Tuesday, January 29, 2019
TYPES OF TRANSFERS OF ANALYTICAL PROCEDURES
TAP can be performed and demonstrated by several approaches. The most common is comparative testing performed on homogeneous lots of the target material from standard production batches or samples intentionally prepared for the test (e.g., by spiking relevant accurate amounts of known impurities into samples). Other approaches include covalidation between laboratories, the complete or partial validation of the analytical procedures by the receiving unit, and the transfer waiver, which is an appropriately justified omission of the transfer process. The tests that will be transferred, the extent of the transfer activities, and the implementation strategy should be based on a risk analysis that considers the previous experience and knowledge of the receiving unit, the complexity and specifications of the product, and the procedure.
Comparative Testing
Comparative testing requires the analysis of a predetermined number of samples of the same lot by both the sending and the receiving units. Other approaches may be valid, e.g., if the receiving unit meets a predetermined acceptance criterion for the recovery of an impurity in a spiked product. Such analysis is based on a preapproved transfer protocol that stipulates the details of the procedure, the samples that will be used, and the predetermined acceptance criteria, including acceptable variability. Meeting the predetermined acceptance criteria is necessary to assure that the receiving unit is qualified to run the procedure.
Covalidation Between Two or More Laboratories
The laboratory that performs the validation of an analytical procedure is qualified to run the procedure. The transferring unit can involve the receiving unit in an interlaboratory covalidation, including them as a part of the validation team at the transferring unit and thereby obtaining data for the assessment of reproducibility. This assessment is made using a preapproved transfer or validation protocol that provides the details of the procedure, the samples to be used, and the predetermined acceptance criteria. The general chapter Validation of Compendial Procedures (1225) provides useful guidance about which characteristics are appropriate for testing.
Revalidation
Transfer Waiver
The conventional TAP may be omitted under certain circumstances. In such instances, the receiving unit is considered to be
qualified to use the analytical test procedures without comparison and generation of interlaboratory comparative data. The
following examples give some scenarios that may justify the waiver of TAP.
• The new product’s composition is comparable to that of an existing product and/or the concentration of active ingredient
is similar to that of an existing product and is analyzed by procedures with which the receiving unit already has experience.
• The analytical procedure being transferred is described in the USP–NF, and is unchanged. Verifiction should apply in this
case (see 1226).
• The analytical procedure transferred is the same as or very similar to a procedure already in use.
The personnel in charge of the development, validation, or routine analysis of the product at the transferring unit are
moved to the receiving unit.
If eligible for transfer waiver, the receiving receiving unit should document it with appropriate justifications.
ELEMENTS RECOMMENDED FOR THE TRANSFER OF ANAYTICAL PROCEDURES
Several elements, many of which may be interrelated, are recommended for a successful TAP. When appropriate and as a
part of pretransfer activities, the transferring unit should provide training to the receiving unit, or the receiving unit should run
the procedures and identify any issues that may need to be resolved before the transfer protocol is signed. Training should be
documented.
The transferring unit, often the development unit, is responsible for providing the analytical procedure, the reference standards,
the validation reports, and any necessary documents, as well as for providing the necessary training and assistance to the
receiving unit as needed during the transfer. The receiving unit may be a quality control unit, another intracompany facility, or
another company such as a contract research organization. The receiving unit provides qualified staff or properly trains the
staff before the transfer, ensures that the facilities and instrumentation are properly calibrated and qualified as needed, and
verifies that the laboratory systems are in compliance with applicable regulations and in-house general laboratory procedures.
Both the transferring and receiving units should compare and discuss data as well as any deviations from the protocol. This
discussion addresses any necessary corrections or updates to the final report and the analytical procedure as necessary to reproduce
the procedure.
A single lot of the article may be used for the transfer, because the aim of the transfer is not related to the manufacturing
process but rather to the evaluation of the analytical procedure’s performance at the receiving site.
PREAPPROVED PROTOCOL
A well-designed protocol should be discussed, agreed upon, and documented before the implementation of TAP. The document
expresses a consensus between the parties, indicating an intended execution strategy, and should include each party’s
requirements and responsibilities. It is recommended that the protocol contain the following topics as appropriate: objective,
scope, responsibilities of the transferring and receiving units, materials and instruments that will be used, analytical procedure,
experimental design, and acceptance criteria for all tests and/or methods included in the transfer. Based on the validation data
and procedural knowledge, the transfer protocol should identify the specific analytical performance characteristics (see 1225 and 1226) that will be evaluated and the analysis that will be used to evaluate acceptable outcomes of the transfer exercise.
The transfer acceptance criteria, which are based on method performance and historical data from stability and release results,
if available, should include the comparability criteria for results from all study sites. These criteria may be derived using
statistical principles based on the difference between mean values and established ranges and should be accompanied by an
estimation of the variability (e.g., percent relative standard deviation [%RSD] for each site), particularly for the intermediate
precision %RSD of the receiving unit and/or a statistical method for the comparison of the means for assay and content uniformity
tests. In instances of impurity testing, where precision may be poorer such as in the case of trace impurities, a simple
descriptive approach can be used. Dissolution can be evaluated by a comparison of the dissolution profiles using the similarity
factor f2
or by comparison of data at the specified time points. The laboratories should provide appropriate rationale for any
analytical performance characteristic not included. The materials, reference standards, samples, instruments, and instrumental
parameters that will be used should be described.
It is recommended that expired, aged, or spiked samples be carefully chosen and evaluated to identify potential problems
related to differences in sample preparation equipment and to evaluate the impact of potential aberrant results on marketed
products. The documentation section of the transfer protocol may include report forms to ensure consistent recording of results
and to improve consistency between laboratories. This section should contain the additional information that will be included
with the results, such as example chromatograms and spectra, along with additional information in case of a deviation.
The protocol should also explain how any deviation from the acceptance criteria will be managed. Any changes to the transfer
protocol following failure of an acceptance criterion must be approved before collection of additional data.
THE ANALYTICAL PROCEDURE
The procedure should be written with sufficient detail and explicit instructions, so that a trained analyst can perform it without
difficulty. A pretransfer meeting between the transferring and receiving units is helpful to clarify any issues and answer any
questions regarding the transfer process. If complete or partial validation data exist, they should be available to the receiving
unit, along with any technical details required to perform the test in question. In some cases it may be useful for the individuals
who were involved with the initial development or validation to be on site during the transfer. The number of replicates
and injection sequences in the case of liquid or gas chromatography should be clearly expressed, and, in the case of dissolution
testing, the number of individual dosage units should be stipulated.
TRANSFER REPORT
When the TAP is successfully completed, the receiving unit should prepare a transfer report that describes the results obtained
in relation to the acceptance criteria, along with conclusions that confirm that the receiving unit is now qualified to run
the procedure. Any deviations should be thoroughly documented and justified. If the acceptance criteria are met, the TAP is
successful and the receiving unit is qualified to run the procedure. Otherwise, the procedure cannot be considered transferred
until effective remedial steps are adopted in order to meet the acceptance criteria. An investigation may provide guidance
about the nature and extent of the remedial steps, which may vary from further training and clarification to more complex
approaches, depending on the particular procedure.
Yours Chromatographically
#KZ
