Transferring a pre-existing method (if not defined by a pharmacopeia) or establishing a new method often requires a technical
feasibility study or trial run, which allows the CRO to provide a proof of concept of the intended method. The reagents or
methods supplied by the customer can be checked and any supplementary consumables or equipment found to be necessary to produce
a robust method, considered fit for purpose, can be sourced. This process allows for an assessment of the typical time constraints
for performing the testing. If the initial projected timelines appear unrealistic, contract or protocol amendments can be
made at this stage.
If the outcome of the feasibility assessment is favorable, then the data can be securely transferred to the customer for approval,
and results may be formally documented in the form of a feasibility report if required.
In this case study, a two-week feasibility project was performed for assays that had not been developed previously. In the
case of customer-established methods transfer to the CRO, this time was used to test the methods and perform comparative data
analysis with the customer's previously derived in-house data. Once the customer was satisfied with the trial and feasibility
tolerances and agreed acceptance criteria, the project could proceed.
A CRO must have the requisite experience in performing rapid methods development, validation, and transfer, and routine sample
testing. In this case study, the CRO had 15 years of experience in developing, establishing, and routinely operating these
types of assays. Time efficiencies often can be introduced during method transfer by planning hands-on training in advance
in the receiving laboratory. This is not always necessary but can be advantageous because any geographic, environmental, or
analyst variation between the two laboratories can be quickly accounted for by doing so. Experience has shown that when biological
products are involved, even fully validated assays and products are often not as robust as initially perceived when transferred
to another laboratory.
The CRO also must be up to date with the latest regulatory requirements. In this case study, the parameters and acceptance
criteria for validation and acceptable inter-laboratory variation limits for the comparative analysis for method transfer
were discussed with the client before initiation. Recommendations were made to the customer and regulatory support was offered.
It is vital that development, validation, and transfer protocols are scrutinized, agreed, and signed off by all concerned
parties before the initiation of the practical aspects of the project.
As the project progressed, both organizations kept each other informed on a weekly basis, and at critical times, on a daily
basis, which meant that any last-minute amendments to the method could be incorporated quickly and unexpected results could
be acted upon immediately. A flexible working approach and service provision is necessary when dealing with such high-priority
projects. The CRO was therefore enabled to react quickly to the client's needs and allocate resources to the project as required,
becoming an extension of the customer's team.
Another advantage in outsourcing to a CRO is that the tools and systems are already in place for analysis. Extensively validated
software (e.g., laboratory information management systems for sample traceability), fully 21-CFR–compliant instrumentation software, and spreadsheets for data analysis can be quickly adapted to produce a flexible data
format per client needs. Analytical and report templates are also available.
Experienced teams for quality assurance checking of data were deployed at critical time-points so that analyses could be checked
immediately as results were produced, and teams for checking and reviewing produced documents were set up at the client site
to enable fast turnaround for document approval. The customer was satisfied and assured that their project tasks and reporting
had been carried out to the appropriate level of science, quality, and integrity.
As the CRO–client relationship grows, the CRO acts as an extension of the client's business. The CRO becomes a stakeholder
in the well-being of the client's business objectives.
In the case study discussed, the CRO delivered the projects on time and within budget. The CRO–client relationship overcame
the many problems posed with obtaining equivalent materials, equipment for the methods-transfer exercises, and many changes
to the project scope after initiation.
Even after the customer has obtained marketing authorization, the CRO testing facility should remain available and flexible
to allow for variability in production times during the manufacturing process, allowing the customer to meet its manufacturing
objectives. This is of course within the remit of the CRO's quality system and customer's product license stipulations. For
example, to support a client's production process, the CRO may need to work odd hours (night shifts) to provide urgently required
real-time data necessary for the client to progress to the next manufacturing stage of the product.
The continued relationship increases the opportunity of a mutual understanding of the issues that can arise and further develops
trust between the two organizations. This may lead to a more collaborative approach with joint planning and forecasting.
The CRO may get the opportunity to become a preferred supplier for manufacturing support and batch release testing. Once the
relationship has reached this stage, an ongoing contractual agreement to cover all testing may be set up and the CRO can organize
work from the customer to give assurance that its testing is centrally placed in its testing schedule.
Building a good working partnership between the client and CRO and maintaining this ongoing relationship results in time and
cost savings, providing added value to both businesses.
Emma Waite is a biomanufacturing support manager at Tepnel Pharmaceutical Services, Livingston, UK, +44 (0) 1506424270, firstname.lastname@example.org