VOL. 27 NO. 1 (2015)QUALITY MATTERS

Modernisation of thespectroscopic General
Chapters in the United States
Pharmacopeia (USP)
C. Burgessa and J.P. Hammondb
Burgess Analytical Consultancy Limited, ‘Rose Rae’, The Lendings, Startforth, Barnard Castle, Co. Durham, DL12 9AB,UKb
Starna Scientific Ltd, 52–54 Fowler Road, Hainault Business Park, Hainault, Essex, IG6 3UT, UKaAs part of the USP–NF modernisation process, the General Chapters(Chemical Analysis) Expert Committee
has and continues to review collections of chapters in a holistic approachin order to align concepts and contentto ensure consistency.1 These revisions are intended to ensure that thescientific expectations defined in thechapters are aligned with current bestpractices to ensure suitability for use
when the appropriate measurements
are executed. To these ends, generalchapters currently are grouped into
two parts: <1000 chapters (i.e., thosenumbered below 1000), where thefocus, as stated in the General Notices,
is on content that may be required ifcalled for in a monograph, and >1000
chapters (i.e., those numbered 1000–1999), where these chapters give information, definition or description.
The purpose of spectroscopic General
Chapters is to provide the basis forestablishing that an instrument orsystem is “suitable for use” in a USP
monograph. This “suitability for use” isusually related to the technical performance specification of the instrument
or system and represents a minimum
standard. However, on its own, compliance to specification cannot provide
overall “suitability for use” and bestpractice guidance provides the holistic
component.
26 SPECTROSCOPYEUROPE

Hence “suitability for use” has two
distinct aspects:■■ Compliance with technical performance characteristics on the instrument/system itself,■■ Operational best practices for an
instrument/system when employedas part of a procedure stated in amonograph.
The instrument/system require ments currently described in General
Chapter <851>, Spectrophotometry
and Light Scattering, covered many
spectroscopic techniques and hadremained essentially unchanged overmany years. Therefore, in the USP
Review Cycle 2010 to 2015, it wasdecided to generate specific pairsof chapters for each of the main
spectroscopic types. The below 1000
chapters would define minimum
standards for compliance for use in amonograph, the paired above 1000chapter would give theory, guidance
and recommendations for best analytical practices. In general, below 1000
chapters include procedures, instrument qualification and validation/verification sections. Each section involves
an assessment of method-specificrequirements to ensure the suitabilityof the system and related measurements. General Chapter <851>, itself
would be deleted after all the newchapters were approved.

However, it should be noted that
this holistic approach has already been
applied to two other spectroscopic chapters, currently in USP 37 2014, Nuclear
Magnetic Resonance Spectroscopy<761> and its paired best practices
chapter Applications of Nuclear Magnetic
Resonance Spectroscopy <1761> andMass Spectrometry <736> and its paired
best practices chapter Applications ofMass Spectrometry <1736>.
The objective was to articulate thebasic elements required before andduring the execution of a spectroscopic
measurement to ensure that suitability for use has been confirmed. As an
example, the validation/verification
requirements for spectroscopic methods are specific for the procedures in thechapters.
Many of these concepts are not newto USP. The changes to the spectroscopy chapters are consistent with thosedefined in Chromatography <621>;
that is, the user must demonstratethat the system is “suitable for use”.
It is important that before executionof a measurement the analyst should
demonstrate method-specific suitability
for the instrument to ensure the integrityof the measurement.
The proposed new below 1000 chapters have a common structure irrespective of the spectroscopic technique
namely:www.spectroscopyeurope.com

QUALITY MATTERS■■ A short introduction to the particular technique and a link to the associated best practices chapter above
1000,■■ Qualification requirements for IQ &OQ with recommended procedures
and the link to Analytical Instrument
Qualification General Chapter<1058>,■■ Specific critical attributes of analytical procedures involving the particular technique,■■ Validation and verification needs
as required by General Chapters<1225> and <1226> for alternative
methods being developed for pharmacopeial monographs.

Analytical instrument
qualification (AIQ)
Analytical Instrument Qualification<1058> provides a risk-based frameworkfor generating documented evidence
over the lifecycle that the instrument orsystem is, and remains suitable for usein a monograph. <1058> is currently
in revision with the intent of extending
it to be compatible with GAMP 52 and
GAMP Laboratory Good Practice Guide
2nd Edition.3 An article outlining proposals
for change has been published.4 In addition, the extension proposal has beenpublished.5
AIQ is currently defined as the collection of documented evidence that aninstrument performs suitably for itsintended purpose. Use of a qualified
instrument in analyses contributes toconfidence in the validity of generated
data. Chapter <1058> further characterises the steps in instrument qualification
during AIQ:■■ Design Qualification (DQ): The
documented collection of activities
that define the functional and operational specifications of the instrument and criteria for vendor selection
based on the instrument’s intended
purpose.
■■ Installation Qualification (IQ): The
documented collection of activities
necessary to establish that an instrument is delivered as designed andspecified, that it is properly installed
www.spectroscopyeurope.com

in the selected environment and that
this environment is suitable for theinstrument.
■■ Operational Qualification (OQ):
The documented collection of activities necessary to demonstrate thatan instrument will function according to its operational specificationin the selected environment. The
extent of OQ testing that an instrument undergoes depends on its
intended applications. Therefore,no specific OQ tests for any instrument or application are offered in<1058>. It should be noted thatroutine analytical tests do not constitute OQ testing.
■■ Performance Qualification (PQ):
The documented collection ofactivities necessary to demonstrate that an instrument consistently performs according to thespecifications defined by the userand is appropriate for the intended
use. PQ tests may resemble those
performed during OQ, but the specifications for their results may be set
differently if required. Proceduresfor OQ and PQ testing that comply
with regulatory expectations are
not well defined and are subject todifferent interpretations.
The qualification tests and acceptance criteria are included in thebelow 1000 chapters to establish
minimum pharmacopeial require ments for instrument performance.
Ultimately, the use of a qualified
instrument contributes to confidence
in the validity of analytical data used
to guarantee patient safety. The chapters will stipulate that manufacturerrecommended OQ and PQ tests andacceptance criteria may be used if
deemed scientifically equivalent. Thiswill prevent the AIQ tests in the <1000
chapters from becoming excessively
prescriptive.

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VOL. 27 NO. 1 (2015)QUALITY MATTERS<1226>, are currently under review anda Stimuli article has been published.6

Revision of General
Chapter <851>

Figure 1. Revision Paths for Spectroscopic General Chapters.

is covered under both the ICH guidelines and Validation of CompendialProcedures <1225> even though thepredominant theme for each of these
documents historically has been validation of chromatographic procedures.
The objective of the current modernisation effort is to include validation
sections in the various spectroscopy
28 SPECTROSCOPYEUROPE

chapters thus providing both general
direction for the validation of procedures based on these methods andspecific validation requirements thatare important for specific spectroscopic
approaches.
It should be noted that all three
general chapters related to validationand verification, <1224>, <1225> andAs noted earlier, the current GeneralC h a p te r < 851 > c o v e r s m u l t i p l espec troscopic t ypes, and has notbeen subjec t to a major revision
for many years. Whilst the general
spectroscopic principles detailed in
the current <851> describe the fundamental requirements, it was felt thatthey are too vague to meet the extensive and increasing use of instrumental spectroscopic techniques, and theassociated current (and future) regulatory requirements. In addition theproliferation of the application of newspectroscopic techniques makes revision of the current <851> essential.
The following new spectroscopic chapter pairs have been developed in accordance with the approaches outlined
previously:■■ Atomic Absorption Spectroscopy,<852> & <1852>■■ Fluorescence Spectroscopy, <853>& <1853>■■ Mid-Infrared Spectroscopy, <854> &<1854>■■ Turbidimetry and Nephelometry,<855>■■ Near Infrared (NIR) Spectroscopy,<856> and <1856>■■ Ultraviolet-Visible Spectroscopy,<857> & <1857>■■ Raman Spectroscopy, <858> &<1858>
These together with otherspectroscopic chapters are shownin relationship to the current <851>
in Figure 1, “Revision Paths forSpectroscopy General Chapters”. Notethat neither NIR nor Raman spectroscopies are adequately covered in <851>
and had previously only above 1000
information chapters. This situation has
now been rationalised.

Revision history during the2010–2015 cycle
The drafts and revisions for theseSpectroscopy General Chapters werewww.spectroscopyeurope.com

VOL. 27 NO. 1 (2015)QUALITY MATTERS
published in Pharmacoeial Forum(PF) from 2011 to 2015. This is available from the USP website and is free.
Back issues are also available. The USP
standards are public standards andinterested parties are requested tocomment. We encourage everyone to
subscribe and give input to this important process. All comments are madeavailable to the Expert Committee forconsideration and review. The journey
to a final new or revised standard is
carefully procedurally controlled andhas to gain approval of the Councilof Experts before it is made official.
A synopsis of this process is given
below.
■■ After extensive drafting and review
at the start of the cycle, the six
initial chapters: Atomic Absorption
Spectroscopy, <852> and <1852>,
Mid-Infrared Spectroscopy, <854>
and <1854> and Ultraviolet-Visible
Spectroscopy, <857> and <1857>
were published in late 2011, inPF 37(5).
■■ Following the comment period, theonly chapter which did not require
substantial revision was <1857>,
the Ultraviolet-Visible Spectroscopy
general information chapter.
■■ In early 2013, the t wo new
Fluorescence chapters, namely<853> and <1853> were published
in PF 39(1). The five, reviewed andrevised, remaining chapters fromthe initial publication set wereagain submitted for comment inPF 39(2). The “remains” of <851>
was renamed “Light Scattering” andpublished in PF 39(3).
■■ Once again, significant comments
were received and reviewed and inearly 2014, these five chapters, i.e.
<852>, <854>, <857>, <1852>
and <1854>, together with thereviewed Fluorescence Spectroscopy,<853> & <1853>, were published
in PF 40(1).
■■ Having now disseminated <851>
into the appropriate techniquespecific chapters, some techniques
were not covered. Nephelometry,
Turbidimetry and Visual Comparison
were assigned to a new <855>

www.spectroscopyeurope.com

chapter, which was published at theend of 2014, in PF 40(6).
■■ Also in PF 40(6) are the rationalised
and revised Raman chapters <858>
and <1858>, derived from the existing <1120> which were open forcomment until 31 January 2015.
■■ In PF 41(1) 2015 the rationalised andrevised NIR chapters <856> and<1856>, derived from the existing<1119>, were published and openfor comment until 31 March 2015.
■■ Therefore, the following chaptersbecome official in USP 38 (1 May2015):■■ Atomic Absorption Spectroscopy,<852> & <1852>■■ Fluorescence Spec troscopy,<853> & <1853>■■ Mid-Infrared Spec troscopy,<854> & <1854>■■ Ultraviolet-Visible Spectroscopy,<857> & <1857>■■ However, monographs will still reference <851>. In other words thechapters will be official but their use
is not mandatory because they are
not referenced in any monograph.
This will provide one year of transition.
In USP 39 (1 May 2016) all the references to <851> will be eliminated andreplaced by the appropriate new chapters. This is when the chapters became
fully applicable.

From a spectroscopic viewpoint, thenew Chemometrics Chapter will bevery important. In addition CD/ORD,
XRF and XRD may be included in thecycle. At present there are no definite
plans for a companion chapter <1855>
for <855> Nephelometry, Turbidimetry
and Visual Comparison, although it may
well happen especially as there is growing interest in these techniques from abioanalytical perspective. In addition
there is likely to be a revision of Analytical
Instrument Qualification General Chapter<1058>.
We hope that practicing
spectroscopists will make the timeand ef for t to keep in touch withthese developments and comment.
Over the years we have heard many
practitioners complaining about theappropriateness of monographs andGeneral Chapters. You now have thechance to assist with the change
process. We strongly encourage you
to use it!

References
1.

2.

3.

The future (2015–2020cycle)
In addition to the publication of therevised NIR and Raman chapters,
the associated suppor tive scienceof Chemometrics is undergoing anextensive review, as are the fundamental concepts of Validation andVerification.
So again, the next cycle is going to
be an exciting challenge. We do not
yet know who will be involved in thenext cycle, because the new Councilof Experts will not be elected until
April 2015 and the resultant Expert
Committees will be appointed shortly
after that. The new cycle begins officiallyin July 2015.

4.

5.

6.

“An alignment of concepts and content
across the spectroscopy general chaptersin the United States Pharmacopeia-NationalFormulary”, Pharmacopeial Forum 40(1)(Jan.–Feb. 2014).
GAMP © 5: Risk-Based Approach toCompliant GxP Computerized Systems.
International Society for PharmaceuticalEngineering (ISPE), 5th Edition (February2008). http://bit.ly/16ydr1t
GAMP© Good Practice Guide: Risk-BasedApproach to GxP Compliant LaboratoryComputerized Systems. International Society
for Pharmaceutical Engineering (ISPE), 2ndEdition (October 2012).
C. Burgess and R.D. McDowall, “Focus onquality; an integrated risk assessment foranalytical instruments and computerizedsystems”, Spectroscopy 28(11), 20–27(2013).
L. Vuolo-Schuessler, M.E. Newton, P. Smith,
C. Burgess and R.D. McDowall, “Harmonizing
USP <1058> and GAMP for analyticalinstrument qualification”, PharmaceuticalEngineering 34(1), 1–8 (2014). http://
www.ispe.org/pharmaceutical_engineering/
january2014“Lifecycle management of analytical procedures: method development, procedureperformance qualification, and procedure
performance verification”, Pharmacopoeial
Forum 39(5) (2013). http://www.usp.
org/usp-nf/notices/stimuli-article-lifecyclemanagement-analytical-procedures-postedcomment

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