Seqens eBook - 17

CROs

similar situations in its past efforts and will have implemented means of

study design and protocol generation activity in the context of its ability

recognizing when such a situation is likely to happen, or whether it has

to relate its experience to the contracting laboratory's circumstances by

already occurred. Based on this experience, the CRO will have established

considering key questions, such as:

a means of documenting, addressing and resolving those situations.

Additionally, it is the case that best demonstrated practices in E&L are not

How much time did the CRO spend understanding the
product, the process, the circumstances and the ultimate

prescriptive and restrictive, but, rather, allow individual organizations to

objectives of the study?

operate with the flexibility inherent in "good and prudent" science. In this

situation, a CRO may have developed its own strategy and tactics around

Is the CRO offering their standard, "one size fits all" package
or does the study design and protocol reflect a customized

"good science" which may not be revealed in even the most rigorous SOP

approach tailored to fit the study's circumstances and needs?

review. Therefore, it may be useful to include a "how do you handle this
situation?" session as part of the CRO qualification. One would anticipate

Additional questions that the contracting organization should consider in

such a session focusing on issues that the contracting organization itself

evaluating the CRO's study design and study protocol are listed in Table

has experienced or heard about, and that the CRO's responses would

3. For example, the CRO's proposed extraction conditions and solvent(s)

be judged in the context of how the well the CRO's response agrees

should effectively reflect the contracting organization's study scenario

with the contracting laboratory's own solution to the issue. Another

and should contain appropriate and detailed justifications of the CRO's

important factor to consider is whether the CRO's response meets the

choices. Important aspects to consider in terms of extract analysis include

dual expectations of practicing good science and meeting regulatory

the CRO's use and justification of qualification or reporting thresholds,

compliance.

the CRO's strategy for identifying extractables and the CRO's strategy or

If one likens the process of qualifying a CRO to that of obtaining a

tactics designed to address the possibility that their screening method

driver's license, one recognizes that the qualification process that has

may leave important extractables undiscovered and unidentified.

been described to this point is much like the written portion of a driver's
license test. In theory, the written test establishes that the prospective

Table 3. Technical Qualification of Partner CROs: Important
Questions and Issues (Part D of Step 3)

driver possesses the essential knowledge to handle a vehicle in a safe
and proper manner. However, there still exists the considerable concern

A. Extracts

as to whether the prospective driver can translate and reconcile this

1. How well do the proposed extraction conditions mimic the clinical conditions
of contact?

knowledge with the practical challenges of actually operating a vehicle in
an acceptable manner. Expanding this analogy to CRO qualification, the

2. How well do the proposed extraction conditions mimic the chemical nature of the
drug product?

CRO qualification discussed up to this point has focused on evaluating the

3. How well do the proposed extraction conditions address the purpose of the study?
4. How strong is the technical justification for the extraction conditions?

CRO's ability to perform without witnessing the CRO's actual performance.

B. Extract Analysis

From the perspective of the contracting laboratory, it is useful that the
qualification stage establishes the CRO's actual ability to successfully

1. How low will they go (meaning what is their analytical evaluation threshold, AET, and
what is their justification for the AET)?

perform the critical aspects of an E&L study. While one way to accomplish

2. What is their identification strategy (and what is their justification for this strategy)?

this objective would be to give the CRO a "real" study, this approach is not

3. How do they know that they are not missing anything with their methods (that is, what
about extractables they may not have been able to detect?

without an associated risk, and it could be considered akin to giving the

4. How will they go back capture those extractables that they have missed?

prospective driver a license to operate a vehicle without taking a road test
and then hoping for the best. The short comings ofthis approach could
be mitigated if one considers the two essential aspects of an E&L study:
1.

Can an E&L study be properly designed, and can the study
design be effectively communicated in a document (such as
a protocol)?

The Competency Evaluation
By having a prospective CRO generate a mock protocol, the contracting
organization has essentially established that the CRO can think and
communicate in an appropriate and effective manner. While this is a

Can laboratory techniques be implemented so that

significant point, it leaves a major question unanswered: can the CRO

extractables can be discovered, identified and quantified?

produce output (the E&L study results) that meets the contracting

These two points suggest a means for assessing the CRO in the "heat of
battle" without actually engaging the CRO in a test. Specifically, the aspect

organization's quality requirements? Points to consider in addressing this
question include:
1.

of study design and protocol generation can be addressed by providing

CRO has performed while conducting an E&L study?

the CRO with a case situation and having it generate a study design and
protocol. Presumably this case situation would be one that the contracting

laboratory has itself experienced previously. Therefore, the performance

How well has the CRO performed the technical functions
required in an E&L study?

expectation in this case would be a safety design and protocol judged by
the contracting organization as being as good as, if not better than, their
own design and protocol in response to this situation. More objectively,
the contracting organization can judge the actions of the CRO during the
Pharmaceutical Outsourcing |

What is the technical quality of the analytical actions that the

How good are the chromatograms that the CRO generates?

How accurate and credible are the identifications and
concentration estimates provided by the CRO?

| pharmoutsourcing.com

http://www.pharmoutsourcing.com

Seqens eBook

Table of Contents for the Digital Edition of Seqens eBook

Contents
Seqens eBook - 1
Seqens eBook - Contents
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