BBInternational (Cardiff, UK)
 |
The Isoflow Bench Top Reagent Dispenser by Imagene Technology (Hanover, NH).
|
For example, how much flexibility will be required throughout the product’s manufacturing life cycle—determined by whether or not the assay is highly technical and may require modification along the way—will speak to suitability of the proposed materials and equipment for the purpose. A highly technical platform may require of suppliers a different sort of service level or development input than is usual. Platform technicality colors the question of how closely the manufacturer should work with its suppliers. How well the long-term company budget accommodates the anticipated commercialization of a new IVD device will be a factor in determining which manufacturing equipment options should be considered initially. Expectations for long-term throughput and the nature of any scale-up plan are key decision-making factors; proposed capital purchases should suit the prospects of the job as a long- or short-term project. Also, the degree of product quality assurance the target markets will demand is important. Any manufacturing equipment and supplies purchased will have to support fulfillment of those requirements.
Selecting Manufacturing Partners
The most practical way for an IVD manufacturer to ensure that all bases are covered is to begin discussions with potential suppliers as soon as possible. Over the long term, the supplier of any kind of manufacturing equipment will become almost as familiar with the production process as the in-house team, so its representatives should be on board the project at a very early stage. A strong supplier will be knowledgeable in many technical areas and may well be able to provide input regarding the science involved in the product conception. Such a supplier will have acquired a wealth of experience through developing projects much like that of its prospective customer. This sort of resourcefulness will be particularly beneficial to IVD companies just getting into manufacturing. The supplier should offer the manufacturer guidance and training significantly beyond the basic training provided when the equipment is delivered.
The role of the supplier includes guiding the manufacturer through the entire process development project that results in a finished device. Ongoing discussions and regular meetings should identify any concerns or problems immediately as they arise, and will ensure an open dialogue between all members of the development team. An equipment supplier that is involved early enough may be able to suggest ways of altering the assay design so that it will be more amenable to an automated manufacturing process. This can be particularly beneficial with FDA-regulated products, as it can minimize the need for design changes or revalidation later.
A strong relationship between the equipment supplier and the manufacturer established at the beginning gives assurance to the IVD company that both equipment and support will be there when needed. This is very important for longer-term production runs and particularly relevant when the capital equipment or associated components might be customized or complicated. Equipment development can be time-consuming and costly at the best of times; things will only be harder if the supplier is not fully on board and cooperative.
At the time of selection, the IVD manufacturer may decide to engage a supplier that offers an extensive range of products and services, as this may increase response flexibility as the project develops. Importantly, there may be no need to use several suppliers, even as changes occur. Strong case history files the supplier has accumulated will be useful to the manufacturer. These may cover areas not strictly related to the capital purchase, such as assay design capability, production consumables, or machine staffing levels. Equipment for rapid-test manufacture, for example, will have been developed over many years. Many man-hours of refining and troubleshooting will likely have culminated in an efficient, reliable, and cost-effective piece of machinery with few associated risks. The supplier’s delivery lead time should be good because an established customer base will be generating throughput.
Also, the supplier will be an excellent advice source because of its deep knowledge of the manufacturer’s specialist field. This is especially relevant if the supplier operates in a number of other related areas; for example, the supplier may already be involved in test development and manufacturing as part of its business. It may already use the equipment as part of its everyday operation and so will be forthcoming about the deficiencies of the equipment under review. In addition, the supplier may be able to share information that will be beneficial for working out the economics of operation, about which more later.
Early Planning
Once the IVD manufacturer’s project team is established, the advance planning can commence. This essential planning process should not consider the piece of equipment in isolation; rather, it should include the entire production operation, from dispensing the reagents right through to packaging the finished item.
Scale-up is key, and should be another early consideration. An easy mistake is to look at this much later in the process. But early definition will result in a smoother scale-up, and may result in cost savings if it prevents the purchase of unnecessary equipment, as it should. With initial production batches, for example, hand assembly or a very basic automation system may effectively serve the purpose. Later, however, when the assay has been well received by the market and is being launched in new territories, fully automated production may be essential. Ideally, the same supplier should be able to provide options both for the early equipment for initial market launch and for the scaled-up equipment to handle the larger volume of output once the product is fully commercialized. This will bring a desirable level of consistency to the process and may help to minimize verification issues.
It is also important to establish early on the degree of customization the IVD product will require of its associated capital equipment. At first consideration, an equipment purchase might seem relatively straightforward; however, once the project team has fully evaluated the assay, they may conclude that an investment in customized equipment is necessary to cope with certain unusual requirements the platform may present. This could involve extensive engineering or further machinery design and development that could translate into a larger expenditure and longer lead times than originally anticipated. Good early planning, though, might allow the inclusion of some standard components and technologies. But because the process of quoting and defining specifications for more-specialized machinery can take time, all dialogue relating to this should commence in the early stages.
Project meetings should be used to clarify requirements from the very beginning. If technical changes are made to the assay later, once it has moved into the manufacturing phase, changes may need to be made to the manufacturing equipment as well, which could lead to spiraling costs and longer timelines. As IVDs become more advanced, the equipment to manufacture them will have to develop accordingly. New targets and methods and more-diverse applications for the product will have a significant impact on the manufacturing process, and project team discussions can help to identify the effect of these advances on manufacturing requirements.
Economic Efficiency
Value for money in manufacturing equipment encompasses far more than simply what is received for the capital expenditure. The machine’s performance, including values assigned to its reliability, utility, and throughput, is a factor in determining its long-term cost-efficiency. To illustrate, the degree of simplicity or complexity of the equipment will have a future financial impact to the extent that it will increase or reduce operator errors. Furthermore, simple machines that allow in-house staff to perform on-site repair will keep manufacturing downtime to a minimum. The machines’ ease of use will be additionally economical in that equipment that is straightforward to set up and clean down will require less hands-on time from operators, thus facilitating line changes and increasing overall productivity.
Another important economic consideration is the amount of material wastage that will occur during production because of the equipment design. Wastage can be, for example, the dead volume of reagents required to prime a system, or usable material that is discarded because of manufacturing process efficiencies. Reagents can be among the most costly product components, so it is worthwhile to investigate this issue in advance. Wastage that may seem negligible in small production batches will increase alarmingly upon scale-up. Again, it is always advisable to think long term and look at the bigger picture.
Prior to committing to any form of capital expenditure, an IVD company should draw up detailed financials that include a realistic payback calculation of how many assays need to be manufactured to pay for the equipment. Comparisons with the payback for outsourcing manufacture and with the cost of hand assembly should be included. This cost comparison should form part of an ongoing monitoring of the investment to ensure continued value, taking into account factors such as regular maintenance and renewal of consumable parts, repairs, and unforeseen technical problems. In order to get an accurate assessment of payback rate, company managers might best speak to existing users of the equipment. They should not be hesitant to ask for contacts in noncompeting businesses from whom they could obtain feedback.
If the company has a genuinely strong relationship with its supplier, then it can be confident that the equipment builder will present a realistic account of cost-efficiency. Even better, if the IVD firm is working with a supplier that has firsthand operational experience of the equipment, using it for its own assay manufacture, then it can expect to receive an accurate evaluation and detailed run-rate information that will allow for a highly informed decision. That supplier will have gathered extensive industry contacts, and may well know of component and raw material suppliers whose products are highly complementary to the manufacturing equipment in question.
Quality Assurance
Early discussions between the equipment supplier and purchaser should commence with the signing of a nondisclosure agreement designed to protect both parties’ interests in systems and proprietary information throughout the project, or to cover a sufficient period of time should an alternative supply option be chosen. Once the primary supplier has been agreed upon and a contract signed, the purchaser may wish to investigate potential secondary supply sources as a contingency plan should there ever be a failure in supply—or, indeed, in the working relationship with the primary supplier. This backup planning should not be limited to capital purchases only. It is a strategy useful also for securing a regular supply of all essential production components and raw materials.
Another early consideration is the level of product quality assurance desired. As the IVD market becomes increasingly regulated and competitive, it is essential that the device manufacturer find suppliers whose processes are in synch with its own in terms of providing traceability, maintaining a consistent high level of product quality, and satisfying regulators. The parts of the machine should be well manufactured and fully calibrated. The equipment purchaser will want to know what sort of inspection systems were used and what level of ongoing auditing was carried out during machine construction. Also, should documentation of such activities be required in the future, the purchaser should know whether it will have full access to those materials. The IVD manufacturer should establish early on that any available audit trails will be maintained at the standard that a future inspection or regulatory submission may require. Again, this level of scrutiny should not be limited to the capital equipment purchase alone; indeed, a total quality system approach may be more beneficial.
Finally, when looking at the quality aspect of any supply arrangement, the purchaser should set the performance parameters early on. Should there be any problems with the equipment, or indeed with the finished article in the future, the degree to which the machinery supplier will be held accountable should be established. In other words, if the finished test is faulty, will the machinery supplier be expected to work with the manufacturer to solve the problem, or will the measure of performance be based specifically and strictly upon the equipment’s operation rather than its relation to the finished product? The IVD manufacturer should make sure that responsibilities and requirements are defined from the outset, so that both parties can continue to work in partnership and address any problem areas or further development needs, when they arise, as a team.
The IVD industry continues to become more competitive with respect to both pricing and the race to develop the next generation of sophisticated devices. By working closely with its suppliers, a manufacturing company can be assured that its investment in capital equipment will pay off in the long run, in terms of quality, performance, and profitability.
