on consistent and effective communication among all parties involved in the project. This is one of the reasons why SHL has chosen to pursue the strategy of maintaining all key capabilities, processes and services needed to develop and produce drug delivery devices in-house. By doing so, it can enhance speed to market and help drive projects forward, especially during the development of any device.

However, it is important to recognise that not all things can or should be brought in-house. At times there is a need to involve experts or consultants for guidance in areas such as Human Factors Engineering (HTE), packaging materials, freedom to operate (FTO) opinions, etc.

In-house capabilities

Manufacturing advanced drug delivery devices requires an extensive range of capabilities. Tooling, moulding, automation, assembly and metrology are just a few of the many capabilities that are used. While maintaining such capabilities in-house is ideal, in some cases it is just not practical due to the extensive capital investment that a drug delivery device supplier is required to make.

Comprehensive in-house capabilities provide greater control over manufacturing processes, increasing speed and productivity

In addition to purchasing and maintaining the required machinery, developing the expertise needed to run this equipment at an optimum level is challenging and takes time. For these reasons, some drug delivery device companies, such as SHL, have followed a staged approach to incorporate key manufacturing capabilities ‘in-house’ over several years and many suppliers have been forced to accelerate this expansion in recent years due to an increase in orders and a desire to maintain a sufficient level of capacity.

Tooling and automation are two areas that deserve special attention by biopharmaceutical companies as these capabilities are sometimes outsourced by drug delivery device suppliers. Tooling is a significant expense in any drug delivery device programme and lead times must be planned for carefully. For high volume projects multiple sets of tooling are needed for production, safety stock and risk mitigation.

The intellectual property of new devices must be protected by strictly controlling who has access to these tools and related drawings. Taking tooling in-house is very costly for device suppliers, but can really help control quality and timeline concerns.

In addition, having a capability such as automation internally means that a device company can quickly build robust and flexible solutions for assembling and testing devices even while the design for the device is still being finalised. Certain tasks can be done in parallel and this will increase response times.

Metrology is another area that is vital to having a successful device project. For example, the dimensional precision of components is critical to ensuring a device can be properly assembled and that it functions as intended. Some devices have as few as three components, while others have more than 45.

Metrology study for drug delivery devices is a specialised skill and related training is paramount as it takes years to develop a certain expertise in this field. For high volume projects where greater metrology utilisation is needed, biopharmaceutical companies should ensure that their suppliers have enough of the right equipment, adequate numbers of well-trained staff and the resources to avoid potential bottlenecks in this area.

Spring production may be one of the last capabilities that people would think of ever in-sourcing, but in many ways the spring is the primary driver to successful injections performed by most auto-injectors. Some devices have three springs, each with its own unique requirements and some very specialised.

If springs are too powerful they can cause breakage; if not powerful enough injections can stall. Certain springs are ideal for dealing with highly viscous biologics, others are more suited to ensuring that a more consistent force is achieved and that completeness of injection is not an issue because no one focused enough attention on this component. In addition to springs, there are several other metal components crucial to the functionality of a high-end drug delivery device. All of these metal parts should be produced in-house to maintain optimum control and quality.

Final assembly

Once the sub-assemblies of a device are produced, the next step is integrating them with the biologic-filled primary container to create a completed combination product. Biopharmaceutical companies basically have three options to consider at this stage: carry out final assembly themselves; outsource to a third-party; or find a drug delivery device partner that can provide this service.

Additional assembly, labelling and packaging services improve end-product quality and speed-to-market

In response to customer requests to provide final assembly of combination products, drug delivery device suppliers such as SHL now offer final assembly, labelling and packaging services for devices to pharmaceutical and biotechnology companies. In the case of SHL, a specialised company was established as SHL Pharma, streamlining the production and distribution process for SHL Medical products, improving end-product quality and speed-to-market for customers.

By integrating an additional piece of the supply chain, SHL can now offer a full one-stop-shop, from product design to distribution. The advantage of in-house automation expertise to produce customised assembly and test equipment helped the company when setting up SHL Pharma operations in Florida, US.

From a quality and regulatory point-of-view, final assembly facilities should be ISO 13485 certified and registered with the FDA as a drug establishment, qualified to handle and distribute pharmaceutical products. Additionally, they should conform to all other regulatory requirements for medical device and pharmaceutical packaging and distribution, as per 21 CFR Parts 820, 210 and 211. The staff involved at this level will have both drug and device expertise to help ensure the safe production of the combination product.

In addition, when a project enters the final assembly stage there are a number of new considerations that must also be addressed – such as types of packaging, labelling, instructions for use (IFUs), inserts and more. Protective packaging not only holds the device for shipping, it also helps to protect it if designed properly. Clear IFUs will also help to ensure that end-users know how to use the combination product properly. Drug delivery device suppliers should – independently or in co-operation with external experts – be relied upon for guidance in these areas.

Inspiring integration

Enhancing the convenience and ease of administering biologics is a proven strategy for biopharmaceutical companies to augment product differentiation and to compete in an increasingly competitive market. As patients become more familiar with various types of drug delivery devices, they will expect suppliers of these devices to continue to innovate and to take their true user needs into consideration. Biopharmaceutical companies that proactively partner with experienced drug delivery device suppliers will be able to ensure that such needs are met and that projects can be completed on time.

Enhancing the convenience and ease of administering biologics is a proven strategy for biopharma companies to to compete in an increasingly competitive market

The term ‘inspiring integration’ is used internally at SHL to remind staff of the importance of continually improving, and strengthening the in-house capabilities and services that we can provide to our biopharmaceutical partners. Controlling the number of companies, suppliers and individuals involved in the design, development, production and final assembly of a combination product will result in improved communication, enhanced time to market and stronger control of the supply chain.

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