What A Successful CMO For Diagnostic Consumables Looks Like
Introduction
There is a clear trend in the diagnostics space toward higher complexity consumable products. Various components of a diagnostic assay are now integrated entirely on a single consumable, with its corresponding system analyzer often only responsible for simple mechanical actions. This increase in complexity drives more compact and efficient diagnostics systems, but it simultaneously raises new issues regarding manufacturing. The intricacy of emerging diagnostic consumables necessitates manufacturing competencies that span a wide range of disciplines, thereby raising the standards for a CMO to be successful in this space. As diagnostic companies continue to develop these complex consumables, the need for a strong relationship with a consumable diagnostics CMO specializing in everything from early product design to final product manufacturing will become increasingly more important.
A Successful Consumable Diagnostics CMO
Many firms can provide molding and basic manufacturing services. Only a few within this space, however, meet the standards of a true consumable diagnostics CMO, providing the technology integration necessary for manufacturing emerging consumable diagnostic products. Here, we explore what the technical competencies and operating segments of a CMO for diagnostics consumables looks like.
Technical Competencies and Integration
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Replication (Thermoplastic Injection Molding) |
Competency in injection molding is incredibly important when considering the high level of precision required by diagnostic products. For instance, the tolerance for manufacturing microfluidic products in the development stages is ±1 micron; more extreme deviations would introduce the risk of bubble formation in the intersection of microfluidic channels and render the test and product unusable. |
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Reagent Handling/Storage |
Many consumables now have integrated components for all the necessary reagents to carry out a particular assay – effectively eliminating the need for external reagent addition. A CMO must be able to store and handle these reagents during the manufacturing process, including both liquid and powder reagents for blister pouches or separated compartments. |
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Surface Modification |
Basic surface modification can include hydrophilic or hydrophobic coatings. Oftentimes, assays require more involved surface modifications, including antibody attachment. For instance, the surface modification necessary for a circulating tumor cell (CTC) assay requires that a polycarbonate surface go through UV light exposure and carboxylic acid treatment prior to the actual attachment of the antibodies. |
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Assembly Technology |
Diagnostic consumables are composed of many parts, thus requiring sophisticated assembly technology. This includes the assembly of component parts such as a consumable’s plastic cartridge and spring system, as well as the binding of various materials through bonding or welding processes. |
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Automation Design and Implementation |
Complementary to assembly technology, a CMO must have competency in automation processes. This not only includes knowing when to automate a process based on the volumes and consumable itself, but also how to implement an automation solution that is cost and time optimized. |
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Sensor Integration |
Biosensor technology through the use of components such as electrodes are increasing in the diagnostics space as a more compact alternative to traditional optical target detection methods. Electrode integration in point-of-care cartridges effectively creates a single consumable that can handle all the steps of sample collection, sample preparation, reagent addition, and target detection. |
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Supply Chain |
While a successful CMO does not need to manufacture all component parts in-house, it must be knowledgeable in the coordination and management of additional parts and activities to ensure a quality product for the customer. |
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Cleanroom/Sterile manufacturing |
Maintaining a clean and sterile environment is a crucial aspect of all medical device manufacturing. The contamination of drug delivery devices could have severe consequences in terms of patient immunogenic response, and contamination of diagnostic products compromises validity of the results. Of particular note are the ubiquitous RNase and DNase enzyme contaminants that are present in the environment and many biological materials. These enzymes degrade RNA and DNA, respectively, effectively threatening all molecular diagnostic assays that rely on the detection of fully intact RNA and DNA in samples; to counter this, there are many products available offering detection and elimination of the enzymes. It is important for a consumable diagnostics CMO, therefore, to have cleanroom and sterile manufacturing knowledge and capacities – protecting against any form of contamination such as RNase and DNase. |
Operations: End-to-End Integrated Service Solutions
A diagnostic consumables CMO is first and foremost well-versed in the diagnostics market. A thorough understanding of the current technologies, emerging trends, and market drivers is a crucial characteristic of an ideal consumable diagnostics CMO. The rationale behind this notion is best illustrated by analyzing the overall manufacturing chain:
Figure 1: Manufacturing process chain
The cost-saving potential for manufacturing diagnostic consumables is almost entirely in the back-end-processing. Processes such as sealing, assembly, reagent storage, and surface modifications all have a wide spectrum of potential costs; in other words, two cartridges performing the same assay could vary in cost of production due to processing discrepancies. The best practice for both diagnostics companies and CMOs, therefore, is to collaborate at the design and development stage and evaluate how design for manufacture and assembly (DFMA) practices can best be applied moving down the chain.
Early collaboration at the design stage not only provides cost-savings at the processing stage, but it also provides a CMO the opportunity to assess the potential for added-value to a design. In this way, a diagnostic consumables CMO is truly an integral part at every stage of the manufacturing process chain – from design consultation to quality product manufacturing. This relationship and comprehensive service solution, of course, would not be possible without the CMO’s thorough knowledge of the diagnostics market, including its emerging trends and current technologies.
Consumable Project Case Study
In a recent project, Phillips-Medisize had the opportunity to manufacture a complex consumable in collaboration with a biopharmaceutical company. This consumable included dry reagent pellets and microfluidic components; the integration of dry reagents called for assembly in a dry chamber space and the microfluidic components required tight tolerances for the device to meet functional requirements.
From the technical competency and technology integration perspective, Phillips-Medisize was well positioned to efficiently and effectively develop this complex consumable. New air handler systems were installed to accommodate for the dry chamber space requirement, and Phillips-Medisize injection molding competencies with tight tolerances had been well established. In this case, however, the biopharmaceutical company had a relatively established prototype design for their consumable prior to Phillips-Medisize’s involvement. Consequently, despite an overall collaborative dynamic, there was limited flexibility in terms of implementing design suggestions and certain geometric changes that could improve the overall quality and structure of the final manufactured product. In the end, very few improvement suggestions could be practically implemented into the final product, causing a slightly longer lead-time for the evaluation prior to establishing production-manufacturing processes.
Product Development Cycle
The Phillips-Medisize Development Cycle (Figure 2) articulates the benefits to working with a CMO that has experience and expertise designing, testing, and manufacturing complex medical devices. Often easier said than done, establishing involvement prior to the prototype design provides flexibility for design improvements and process requirements. Early involvement of a CMO provides the greatest benefit long-term. The results are the benefit of designers, testers, and manufactures working to solve the articulated user needs without any arbitrarily established design constraints.
Maintaining knowledge of the medical device landscape and requirements provides a library of learnings and technical experts that are able to navigate medical device requirements decisively. These learnings include everything from ISO 13485 Design Controls, ISO 14971 Risk Management, through to verification and validation activities. A successful consumable diagnostics CMO is able to manage established timelines and balance innovations within the development process.
Furthermore, the streamlining of this process allows for the faster development of the final product; this idea is illustrated in the figure below:
Figure 2: Product development cycle
Figure 2 compares a typical product development cycle to that of Phillips-Medisize, a CMO that is experienced in producing successful consumable diagnostic products. In the latter case, there is significantly more overlap between development and manufacturing. These gains are the result of strategic requirements and a strict process/product development process. In additional to this increase in overlap, it is also important to note that both the development and manufacturing curves are more narrow – indicating less time. Looking at development curves specifically, the second curve present in the typical product development cycle (top) has been completely eliminated in the model Phillips-Medisize cycle (bottom). With a more collaborative effort from the early design stages, there is less need for costly and time-consuming changes in later stages; with this iterative procedure of late design improvements and implementations effectively removed, we arrive at a more streamlined and efficient process.
Summary
The increase in complex consumable products effectively translates to an increase in CMO opportunity. However, not all CMOs will be able to successfully participate in this space; to be a successful diagnostic consumables CMO there must be competency across all relevant technical disciplines and end-to-end integrated service solutions – all built on a foundational understanding of the market. As was illustrated by the case study, the model product development cycle cannot be fully achieved with technical competencies alone. Rather, these technical competencies must always be accompanied by end-to-end operations. A successful diagnostics consumable CMO can effectively apply both concepts for every manufacturing project.