Enzyme suppliers can assist in this process by working with customers to develop superior products, for example with higher activity or in different formulations, which enable improved assay performance.

Tests for novel diagnostic markers may require the development of new enzymes. IVD manufacturers may wish to collaborate with enzyme suppliers that provide a custom development service.

The pricing of today’s recombinant enzymes is largely driven by the scale of the fermentation hence if the demand volumes increase then there should be a concomitant decrease in pricing. Aside from volume, technical advances such as optimised vectors producing increased expression levels, greater control of protein folding and glycosylation levels, and the secretion or compartmentalising of functional enzymes to make harvesting easier should all combine to drive down the costs of production. However enzyme manufacturers will have to account for substantial research & development costs to overcome such technical hurdles so while a significant reduction in the pricing of recombinant enzymes is on the horizon it is unlikely to take place in the near future.

Experience of supply into market is also a must. Working with a supplier who understands the demands of IVD manufacturers and already supplies products with proven performance leads to fewer supply chain issues.

One size doesn’t fit all. A supplier should be flexible and have the capability to work with IVD manufacturers to develop bespoke products, along with customised analytical testing procedures.

Once you have found such a supplier, you want to know that they will prove to be reliable. Continuous supply and short lead times are critical. Ensure you are comfortable with their capacity and ability to source vital raw materials.

It is fair to assume that the IVD Directive more specifically covers the hazards related to IVD instruments and therefore the Machinery Directive does not apply to IVDs as such.

For other medical devices, the situation is clarified in revision 2007/47/EC of the Medical Devices Directive 93/42/EEC itself and an interpretative document (reference ENTR/F/3/PBE/pdw D (2009) 27250).

Medical devices that are machinery have to comply with the Medical Devices Directive and follow the appropriate conformity assessment procedure from that directive. However, when the Machinery Directive’s Annex I contains health and safety principles that are more specific for relevant hazards of the machinery under consideration, these health and safety principles (and any associated harmonized standards) shall also apply and be addressed in the conformity assessment of the medical device.

Although a similar explicit guidance does not exist for IVD, this approach is appropriate for IVDs too.

Answer provided by Dirk Stynen, PhD, who is President and Principal Consultant at Qarad. He has more than 20 years of experience in the IVD industry and held functions in R&D, quality assurance and regulatory affairs. He can be reached at dirk.stynen@qarad.com

Precept Medical Products Inc. (www.perceptmed.com), Bioclinica (www.bioclinica.com), and Atlantis Plastics Inc.

The importance of following a structured and careful process for selecting a competent contract manufacturer cannot be understated.  Contract manufacturing relationships tend to be long term, and making a change in suppliers is extremely difficult once started.  There are many tools available both online and offline to find contract manufacturers within your domain area. The following list is not in any order of preference. One, several, or all of these options can be utilized in your search.

• Obtain references from companies using contract manufacturers in similar domains. 

• Supplier portals such as Global Spec, ThomasNet, etc.

• Networking within relevant associations and industry events.

• Online research.

• Attend trade shows that attract contract manufacturers.

• Advertisements in trade newsletters.

Once manufacturers find them, what is the main requirement for selecting the appropriate contract manufacturer (CM)?

Depending upon the type of project that you have, there are various requirements to evaluate in your selection process. The following list are requirements for you to consider when interviewing contract manufacturers for your project.

• Track record. Does the CM have a strong history of delivering quality products on time?  Do they have strong relationships with current customers.  Ask for and follow up with references.  Conduct on-site visits. 

• One stop shop. If possible, select a partner that will succeed in your company’s manufacturing environment generally, not for just a single project.  The outsourced partner selection process is simply too time-consuming to repeat for every single development or manufacturing effort.

• Cultural fit. Make sure to visit the CM’s facilities and be confident that you can build a good working rapport and share business values with the key members of the team you’ll be working with including the supply chain manager, quality manager, finance manager, operations manager, project leader, and executive leadership of the company.

• Competence. Does the CM have the technical capability and expertise manufacture/pack/test the product(s) in question?  For example, one of the typical attributes in a CM that is often overlooked in the CM selection process is the CM’s ability to conduct R&D.  Selecting a CM with R&D capabilities provides many key advantages.  The following are a few:

          If the CM has R&D capabilities, they will be comfortable and conversant in a development culture, which will dramatically improve their communication with your R&D team    and speed your time to market through the transition into manufacturing.

          They will be able to act on your behalf (if desired) in evolving a product once in production (Design for Cost, Serviceability, Assembly, etc.), while having the internal processes necessary to ensure that changes don’t adversely affect function.

          On future products you will have the ability to add bandwidth to your internal R&D team for shorter term resource needs without adding permanent headcount to your company’s staff. 

• Quality. Does the CM comply with the quality standards required to manufacture your product?

• Capacity. Does the CM have the capacity to meet sales demands both near and long term?

• Concentration. Will your business represent too large or too small percentage of the CM’s total business?

• Cost. Can the CM supply the product cheaper than in-house production or competitive suppliers?

• Business health. Is the CM a secure and thriving business capable of being a long-term supplier?

• Supply chain. Does the CM regularly source commodities associated with your product?  Do they have a strong supply chain both domestically and off-shore?

• Controls. Does the CM have internal methods of regularly providing comprehensive, accurate and timely information?

• Technology. Is the CM’s technology infrastructure up to date?

• Finances. Does the CM have the financial capability and sufficient cash to handle your business?

• Customer service. What is the CM’s track record in this area and what infrastructure do they have to record, track and solve problems and ensure you are a satisfied customer?

·Have both parties sign a mutual NDA.

·Ensure there is no conflict of interest between the client and the contractor.

·Verify that the contractor’s internal employment agreements with their own employees and contractors bind them to the appropriate terms of confidentiality.

·Verify that the contractor’s internal IT systems secure the working files such that only those resources working on the project have access to these files.

·Verify that the contractor’s IT systems include state of the art firewalls and disaster recovery plans.

·Agree on code names for all projects and documents.

·Request that the contractor perform the work in a secured area limited to only those working on that project.

·Consider resource exclusivity to restrict personnel from working on other projects in a similar domain.

·Consider entering into an exclusivity agreement restricting the contractor’s ability to work with certain competitors for a period of time.

·Ensure contractor communications with external suppliers is bound by the appropriate level of confidentiality.

·Limit sensitive work to be conducted on-shore in a single location rather than spread across multiple global locations.

Positioning accuracy. There are three distinct issues:

1. Positioning with a stepper is open-loop, as seen by the motor controller. In circumstances such as a jam the motor can fail to reach commanded position (”skip steps”). This failure is invisible to the controller, so subsequent positioning will also be wrong. DC servo motors are used with rotary encoders, which ensure reliable feedback of shaft angle.

 2. DC servo motor encoders typically generate 500 pulses per revolution or more. Quadrature decoding provides 4X improvement, ie. to 2000+ counts per revolution. Steppers used in positioning typically have 200 steps per revolution. Microstepping improves this figure, however not to the positioning accuracy achieved by a typical encoder.

3. Once stopped a stepper motor does not stay parked exactly at its nominal step position if disturbance torque is present. Rather it deviates from that position so as to generate restoring torque. This deviation is invisible to the controller. DC servo positioning systems typically also have position error in the presence of a disturbance torque. However this error is visible to the controller and can be addressed via explicit control techniques, such as integral feedback, if necessary.

Shaft speed

Steppers typically operate at hundreds of RPM, depending on supply voltage and other particulars. DC motors can go beyond 10,000 RPM.

Power versus package size

The size of a motor reflects how much torque it can produce, not power. So in general the faster shaft of the DC motor provides greater power for a given size. This is especially true when this power is required in the form of short bursts of high torque, such as to accelerate the inertial load in a high-performance positioning system. Torque demanded of a stepper must be kept safely below its nominal maximum to avoid skipping steps. In contrast, a DC motor can be over-driven to many times its continuous torque rating for short durations.