Analytical method transfer

Analytical method transfer
By
Gemmechu.H (B.Pharm, MSc candidate), 2018
7/2/2018 By Gemmechu.H 1
Jimma University,
Institute of Health Science,
SOP, JulaDQ

Outline
Introduction
The drug development process
Types of method transfer
Requirements and elements of analytical technology transfer
Technical transfer time line/project plan
Analysis of results/statistical packages
Analyst certification and training
Transfer of technical ownership

Is the documented process that qualifies a laboratory (the receiving unit) to use an
analytical test procedure that originated in another laboratory (the transferring
unit),
o thus ensuring that the receiving unit has the procedural knowledge and ability to perform the
transferred analytical procedure as intended.
Is the verification that a method or test procedure works in an equivalent fashion
at two or more different sites or laboratories and meets all acceptance criteria.
In short, analytical method transfer qualifies a laboratory to use a test procedure.
 The process is driven by compliance and can be governed by both a statistical and
practical treatment of the resulting data.
Introduction[1]

Introduction[2]
The importance of analytical transfer was underscored by the Analytical Research
and Development Steering Committee (ARDSC) of the Pharmaceutical Research
and Manufacturers of America (PhRMA) during its annual workshop held in
September 2000.
At this meeting, representatives from PhRMA member companies met with
facilitators to draft an acceptable analytical practice (AAP) that can function as
a suitable first step guidance document for conducting successful method transfer activities.
The focus of the AAP is
to provide such guidance and to clarify the essential elements that embody a complete and
compliant transfer.

Table 1 responsibility of Sending Unit and Receiving Unit

The drug development process[1]
Although there are a plethora of internal initiatives targeted at reducing the time
line of drug development and hence the overall time to market, the basic process
of drug development has remained unchanged.
Analytical method evaluation ring test (AMERT) by Crowther, this process allows
the quality unit to make comments and suggestions to their R&D colleagues
before the final validation of the method.
The knowledge base surrounding a compound increases steadily.
At the junction between R&D and operations, it is important to ensure not only
that the analytical methods are successfully used by the quality unit, but also that
the applicable knowledge and data are transferred or are readily accessible by the
receiving laboratory.
Although the quality unit might not require excessive detail regarding all
scientific research performed during the R&D period, some information transfer is
necessary.

The drug development process[2]
Figure 2 the phases of drug development from a clinical perspective.

Types of method transfer
The most common variations of method transfer are
1. Comparative testing,
2. Covalidation between two laboratories or sites,
3. Complete or partial method
validation or revalidation, and
4. Omission of formal transfer processes, sometimes termed the transfer
“waiver.”

1.Comparative testing
It involves two or more laboratories or sites executing a preapproved protocol
that details the criteria by which the receiving laboratory is deemed to be
“qualified” to use the method(s) being transferred.
Requires the analysis of a predetermined number of samples of the same lot by
both the sending and the receiving units
The resulting data are analyzed statistically and compared to the acceptance
criteria.
In pharmaceutical industry other scenarios during development and after approval.
These include alliance partners, CROs, and other internal development groups, for
example, the movement of a project between functional areas or development
sites.

2. Covalidation between Two Laboratories
An alternative to comparative testing is to involve the receiving laboratory in
the validation of the method(s).
By definition, a laboratory or site that performs validation experiments is qualified
to use that method for its intended purpose.
To perform such a transfer, it is necessary to identify which validation parameters
are to be generated or challenged by each partner.
A reasonable approach is to involve the receiving laboratory in the interlaboratory
qualification, thereby generating a matrix of data that summarizes the effect of
testing site, analyst, date of analysis, and instrumentation.
By including these data in the method validation report and fully describing the
experimental design for the validation exercise,
it is possible to have this document stand as proof of the analytical transfer.

3. Method Validation and/or Revalidation
Before the performance of method transfer activities involving protocols and
acceptance criteria, it was customary for a receiving laboratory to repeat some or
all of the validation experiments.
The choice of validation parameter(s) depends highly on the type of method being
transferred.
For example, content uniformity assays to determine consistency of product
potency depend heavily on the method and system precision.
As a second example,
o a determination of trace impurities in an API could not be reproduced between two sites if
their instruments did not yield similar limits of detection and limits of quantitation.

4. Transfer Waiver
Certain situations might certainly warrant the omission of conventional transfer
qualification experiments.
To proceed without some manner of laboratory comparison between the two sites, it is
critical to document the reasons for making such a decision.
For line extensions involving dosage forms that are routinely tested by the receiving
laboratory, it may be possible to waive the transfer for the following reasons:
The receiving laboratory is already testing the product and is thoroughly familiar with
the procedure(s).
The new dosage form possesses either a comparable composition and/or
concentration of API relative to the existing product.
The analytical method(s) are the same as or very similar to those that are already in
use.
The method validation package encompasses the new methods.

Requirements and elements of analytical
technology transfer
Components that necessary to complete a successful comparative
testing transfer includes;
A. Preapproved Test Plan/Standard Operating Procedure/Protocol
B. Description of Methods/Test Procedures
C. Description of Test Requirements
D. Rationale for Test Requirements
E. Acceptance Criteria
F. Documentation of Results

A. Preapproved Test Plan/Standard Operating Procedure/Protocol[1]
Before the planning of any transfer, an approved document that describes both the
general transfer process as well as the specific acceptance criteria necessary for
the method(s) being transferred needs to be in place.
In many companies, it is common for both the R&D and quality units to have
general standard operating procedures (SOPs) that govern the transfer process.
These SOPs describe the details of a method transfer protocol that is specific to
the product and methods.

The contents of such a protocol were,
Clearly define responsibilities of both the transferring and receiving
laboratories
 A list of all methods to be transferred via comparative testing.
Rationale for any methods not included, i.e., transfer waiver, must also be
provided.
The scope of the transfer should be provided with respect to what laboratories
and analysts are affected by the transfer.
In some cases, direct analyst-to-analyst transfer might be necessary due to
method complexity or the use of new or unfamiliar equipment.
The selection materials and samples to be used in the transfer should be
described in detail
A. Preapproved Test Plan/Standard Operating Procedure/Protocol[2]

B. Description of Methods/Test Procedures
It is imperative that copies of all methods used during the transfer are included.
Any validation data that are available should be given to the receiving laboratory.
A difficult method is not necessarily “nonrugged”rather, the developer must
stipulate very carefully the steps that need to be followed and any pitfalls that
might occur.
This can even be the case with compendial methods, which do not necessarily
need to be formally transferred.
Due to the general nature of descriptions of compendial methods, receiving
laboratories often run into difficulty executing them.
In all method procedures, step-by-step directions should be given, including “tips
and tricks,” safety considerations, and clear formulas
and calculations.

C. Description of Test Requirements
As part of the specific transfer, the number of lots, replicates, and injections (in
the case of HPLC) should be expressly presented.
For dissolution transfers, the number of individual dosage forms that will be
tested should be stipulated.
It is necessary to spell out such details so that small differences in the everyday
analytical philosophies do not perturb the transfer process.
In the case of new techniques that may not be common to the receiving laboratory
(i.e., capillary electrophoresis or liquid chromatography/mass spectroscopy),
specific training may be necessary before the execution of a transfer protocol.

D. Rationale for Test Requirements
As in any scientific document, one must provide a rationale for the parameters
chosen and their effect on the overall success of the transfer.
This includes an explanation for the system suitability parameters that have been
established for the method.
System suitability can be a powerful tool for troubleshooting method
discrepancies in addition to being a test of the conformance of the system to a set
of parameters before analysis.

E. Acceptance Criteria
The transfer protocol must include suitable acceptance criteria relevant to the tests and specific
dosage forms.
It should be noted that giving hard and fast specifications for such criteria is not possible.
There would surely be more exceptions than norms.
Below table clearly shows that the discrete acceptance criteria vary considerably from company to
company.
It does illustrate, however, that having systems in place to challenge the performance of a method
during transfer is absolutely required.

F. Documentation of Results
The results of the comparative testing experiments should be documented
in a report summarizing all experiments and results.
Considerable attention must be paid to details of all aspects, observations,
and results of the experiments.
In some cases, the results for the receiving laboratory may not meet the
established acceptance criteria.
Such situations should be addressed by a policy that must be in place to
describe how such data would be handled.
Regardless of whether such a policy is followed, an investigation into all
results that fall outside of the acceptance criteria should be performed and
summarized.

Technical transfer time line/project plan
The time line for formal transfer most often has the process taking place in the middle to late
clinical phase III.
This assumes that the quality unit has given input via sample communication or the AMERT has
taken place.
The timing for the technical transfer must be flexible, depending on the specific product.
It must take into account the need to have methods in place within operations before regulatory
approval or product launch.
One must know that the receiving laboratory has met all criteria to be qualified to perform the
methods and associated testing before the arrival of actual samples.

Analysis of results/statistical packages
The comparative testing type of technical transfer generates results that need to be
compared using one or more statistical tools.
Although one can certainly evaluate the data subjectively, the use of statistics will
build objectivity into the data analysis and allow unbiased comparison of the data
set(s).
Because comparative testing involves destructive testing of individual samples,
the strength of the transfer involves proving mathematically that the data sets are
equivalent.
The complexity of the data treatment is directly related to that of the
method transfer.
Many transfers are governed by the statistics of the standard Student’s t test.

ANALYST CERTIFICATION AND TRAINING
If the personnel in the receiving laboratory do not speak the native language of personnel in the
developing laboratory, translation of the method procedures may be necessary.
It is also important to ensure that proper training of the analysts who will perform the method
procedures has taken place.
There are several options to certify analysts to perform the required test procedures.
One possibility is to qualify individual analysts on each method, thereby creating a matrix of
methods and analysts.
Compliance liability could also result if an analyst who was not “certified”
produced reportable GMP data.
Training records must include documentation that the individual is indeed competent to perform
routine tests using specific transfers.
In these cases, the supervisor or another qualified analyst can certify that the individual analyst is
competent to perform the test procedure in question.
Laboratory Analyst and Training Certification Program (LATCP)7/2/2018 By Gemmechu.H 24

Transfer of technical ownership[1]
At the heart of the technical transfer process is documentation.
The old adage “if it isn’t written, it isn’t done” certainly applies to analytical transfer.
The R&D component of the drug development process encompasses several years, during
which time the knowledge base surrounding a compound increases steadily.
At the junction between R&D and operations, it is important to ensure not only that the
analytical methods are successfully used by the quality unit, but also that the applicable
knowledge and data are transferred or are readily accessible by the receiving laboratory.
Although the quality unit might not require excessive detail regarding all scientific research
performed during the R&D period, some information transfer is necessary.
Rather than inundate the quality unit with a large number of lengthy reports, several concise
documents that meet the specific needs of an operations-based analytical unit are preferred.
In most companies, the most important reports are the method development/validation reports
and analytical development reports.

A. Method Development Report
This report should provide a concise summary of the development of the key
analytical methods used to assure the identity, quality, purity, potency, and
composition of the test article.
For HPLC methods, the rationale for the column and conditions chosen should be
documented.
For discriminating dissolution methods, the choice of media, type of apparatus,
and detection method should be given.
In all cases, a description or tabular list of unsuccessful approaches should be
included.
A good method development/validation report will include sample chromatograms
for approaches that have been tried.

B. Analytical Development Report
The analytical development report is a documented summary and logic flow of all
essential analytical information acquired during the R&D phase of the project.
It is a repository of all important analytical information pertaining to the project
and is
o therefore a source document for the quality unit, and
o it is also used in the preparation of the site inspection at the time of product approval.
All information contained in this report must be traceable to raw data and other
reports, if applicable.
The analytical development report is one of the most valuable documents written
by the R&D unit during the development process.
If properly composed and completed, it can serve as a powerful document for
many years after product approval.

.
Table 2

C. Transfer File
Used as a means of ensuring that all key documents and relevant information are imparted to
operations or the receiving laboratory.
This file is merely a collection of important reports.
For analytical methods, such documents include the method development and validation
reports, impurity profiling report, stability reports and tables, and specification archive.
The power of such an approach is that it ensures that all information is conveyed
to the receiving laboratory.
This strategy is useful if operations will be relied on to continue the development process.
Examples include development for new formulation strengths for “brand support” or life
cycle management or the support of phase IV clinical trials.

References
1. Hand book of modern pharmaceutical analysis edited by Satinder
Ahuja and Stephen Scypinski,volume 3, Academic Press, 2001.
2. Scypinsk S, Roberts D. Acceptable Analytical Practice for Analytical
Method Transfer. Pharmaceutical Research and Manufacturers
Association. MARCH, 2002

Analytical method transfer

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