Seqens eBook - 8

Top Mistakes in Analytical
Method Validation and
How to Avoid Them
Ed Price, CEO, Seqens CDMO North America
Method validation is essential in proving the quality, reliability and

cutter approach that often is found to be inadequate since it doesn't take

consistency of a chemical being developed. Proper validation of a

into consideration the uniqueness of each New Chemical Entity (NCE)

method provides documented evidence of method performance and

or Active Pharmaceutical Ingredient (API) being developed. In fact, the

prescribes ongoing measures to ensure quality monitoring for the life

majority of negative audit findings fall into three main categories:

of the method. It is essentially the blueprint for future manufacturing of
the chemical. Yet, inadequate method validation persists as a significant

*

The use of non-validated methods for critical decision making

problem in pharmaceutical development and manufacturing. When not

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Inadequate method validation that does not provide the

performed properly, it can result in delays in product approval, require

necessary information

a complete doover of API development, or cause regulatory delays in

*

commercialization. But, being aware of common mistakes, and how to

Method validation that lacks appropriate controls to maintain the
integrity of the validation

avoid them, will help ensure analytical methods are successfully validated,
leading to successful commercialization.

The consequences of negative audit findings are numerous for both a

What the FDA Wants

sponsor and a CMO in terms of cost and commercialization potential.

Generally speaking, the FDA requires method validation data that

product, incomplete method validation can impact stability studies that

supports and documents the identity, strength, quality, purity, and

don't meet specification. In addition the proven efficacy of the drug or

potency of drug substances and drug products, which must be

even its safety profile can be compromised.

In addition to potential delays in starting clinical trials or shipping the

reproducible time and again.

Typical Culprits in Method
Validation Problems

The FDA provides clear guidance on method validation requirements,
which is closely aligned to the International Conference on Harmonisation
(ICH) guidance. According to the guidance, early in the development of
new analytical procedures, the choice of analytical instrumentation and

Method validation problems can be found even before validation studies

methodology should be selected based on the intended purpose and

begin, and the root cause is a lack of thorough understanding of the

scope of the analytical method. Parameters that may be evaluated during

physiochemical properties of the molecule, which should be determined

method development are specificity, linearity, limits of detection (LOD)

at the start of the project. These include ascertaining the molecule's

and limits of quantitation (LOQ), range, accuracy, and precision.

solubility, pH, pKA, reactivity, melting point, boiling point, moisture

During early stages of method development, the robustness of methods

sensitivity, light sensitivity and other characteristics.

should be evaluated to help Contract Manufacturing Organizations (CMOs)

Only when the physiochemical nature of the compound is firmly

and other scientists, decide which method will be submitted for approval.

established can the appropriate validation studies be designed. For

Analytical procedures in the early stages of development are initially

example, if it is known that a material is light sensitive or moisture

developed based on a combination of a mechanistic understanding of

sensitive, then it is clearly understood that during validation studies it

the basic methodology and prior experience.

should not be exposed to light, heat or air. That type of information must

Top Mistakes Found in Review

be captured for an appropriate method validation plan.

Although these guidelines are comprehensive, following them can be

But aside from improper assessment of the physiochemical properties,

challenging, especially when drug developers attempt to use a cookie

there are three common mistakes that occur in method development:

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Seqens eBook

Table of Contents for the Digital Edition of Seqens eBook

Contents
Seqens eBook - 1
Seqens eBook - Contents
Seqens eBook - 3
Seqens eBook - 4
Seqens eBook - 5
Seqens eBook - 6
Seqens eBook - 7
Seqens eBook - 8
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