he transfer of analytical methodology theoretically is arelatively simple operation. In its most common form,analytical method transfer qualifies a laboratory to usea test procedure. The process is driven by compliance

and can be governed by both a statistical and practical treat-ment of the resulting data. Robust transfers begin with vali-dated methods, as described by McGonigle (1). The transfermust be completed successfully for the receiving laboratory toobtain “reportable data,” implying that these data may be usedin a CGxP context.

The importance of analytical transfer was underscored by theAnalytical Research and Development Steering Committee(ARDSC) of the Pharmaceutical Research and Manufacturersof America (PhRMA) during its annual workshop held in Sep-tember 2000 (2). At this meeting, representatives from PhRMAmember companies met with facilitators to draft an acceptableanalytical practice (AAP) that can function as a suitable first-step guidance document for conducting successful method trans-fer activities. The focus of the AAP is to provide such guidanceand to clarify the essential elements that embody a complete andcompliant transfer. The AAP described in this article is intendedto apply to all analytical method transfer activities from all trans-ferring groups and combinations such as R&D to quality, R&Dto R&D, and so forth. This guidance does not apply to microbi-ological methods or to transfers conducted to FDA laboratoriesfor the purposes of method trials connected with regulatorydossier approval.

Types of method transfer Method transfer is defined as the process that qualifies a labo-ratory to use an analytical test procedure. The most commonvariations of method transfer are comparative testing, covali-dation between two laboratories or sites, complete or partialmethod validation or revalidation, and the omission of formaltransfer, sometimes termed the transfer waiver.

Comparative testing. Comparative testing is the most com-mon form of method transfer in the pharmaceutical indus-try. It involves two or more laboratories or sites executing apreapproved protocol that details the criteria by which the re-ceiving laboratory is deemed to be qualified to use themethod(s) being transferred. The resulting data are comparedwith a set of predetermined acceptance criteria. Comparative

84 Pharmaceutical Technology MARCH 2002 www.pharmtech.com

Pharmaceutical Research and Manufacturers Association Acceptable Analytical Practice for

Analytical Method TransferStephen Scypinski, Darryl Roberts, Mary Oates, and Joseph Etse

Stephen Scypinski, PhD, DarrylRoberts, PhD, Mary Oates, PhD, andJoseph Etse, PhD,were chosen by theAnalytical Research & Development SteeringCommittee of the Pharmaceutical Researchand Manufacturers of America (PhRMA) todraft the acceptable analytical practiceguidance document.

TThis articlepresents thecollective viewsof the Analytical

Research & Development SteeringCommittee of the Pharmaceutical Researchand Manufacturers of America (PhRMA)about the topic of analytical methodtransfer. These views were presented duringPhRMA’s annual workshop held inSeptember 2000.

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testing also is used in other scenarios during development andpostapproval, including other manufacturing sites and con-tract research organizations.

Covalidation between two laboratories. An alternative to com-parative testing is to involve the receiving laboratory in the vali-dation of the method to be transferred. By definition, a labora-tory or site that performs validation experiments is qualified torun that method routinely. To perform such a transfer, one mustidentify which validation parameters are to be generated or chal-lenged by the sending and receiving laboratories. A reasonableapproach is to involve the receiving laboratory in the interlabo-ratory qualification, thereby generating a matrix of data thatsummarizes the suitability of the testing site, analyst, date ofanalysis, and instrumentation for exercising the analytical testprocedures. By fully describing the experimental design for thevalidation exercise and including the resulting data in the methodvalidation report, it is possible to have this document stand asproof of transfer of the analytical test procedure.

Method validation and/or revalidation. Another option for ac-complishing method transfer is for the receiving laboratory torepeat some or all of the validation experiments. After valida-tion is completed, the second laboratory is deemed qualified toperform the method. The choice of validation parameter(s) depends highly on the type of method being transferred. Forexample, content uniformity assays to determine consistencyof product potency depend heavily on the precision of themethod.

Transfer waiver. Certain situations might warrant omittingconventional transfer qualification experiments altogether.When a transfer waiver is applied, the receiving laboratory canproceed to use the analytical test procedures under discussionwithout generating interlaboratory comparative testing data.To proceed without generating such data, one must documentthe reasons why this action was taken. Examples of these rea-sons were discussed by PhRMA workshop attendees; they in-clude the following:● The receiving laboratory already is testing the product and is

thoroughly familiar with the procedure(s).● The new dosage form possesses either a comparable compo-

sition or concentration of active pharmaceutical ingredientrelative to the existing product.

● The analytical method(s) are the same or very similar to themethods that are already in use.

● The method validation package encompasses the new meth-ods.

● Personnel who developed the methods move from one siteor laboratory to another as the project evolves.

● The new methods involve changes that do not substantiallyalter the ability to use the method (e.g., changes in samplepreparation procedures or changes in calculation formulas).

Required elements of an analytical method transferThis section presents the various components necessary to com-plete a successful method transfer by means of the compara-tive testing route. As will be discussed, many of the factors nec-essary for a compliant transfer are interrelated.

Preapproved test plan/SOP/protocol. Before implementing any

method transfer, one should set in place an approved documentthat describes both the general transfer process as well as thespecific acceptance criteria necessary for the method(s) beingtransferred. Usually, both the R&D and quality units have gen-eral standard operating procedures (SOPs) that govern the trans-fer process. These SOPs describe the details of a method trans-fer protocol or test plan that is specific to the product andmethods. This document should define clearly the responsibili-ties of both the transferring and receiving laboratories. It alsoshould list all methods that will be transferred. A rationale forany methods not included (i.e., a transfer waiver) also must beprovided.

The selection of materials and samples to be used in themethod transfer should be described. In general, one does notchoose GMP-released materials for transfer activities becausethe results of not meeting the predetermined acceptance crite-ria could trigger an out-of-specification (OOS) investigation.The identity and lot numbers of specific batches should bestated. If possible, certificates of analysis for all samples, in-cluding reference standards, should be supplied. All instru-mentation and associated parameters should be described, in-cluding any disclaiming statements that may affect the outcomeof the transfer. An example of the factors affecting method trans-fers have been described in a classic article by Kirschbaum (3).If possible, the instrumentation should be held constant dur-ing the transfer, thereby eliminating one variable from the pro-cess. Alternatively, it is recommended that the transferring lab-oratory consider running the method on instrumentationcommon to the quality unit before formal transfer.

Description of methods/test procedures. It is important to in-clude records of all methods used during the transfer. Any vali-dation data that are available should be given to the receivinglaboratory. One should include any idiosyncrasies present inthe method. A difficult method is not necessarily nonrugged.Rather, a thoroughly developed method will include the stepsthat must be followed and any pitfalls that may be encoun-tered. In all procedures, step-by-step directions should be pro-vided, including tips and tricks, safety considerations, and clearequations and calculations.

Description of test requirements. As part of the specific trans-fer, the number of lots, replicates, and injections (in the case ofhigh-performance liquid chromatography) should be presentedexpressly. In the case of dissolution transfers, the number of in-dividual dosage form units that will be tested should be stipu-lated. One should spell out such details so that small differencesin the everyday analytical philosophies do not disturb the trans-fer process.

Rationale for test requirements. One should provide a ratio-nale for the parameters chosen and their effect on the overallsuccess of the transfer. This description also should explain anysystem-suitability parameters that already had been establishedfor the method.

Acceptance criteria. The transfer protocol or test plan shouldinclude suitable acceptance criteria relevant to the tests and spe-cific dosage forms. Giving hard and fast specifications for suchcriteria is not possible because a considerable number of ex-ceptions would surely exist. At the recent PhRMA ARDSC work-

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shop about method transfer, participantsdescribed a variety of approaches. Table Isummarizes some of the responses toquestions about acceptance criteria foranalytical methods. The table clearlyshows that the discrete acceptance crite-ria vary considerably from company tocompany. It also shows, however, that hav-ing systems in place to challenge the per-formance of a method during transfer iscommon during the transfer process.

Documentation of results. The results ofthe transfer should be documented in areport that summarizes all experimentsand results. One should pay considerableattention to detail with respect to anyand all aspects, observations, and experimental results. In somecases, results from the receiving laboratory may not meet theestablished acceptance criteria. Such situations should be ad-dressed by a policy that describes how failure to meet prede-termined acceptance criteria should be handled and how theoverall transfer should be affected. PhRMA workshop atten-dees almost were unanimous in stating that failure to meet pre-determined acceptance criteria does not constitute an OOS in-vestigation. Regardless of whether such policy is followed, aninvestigation into all results that fail to meet the predetermined

acceptance criteria should be performed and documented inthe resulting summary report.

Use of statistics in data evaluationComparative testing as a means by which analytical test meth-ods and procedures are transferred from one laboratory to an-other involves the generation of data that can be comparedusing one or more statistical tools. Although one certainly canevaluate the data subjectively, the use of statistics will build ob-jectivity into the data analysis and allow unbiased comparisonof the data sets. Because comparative testing involves destruc-tive testing of individual samples, the strength of the transferinvolves proving mathematically that the data sets are equiva-lent. Many transfers are governed by the statistics of the stan-dard Student t-test (4). The t-test is useful for determiningequivalence of like data sets and is generally sufficient for ana-lyzing data results for comparative testing. A consensus ofPhRMA workshop attendees held that both statistical and non-statistical approaches to data evaluation are acceptable. How-ever, the decision whether to use statistics must be part of thetest plan. It is not acceptable to use only mathematics as a meansto explain a failed transfer.

SummaryThe important aspects of the analytical transfer process as theyrelate to compliance, analytical data, and documentation havebeen discussed in this AAP. This AAP provides guidance forthe performance of method transfer activities that meet regu-latory requirements.

References1. E. McGonigle, “Assay Validation and Interlaboratory Transfer,” in De-

velopment and Validation of Analytical Methods, C.M. Riley and T.W.Rosanske, Eds. (Elsevier, New York, NY), pp. 3–13.

2. Pharmaceutical Research and Manufacturers of America AnalyticalResearch and Development Workshop, Wilmington, Delaware, 20 Sep-tember 2000.

3. J.J. Kirschbaum, “Interlaboratory Transfer of HPLC Methods: Prob-lems and Solutions,” J. Pharm. Biomed. Anal. 7 (7), 813–833 (1989).

4. P.C. Meier and R.E. Zund, Statistical Methods in Analytical Chemistry,(John Wiley & Sons, New York, NY, 1993). PT

Table I: Select acceptance criteria for assay methods per PhRMA ARDSC attendees September 2000 (2).Question ResponseDo you perform linearity upon transfer? Yes and noHow many lots for transfer? 2–3 covalidation and 1 other lot

Bracket high and low strengths,if applicable

How many repetitive analyses? 1–6 depending on percent relativestandard deviation

How many analysts 1–2, some with same analyst but at the receiving site? different equipment, day, etc.Do you spike samples for impurities? Yes and no (even split)

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