Outsourcing for IVD Manufacturers

Transcription

1 IVD TECHNOLOGY FOR IN VITRO DIAGNOSTICS DEVELOPMENT & MANUFACTURING JANUARY/FEBRUARY 2010 VOLUME 16 NO. 1 IVDTECHNOLOGY.COM Outsourcing for IVD Manufacturers Applying the product definition process in developing IVDs Instrumentation Development In Person: Integration and consolidation in IVD instruments A CANON COMMUNICATIONS LLC Publication PLUS: The industry effort to fight the tax on IVDs ON THE WEB ivdtechnology.com

2 OUTSOURCING FOR IVD MANUFACTURERS Manufacturing obstacles in IVD product development IVD manufacturers are looking to contract partners to provide guidance and relevant experience to overcome design and manufacturing challenges. BY WALTER GILDE AND DONNA HOCHBERG With the IVD market changing rapidly, the pressure to deliver new products to market less expensively and more efficiently is mounting. To reduce costs and shorten product development cycles, some OEMs and startup companies have been turning to contract instrument developers and manufacturers for their guidance and relevant experience to overcome common development challenges. As partners to major OEMs and start-ups, contract manufacturers can offer insights on the technical trends affecting the IVD sector and help develop solutions to meet the industry s changing needs. The changes in the IVD industry are being driven by increased laboratory test volumes and growing pressure to lower test turnaround times (TAT) with fewer skilled lab technicians. Any new product launches must be able to address this demanding environment. Such sweeping demands in the industry are accelerating the development of three specific areas of advancement: pointof-care (POC) technologies, automation, and graphical user interfaces. This article will examine these trends, outline common obstacles associated with them, and discuss how working with contract partners can overcome product development challenges by showing examples of instruments that Percent of Professional Testing Revenues $3.6 billion Other Coagulation Hematology Clinical Chemistry Rapid ID Blood Gas Glucose Figure 1. The 2008 U.S. professional POC market (excluding patient self-testing) was valued at roughly $3.6 billion worldwide, and its estimated annual growth is 7-10%. were introduced to the market with the help of a contract partner. Rise in POC Technologies Performing IVD tests at or near the location where patients receive care facilitates the medical decisionmaking process by eliminating delays caused when sending samples to laboratories. Faster test results may improve patient care in urgent situations, such as intensive care units or emergency rooms. POC technologies may also improve patient treatments and allow healthcare professionals to manage their patient s care while they are with them, without having to wait for lab results and meet with them later. These factors have been contributing to an annual growth rate of 7-10% in the U.S. professional POC market (not including patient selftesting), which currently accounts for about $3.6 billion of the overall IVD sector (see Figure 1). The desire for faster test results is undeniable. However, in order for an IVD product to be a viable POC technology in the marketplace, it must meet a different set of definitive requirements than a laboratory IVD device. Most importantly, POC instruments must be simple to use since the end users are usually not trained lab technicians. Specific POC device features should include minimal maintenance requirements and onboard calibrations to ensure accurate test results, a user-friendly software interface, integration with laboratory and hospital information systems, and easy-to-use disposables that contain all the reagents for sample processing and testing. POC instrumentation should also have a small footprint and in some cases be portable since both hospital clinics and physician offices have limited space. While such requirements may seem simple, they present IVD companies with a variety of design and manufacturing challenges. Most notably, a number of POC technologies require more complex disposable cartridges containing multiple reagents to process only one patient sample at a time, compared with simpler

3 disposables in higher volume laboratory instruments. With this added complexity, product development teams must work together to ensure a smooth integration of the disposable cartridges with the instrument design and minimize costly redesigns. Working with a contract manufacturing partner that has experience in integrating disposable cartridge technologies with instrument design is one option to consider during the product development process. Avoiding Too Much, Too Soon Many OEMs and start-up IVD companies fall into the too much, too soon trap when developing their POC technologies. Such companies do not demonstrate the feasibility of the disposables, reagents, and assay processes prior to beginning to develop the hardware and software for the instrument with their contract partners. Even subtle changes in the disposable design can require major changes in the instrument s architecture, leading to increased development costs and schedule delays for design overhauls. However, IVD companies can take certain steps to avoid such costly delays. Initially, the ability to meet assay performance requirements should be demonstrated at the macro level before scaling down to the micro level. In addition, cartridge development should be divided into smaller functions, followed by designing and testing those functions before combining them into an integrated disposable. This approach better defines the variables, how to control them, and how they are interrelated. Furthermore, a systems approach is needed when designing POC technologies. Because disposable design and instrument design go hand-inhand, having a contract manufacturing partner involved in the product development process can be helpful. Flexibility is enhanced when the disposable and instrument are developed together because tradeoffs can be Figure 2. The LabNow instrument is designed to perform cellular and molecular assays and will be used in medical applications such as tests for CD4, hemoglobin, liver functions, and a wide range of infectious diseases. weighed and the best cost-benefit decisions can be made. By working with a contract instrument designer and openly communicating any design changes in either the instrument or disposable, an IVD company can avoid schedule delays and redesigns. Closely Considering Materials and Environment Often when designing POC technologies, IVD companies fail to consider material compatibility requirements, the differences between prototype and production methods, and distribution logistics. All these factors affect the production and distribution of POC instruments. However, companies can address them by working with a contract instrument designer that has experience in such areas. IVD companies must take into account material considerations early in the product development process. Failure to account for material differences can delay a transition from design to full-scale manufacturing. For example, compatibility of materials with sterilization methods can affect product performance. Silicon can lose elasticity after undergoing gamma sterilization; therefore, a syringe design that includes a silicon O-ring might leak after being exposed to the gamma sterilization process. IVD companies must also consider the use of materials in hand-built prototypes versus mass production methods when designing and manufacturing POC instruments. Often in rapid prototyping, various resins are used that are similar to but not exactly the same as molded parts. Prototype machined parts may act differently than molded production parts that have required drafts and wall thickness constraints. To deal with such materials issues, companies should ensure that the design team has resources with manufacturing engineering and materials science expertise. Finally, taking into account the logistics and environmental storage requirements of disposables and consumables upfront is important to ensuring a successful product for end users. IVD companies with little experience in designing POC technologies often fail to consider how disposables will need to be shipped, stored, and disposed. Storage and hazardous disposal options in a POC device user s setting may be more limited than those in a larger laboratory. An example that encompasses Figure 3. The LabNow instrument processes the blood sample, analyzes it using fluorescent measurement, reports results, and disposes of the waste products in less than 15 minutes, making it ideal for use in a physician s office or hospital setting.

4 many of the above challenges is a POC technology platform by Lab- Now Inc. (Austin, TX). The instrument is designed to perform cellular and molecular assays, and will be used in medical applications such as tests for CD4, hemoglobin, liver functions, and a range of infectious diseases (see Figure 2). A virtual lab on wheels, the product processes a blood sample, analyzes it using fluorescent measurement, reports test results, and disposes the waste products in less than 15 minutes, making it ideal for use in a physician office or hospital Number of Certified Lab Technician Graduates Year setting (see Figure 3). Essentially, a medical professional collects a blood sample through a fingerprick and places it into a port on the disposable BioChip, which is then inserted into the instrument. The test result is quickly presented without any further intervention. The major design challenge encountered by the LabNow technology was due to the aforementioned too much, too soon trap. The disposable BioChip and chemistry inside it were initially developed independently of the full system design, without enough consideration of the mechanical and optical interfaces needed to ensure the entire instrument would perform properly. The contract partner was brought in late during the product development process, and as a result, the instrument s time to market was delayed, and the development costs increased due to redesigns of the BioChip. Instead of continuing to compartmentalize the various phases of product development, LabNow is now working with KMC Systems Inc. (Merrimack, NH) to integrate the entire process and deliver the product to market in a timely manner. Implementing a systems approach and openly communicating among all design and manufacturing teams have Tech. Graduates Lab Test Volumes 2006 Figure 4. Overall lab test volume rose 15% from 2000 to 2006 while the number of certified laboratory technician graduates decreased by 50% in the same time frame. 10 Overall Lab Test Volumes (billions) helped LabNow overcome the initial development challenges. Increasing Demand for Automation The demand for automation in clinical laboratory testing has been continually increasing due to the heightened work strain on labs. From 2000 to 2006, overall lab test volumes rose 15%, while the number of certified laboratory technicians fell by 50% (see Figure 4). There are also significant opportunities for greater automation in many laboratory testing areas, including molecular diagnostics, flow cytometry, and microbiology. Similar to POC technologies, lab automation can provide more-rapid TAT and overall improvements in patient care by providing accurate and consistent test results. Even though a high degree of user interaction in the lab is still required, reduced labor and more-efficient testing protocols resulting from automation can also help laboratories manage their costs. The design challenges presented by instruments that automate laboratory processes can typically emerge when there is a communication breakdown between an IVD company and a contract design partner. Unlike humans, machines cannot easily adapt to different sizes or volumes that affect completing a test process. For example, while a laboratory technician would not give any thought to grasping a 12-mm diameter tube as opposed to a 20-mm one, a machine that automates the process must be designed to identify and accommodate such differences. Navigating the relationship with a contract design partner to develop lab automation can be complicated, but several methods can help streamline communication and ensure a successful product launch. Defining Terms and Requirements As simple as it may seem, the first step to establishing good communication with a contract manufacturing partner is to create a glossary of common terms. A mix-up over even the most common words (e.g., tube and vial) can lead to increased development costs and delays if it is discovered too late. Nearly all IVD companies have developed their own jargon that can be confusing to outsiders. Putting together a glossary at the start of a project and including it in the product requirements document (PRD) will help both parties avoid embarrassing mix-ups and costly delays in the product development program. Second, when defining product requirements, deciding which functions and features are non-negotiable is critical since any potential tradeoffs may need to be identified to meet cost and size restrictions. Working

5 OUTSOURCING FOR IVD MANUFACTURERS with contract partners to identify upfront what functions can and cannot be eliminated will save significant time later in the product development process. In addition, IVD companies should identify the areas in which a small change (e.g., adding a feature to a part) might ease the automation development effort and result in financial savings and reduced complexity (see Figure 5). An example of the importance of defining requirements comes from an OEM that developed an automated processor for preparing bacterial samples for identification and drug testing. The product was challenging from the outset due to the short timeframe to introduce it to the market, which made it even more critical for the OEM and contract partner to define clearly the requirements. The OEM implemented a rigorous internal process to develop a single-level PRD that articulated a timeframe and what needed to be achieved. Furthermore, the contract partner assembled a cross-functional team to review appropriately the requirements. After defining the requirements, the team had to identify the areas where features could be taken out so that the product would have an appropriate price point for end users. One strategy for determining trade offs in features was to develop an early prototype unit for use in focus group testing, which was completed five months after beginning the project. The end-user interviews found that automating the inoculation of the sample-to-test cartridge was not worth the time and cost for development or the additional product costs. By clearly defining the product requirements up front and confirming them through focus groups, the OEM and contract partner were able to bring the product successfully to market within the rigid timeframe and price range. Evaluating Chemical Handling and the User Environment Practically all chemicals and biological substances have specific handling requirements and tolerances (e.g., temperature, shelf life, and humidity). Furthermore, they can be hazardous to humans and detrimental to certain materials. Such substances must be carefully evaluated and incorporated into lab-automated processes, which makes it critical to share such information with a contract design partner. An IVD manufacturer can develop a material safety data sheet that provides a detailed description of each substance used in the process and its handling requirements. Figure 5. Identifying areas where a small change might ease the automation effort can result in financial savings and reduced complexity. Another often overlooked factor is implementation discovery, or how, where, and by whom an instrument will be used. Manufacturers must take into account power source, size, and frequency of use in the design of an automated system. Considering such factors up front can save valuable product development time. For example, it is naïve to consider pneumatic actuators if the laboratory where they will be used does not have a compressed air source. Because the environment where a device will be used is critical to everything from basic material selection to size, communicating such information with the contract design partner is important to keeping the project on track. Increasing Focus on Graphical User Interfaces As noted earlier, the number of specially trained laboratory technicians is declining, which means that diagnostic technologies are being operated by lesser trained lab personnel. IVD companies must develop instruments that feature easy-to-use software incorporating the principles of human factors engineering. To ensure that IVD instruments provide accurate test results regardless of the operator, the use of graphical user interfaces (GUIs) is increasing, and more complex software design is being required when developing diagnostic technologies. Such software dictates a thorough understanding of how a user interacts with an instrument, which must be implemented in the interface design. Such complicated software solutions present a number of design challenges for OEMs and start-up companies, which makes it imperative to define software requirements. Accounting for Human Factors in Software Design Taking into account the principles of human factors engineering is a vital first step in designing a successful GUI. Previously, when instruments were operated by highly trained laboratory personnel, IVD manufacturers could design GUI to provide a user with multiple complex options on single screens, which made the software interface simpler but allowed skilled technicians greater autonomy. However, manufacturers must now design GUIs for lesser trained personnel, using software wizards to guide users through distinct steps with little room for user error. To complicate further the software design, many instruments must also incorporate an expert mode for cases when they are being used by skilled technicians. Incorporating multiple modes in a GUI also requires additional testing

6 to be worked into an instrument. When working with a contract manufacturing partner to navigate the design of such complex GUIs, developing a detailed software requirements specification document is a must. This document should define a myriad of items, including a typical user profile, the lab workflow, and the chain of custody for a sample. For example, the software design team must know if a touch screen is necessary, and if so, whether or not users will be wearing gloves when using the touch screen interface. Such requirements introduce a higher level of design constraints for a GUI, such as larger, easy-to-touch buttons. Understanding such requirements up front will ensure a GUI is designed with human factors in mind. Conducting usability studies and voice of the customer surveys can also ensure that a GUI is functional and easy to use. A key element to interface design is focusing on the tasks that are most often used. Soliciting feedback from users is the best way to determine which features are most important. Such studies can also help the contract partner understand the laboratory s work flow, which can affect the software design. For example, a user may identify a particular function (e.g., sample preparation) that needs to be performed while the IVD instrument is processing a different sample. Recently, while designing a sample preparation instrument for liquid-based cytology, a customer identified a need for increased throughput. To accomplish this requirement, a GUI had to be adapted to accept information for the next batch of samples while simultaneously processing the current batch. Ultimately, the update to the GUI allowed the user to enhance efficiency. Conclusion Successful contract design and manufacturing requires clear and frequent communications between the partners in every industry. However, the IVD industry is unforgiving of any lapses in coordination, because disposables and instruments have to work together seamlessly, the ultimate designs integrate numerous different technologies ranging from mechanical engineering to chemistry to microfluidics to optics to electronics and software, and complex tests are performed at rapid speeds by operators with very little lab expertise. 5 Walter Gilde is business development manager at KMC Systems Inc. (Merrimack, NH), an Elbit Systems of America company. He can be reached at walter.gilde@ elbitsystems-us.com. Donna Hochberg, PhD, is a manager at Health Advances LLC (Weston, MA). She can be reached at dhochberg@healthadvances.com.