If the CAL has not developed and validated analytical methods, then a formal method transfer is required. This transfer determines
the CAL's proficiency in performing the methods. Method transfer should be performed sufficiently in advance of the corresponding
stability study so that the sponsor can fully review the data. Issues with instrument compatibility, data evaluation, and
reporting should be addressed during method transfer. Method transfer precedes and sets the benchmark for the entire stability
study. The sponsor should receive a full report of the data generated so that it may conduct a thorough review.
Analytical method transfer may simply mean that the CAL performs the methods. It may include other aspects such as spiking
samples with additional impurities or degradation products during purity evaluation, linearity, or other qualification analyses.
The analysis should include samples that have higher and lower strength than the product. The originating laboratory and the
CAL should test the same lots or batches of samples, and testing should be within a similar time period so that the samples
are aged to a similar degree. The sponsor establishes the acceptance criteria and issues a certificate of conformance once
it has evaluated the data.
Before the initiation of the stability study, the lead technical staff from the sponsor and CAL should meet to review the
data and results of the analytical method transfer. This review provides the opportunity to evaluate the transfer and address
any problems that arose during analysis or reporting. This opportunity should also be used to review the final stability protocol,
specification requirements, and anticipated timelines to confirm that both parties' expectations are met. Document review
may occur several weeks or months after the original agreement is established, and it is prudent to revisit these items in
case subsequent changes have affected the scope of work or timelines. If the scope of work has increased or timelines shortened,
then the CAL may negotiate to revise the contractual agreement.
The manner in which data are reported is often overlooked, and expectations should be communicated and agreed upon by both
parties. A significant volume of data may be generated early in the process, and several stability reports may be created
during the first 12 months of the study. If the reporting details are not thoroughly established in advance, the stability
reports may need to be reissued, which could potentially compromise the sponsor's ability to evaluate the data properly or
submit regulatory filings within the planned timeframe.
The format of the analytical report should be established during the startup meeting. The sponsor may require the data to
be presented in a specific report format that it provides (e.g., Excel or Word). The sponsor might prefer the CAL's standard
report or require a custom report. If a sponsor's format is to be used, then the CAL's quality-assurance unit may request
a review of the template before the study is initiated. This review ensures that all of the information and references that
the CAL requires are included in the template.
Specifications. The CAL compares the results it generates with the sponsor's specifications. It may use action limits to highlight results
that approach the specification limits. If the sponsor requires an investigation procedure that is different from the CAL's
standard procedure, then specific notification and processes should be described in the study protocol, specifications, or
quality agreement. CALs' investigation processes are generally specific to investigation notification and review process and
typically do not include reanalysis procedures because of sponsors' differing internal policies. Therefore, a sponsor should
specify the particular processes it requires so that the CAL can conform to the sponsor's requirements. The process maybe
listed in the protocol or specifications. The sponsor may choose to provide its own standard operating procedure for investigation
under the confidentiality agreement.
Results that meet specifications but are out of trend should also be considered. For example, suppose the assay specification
is 95.0–105.0%, the initial results are 101.0%, and the three-month results are 97.0%. Although the results are within specification,
the drop in the assay value may be considered aberrant. This interpretation is subjective, therefore clarification may be
required in the specifications.
If the CAL generates and validates the analytical method, then it should ensure that the sponsor is notified of revisions
to analytical methods and other relevant documents. Also, the sponsor should provide the CAL with the most recent versions
of protocols, methods, specifications, and other pertinent documents. The two parties should agree on a chain of custody or
other form of acknowledgement process to ensure that the documents are successfully received and implemented. The sponsor
should also release updated documents at appropriate times. For example, a method release that occurs while the CAL is actively
testing the associated samples will conflict with the effective period of the method. The CAL will have used a method that
is no longer valid, and the sponsor will potentially need to justify how this occurred.