The list of components required for IVDs ranges from the most simple to the
highly complex. Regardless of whether the component falls into the former or
latter category, all of the materials used, from buffers and antibodies through
to the most highly complicated conjugate can significantly affect the
performance of the finished device.
It is therefore essential to invest a significant amount of time at the front
end of the sourcing exercise. In order to provide a stable and reproducible
product a full and exhaustive validation of all components and potential
suppliers must be executed.
Quality Assurance and Commitment to the Customer
Quality governs every aspect of the IVD industry, and it should impact on
every aspect of the vendor’s business. The vendor should not only have in place
their own stringent procedures, but should be receptive to and compliant with
those of the purchaser.
A company’s quality policy should provide a framework for establishing and
reviewing quality objectives, enabling the company to maintain a reputation for
excellence. Quality policies should be consistently reviewed and updated so that
standards are always the best they can be, and up to date with those of the
industry. Should complaints arise they should be responded to immediately;
similarly, vendors should be receptive to customer input as part of a continuous
programme of improvement.
A company’s accreditations will give an initial indication of commitment to
quality. Frameworks should be built on ISO 9001, and GMP standards should be
reflective of the FDA’s requirements. The Quality Control procedures of any
vendor should be based on strict protocols, with documentation openly available
for customer review. QC systems should control the use of any approved suppliers
by the main vendor, and raw materials included within the product must be fully
qualified and accompanied by Certificates of Analysis where required.
The vendor should exercise an open door policy regarding external audits,
along with documentation that satisfactorily states that components used meet
the necessary requirements. As with the review of quality policies, audits
should also form part of an ongoing review of the vendor, rather than an initial
consideration to check off the list.
decision on the supply contract will be the level of accreditation that the
finished product will achieve. A product applying for FDA approval will bring
with it an entirely new set of criteria, which again must be considered early
on. The FDA will require a full back up plan for the continual supply of the
product, and will frequently specify a dual site manufacture facility, for
Another important requirement is for the supplier to agree to notify its
customers of changes in the processes that it uses for the products that it
supplies to them. This should be written into the Supply Agreement, and such
notification of change will allow the customer to assess the impact of the
changes on its processes.
Partnership & Ongoing Support
Researching the market thoroughly to identify vendors with a strong
reputation for delivering high quality products will lead to fewer risks in the
long term. A well established supplier with a proven track record who can
qualify their ability to carry out your requirements is key. A company with many
years’ expertise in their specialised field should not be underestimated when
choosing whether to manufacture reagents in house or not. It is often
highlighted that, in the manufacture of rapid tests, for example, a company
wouldn’t simply manufacture its own membrane, or housing. However, when it comes
to reagents, a common misconception is that the manufacture of raw materials is
a quick and easy cost saving process. This is far from the case, and development
teams frequently experience endless problems further down the line, when finally
there is no choice but to call on the expertise of a good vendor to undo the
damage. By this point, however, the time and costs incurred cannot be
The vendor will have worked through various process many times, and their
expertise will prove invaluable to the present and future working relationship.
A good supplier will work with the purchaser over many years to continually
optimise the product range. Troubleshooting will be carried out in partnership,
and regular communication will ensure that the ongoing supply needs of the
purchaser are met at all times.
Flexibility of Supply
Flexibility is key to anyone working within the industry, as the market
evolves and grows at a tremendous pace. A range of services should be available,
which fit the demand of the purchaser, and not the other way round. A smaller
customer, for example, will have a different set of requirements than a larger
organisation, and a more modular approach to supply and costing may be more
effective. The product too must be fitting with the – often unanticipated –
requirements of the customer, and here BBInternational refer back to the issue of quality. Only the
most stable products can be stored for any length of time, and these will be
needed when the market brings a sudden increase in demand. A good quality source
will support any unexpected sales spikes, although the vendor would clearly
appreciate an approximate forecast of potential demand from the outset.
Once a good vendor is appointed, a committed team of representatives should
work alongside the purchaser at all times, and will not comprise a high turnover
of new faces. A partnership approach is essential to the success of any
supplier/customer relationship, as it brings with it a number of benefits, not
only for the supply in question. An experienced supplier will have its finger
firmly on the pulse of new trends and developments, and will be able to share a
wealth of industry knowledge, and keep customers up to date with emerging
technologies. The company will probably be developing the next generation of
product, and the benefits of this will be passed on to the customer. The vendor
will most likely be able to offer other significant services and advice on
general industry issues such as patent protection or regulatory, for
Most significantly, the vendor should always be able to protect the purchaser
from the perils of single source supply. In an ideal world, all suppliers would
be able to offer a secondary facility that could be utilised in the event of
site one failing to deliver. However, this frequently isn’t the case, and supply
covering significant volume should be subject to some sort of contingency plan,
in case of failure to supply.
Protecting Supply: the Mechanics of ESCROW
When you consider that the raw materials are critical to the performance of
the diagnostic, it’s important to look at ways of protecting this supply. As
many raw materials are manufactured using a proprietary technique, it is often
difficult to establish a second choice of product as the first choice supply is
so unique. Any organisation with an established customer base has a
responsibility to protect their supply source, as any threat of supply will
impinge on the ability to continue with customer development and supply.
ESCROW agreements are a good way of protecting the supply source, and the
methodology of proprietary techniques. Although they can be expensive, they are
a legally binding agreement to protect both parties, and a good vendor should
always be in a position to enter into ESCROW.
Once the customer has established which materials are critical to their
particular process, it’s recommended that negotiations regarding ESCROW
agreements commence. The agreement process requires a fully documented recording
of all the elements of the manufacturing process: the materials used in each
component; the development procedures; details of the machinery used for
manufacture; and complete operating procedures for each individual component. An
independent representative contracted to the customer reviews the specifics of
the manufacturing process, and this legally binding document is then stored
within the safe of an appointed legal organisation.
Specified within the agreement will be the circumstances in which the
agreement can be activated. These circumstances usually include a continuous
failure by the vendor to supply outside of an agreed time period; force majeure,
including flooding or fire; and if the company closes down, or sells to a new
owner who is unable or unwilling to continue the supply. It is likely that the
supplier of the raw material will negotiate that if the agreement is activated,
the customer can only apply the information held within the agreement to their
own application, and cannot share it externally. An additional consideration in
evaluating this kind of agreement is that the vendor should be in a position to
provide good members of staff to train in the correct manufacture of the
materials. Should the ESCROW be activated, training support should be offered to
ensure the exact same processes are utilised.
As a supplier of unique proprietary products, BBInternational has always offered ESCROW agreements to large
volume customers. By detailing our technique in an ESCROW, BBInternational are protecting the customer’s product as well
as our own; if our proprietary formula was not secure, then in the long term our
customers would be left wide open to the threat of their raw materials losing
their unique status.
Qualifying and Validating a Second Source
Should ESCROW not be considered sufficient, a second source supply, or site,
may be required. Again, this offers significant protection, and will be
advantageous from a regulatory perspective. If the product is critical to the
market, then continuation of supply must be guaranteed.
When a second source is qualified, the development process becomes elongated,
extremely thorough, and can be lengthy. For this reason, it is often only
considered by a secondary vendor on a component by component basis against the
original vendor’s ability to supply forecasted volumes, and commitment to long
term supply. A second source vendor will not commence development of any product
using materials still under development by any other supplier, so all materials
in the finished product should be from established product lines, and protected
by supply agreements.
Should a second source require validation, the following considerations
should be taken into account, and actions executed:
· Initially need to complete
a Risk Analysis to identify the impact of material supply change upon test
· Detail the original
material to identify suitable second source materials for evaluation –
composition (cellulose/glass fibre), requirement for chemical treatment
(pre-treatment PVA, BSA, Detergents), physical properties (density, porosity,
tensile strength). Taking into account any limitations or restrictions any
existing packaging may have upon the material requirements for example –
· Evaluate second source
vendor – QA requirements, supply (lead time, volumes), customer support.
· Request samples – multiple
independent manufactured lots and/or limit samples.
· Complete matrix study
swapping in original materials with second source materials and evaluating the
test format on the following issues:
- Compatibility with
- Assembled test format
performance – robustness/sensitivity/specificity.
When evaluating a secondary supply source, because two different
manufacturing processes are evaluated, there is a need for greater robustness in
procedures and the ability to make the product perform under varying conditions.
The upside is that in the long run, the savings are considerable as the second
source can be used if the primary source fails, or if the market requires
Cost is often the primary concern when appointing a supplier, but prior to
making a decision based on cost, an in depth analysis is required.
In house manufacture was previously mentioned as a frequent ‘quick fix’
solution to budget constraints. Similarly, a low cost supplier may deliver the
same initial cost savings. However, further down the line, a badly produced raw
material will lead to significant wastage, for a number of reasons.
In the early stages of the development process, even poor quality reagents
may yield some excellent results. However, once the product is scaled-up, the
result is often an unstable and irreproducible raw material. Such product will
more than likely collapse and put a halt to the progress of the finished device,
wasting significant time as the development process reverts back to the very
beginning. At this point, either another batch of poor quality reagents may be
manufactured, which will likely yield another set of inaccurate results, or the
reagents will be outsourced to the quality supplier who should have been
appointed in the first instance. The quality and supply of the reagent must be
guaranteed from day one, so that at any stage of the development process it is
stable and can be reproducibly scaled up. Without the expertise of good
supplier, this may not be possible.
The instability of poor quality reagents leads them to be very dictatorial
within the development process. For example, in lateral flow, the reagent may
need to be sprayed down very quickly in an effort to prevent it from
de-stabilising. A manufacturing schedule should never be governed in this way,
especially when you consider that an outsourced quality product will help a
development goal or product commercialisation to be achieved in a shorter time
Outsourcing the manufacture of chemical reagents brings with it a whole host
of benefits. It will save on staff training costs, and free up staff to
concentrate on the core competencies of the organisation. It is not a sensible
financial decision for an in-house R&D team to be sidelined into
troubleshooting manufacturing problems with badly produced reagents, as it takes
key personnel away from progressing the project in hand.
A simple cost comparison will clearly lay out the benefits of outsourcing to
a particular supplier, and a good supplier should be able to offer this
transparent service. This, combined with flexible options around bulk purchasing
and supply agreements for longer term savings, should provide a qualified
supplier base that is able to provide the customer with a superior range of raw