glp sops for equipment calibration and maintenance. part 1: an overview

DOI: 10.1002/qaj.369

GLP SOPs for Equipment Calibrationand Maintenance. Part 1:An Overview

Michelle Rosa*

PAREXEL Consulting, a Division of PAREXEL International 1400 N. Providence Rd, Suite 1050, Media, PA

19063, USA

Summary

Writing Standard Operating Procedures (SOPs) for laboratory equipment is viewed asa necessary evil. As a result, many of these documents are not practical or useful to areader. Writing these documents does not have to be so frustrating. With fore-thought, careful planning and collaboration, laboratory SOPs can be practical anduser-friendly documents that support continued compliance and create a platformfor future growth. Copyright # 2006 John Wiley & Sons, Ltd.

Key Words: Standard Operating Procedures; SOPs; Good Laboratory Practice; GLP; laboratory

equipment; process design

Writing Standard Operating Procedures (SOPs)

can be a daunting process. Virtually all facets of

the drug development process require procedur-

al documentation in some shape or form. Reg-

ulatory authorities expect to see SOPs for

activities ranging from pre-clinical studies to

the manufacturing process and throughout clin-

ical development.

Good Laboratory Practice (GLP) is the regu-

lation that governs pharmaceutical research,

requiring that pre-clinical studies in support of

marketing applications be conducted in accord-

ance with its provisions. It has also become an

industry standard that bioanalytical work for

clinical studies is performed under GLP. Possibly

because of their age, the GLP regulations are

quite vague on the subject of analytical labora-

tory equipment used for the GLP work, leaving

plenty of room for interpretation. The ambiguity

makes it difficult to definitively identify which

processes within the laboratory fall under the

GLP umbrella, and creates unique challenges for

SOP development in analytical laboratories per-

forming GLP work.

In the US Food and Drug Administration

(FDA) GLP regulation, 21 Code of Federal Reg-

ulations (CFR) Part 58 [1], Section 58.63 states:

‘The written standard operating procedures

required under Section 58.81(b)(11) shall set

forth in sufficient detail the methods, materials,

and schedules to be used in the routine inspec-

tion, cleaning, maintenance, testing, calibration,

and/or standardization of equipment, and shall

specify, when appropriate, remedial action to be

taken in the event of failure or malfunction of

equipment. The written standard operating pro-

cedures shall designate the person responsible

for the performance of each operation.’

The Organisation for Economic Co-opera-

tion and Development (OECD) Monograph

1, Principles of Good Laboratory Practice

*Correspondence to: M. Rosa, PAREXEL Consulting,a Division of PAREXEL International 1400 N. ProvidenceRd, Suite 1050, Media, PA 19063, USA. E-mail:[email protected]

Copyright r 2006 John Wiley & Sons, Ltd. Qual Assur J 2006; 10, 107–110.

[2, Section 7.4], echoes the sentiment, requiring

that SOPs should be available for the use, main-

tenance, cleaning and calibration of laboratory

equipment.

Writing a document simply because regula-

tions say so is not difficult. The challenge is to

create a user-friendly SOP that continuously

ensures standards for quality and validity of

data per regulatory requirements and provides

value to its readers.

This article is the first installment in a series

that will endeavor to help readers create such

documents, beginning with an overview of key

points to help ensure that time and effort spent

on the development of SOPs are not wasted.

Subsequent installments will discuss the key

points in further detail. It should also be noted

that while laboratory equipment is the major

focus of the discussions, most of the concepts

presented are also applicable to the development

of SOPs for other areas.

Ten Tips for Writing SOPs forEquipment Calibration andMaintenance

For the purpose of this series, equipment is

broadly defined as any instrument used in

the generation, measurement, or assessment of

data.

Tip 1: Decide if an SOP is Necessary

Just because an instrument resides in the labo-

ratory and is used for GLP work, does not mean

it needs ‘its own’ SOP. Begin by creating a com-

prehensive list of the documents you think you

will need. A good rule of thumb in determining

the need for an equipment SOP is to start by

assessing the importance of the instrument to the

data and the risk of its malfunction on the

validity of data. The determination should be

based not only on the type of equipment, but

also on its use. For example, a freezer used to

store labile materials requires an SOP describing

its calibration, but an icemaker does not require

special consideration.

Tip 2: Choose an Appropriate Author

When selecting an SOP author, it is important to

choose someone who possesses good writing

skills and is familiar with SOPs, though not

necessarily an expert equipment user. The mis-

take often made is to choose an author based

exclusively on his or her writing abilities, e.g., a

professional SOP writer, with no consideration

given to his/her experience with the topic to be

described; or an expert on the subject at hand,

e.g., a ‘super user,’ with questionable writing

skills. To ensure that the document conveys the

necessary information in a readable manner, it

may be best to balance the skills by taking the

cooperative route and having the user and writer

jointly create the document.

Tip 3: Follow the SOP on SOPs and theSOP Template

Every organization should have an SOP on SOPs

– a document that describes how the life cycle of

the SOPs is managed from their inception

through retirement and how the SOPs are used.

When writing an SOP, ensure that it follows the

policies and format outlined in the SOP on

SOPs. A typical SOP includes at least the fol-

lowing sections: Purpose, Scope, Responsibili-

ties, Equipment and Materials, and Procedure. It

is good practice to include a reference section

that lists related documents, manuals and appli-

cable regulatory references. When listing

responsibilities associated with the process, it is

more practical to use functional titles rather

than personnel names and even job titles, as

these may change faster than an SOP can be

updated.

Tip 4: Consider Mapping the ProcessFirst

When documenting a process, it is useful to start

by visualizing it in the form of a map. A process

map need not be complex, contain excessive

detail, or be verbose. Use of the ‘Supplier,

Input, Process, Output and Customer’ (SIPOC)

108 M Rosa


approach, as described in the Six Sigma meth-

odology, serves this purpose very well.

Tip 5: Seek Input from Others

Do not write an SOP in a vacuum. Consulting

others during this process is crucial to ensuring

the SOP is usable. Seek input from current

equipment users, management stakeholders, and

training developers to ensure a well-rounded

process. Quality Assurance (QA) personnel can

provide valuable insight into the latest regula-

tory thinking and requirements. For any SOP

that covers a component of a bigger process, do

not overlook the inter-relationship between

the subject at hand and the rest of the process.

And last, but not least, ‘test-drive’ the SOP

on non-expert users. This provides an

opportunity to identify missing or unclear

information.

Tip 6: Be Aware of RegulatoryRequirements and Industry Best Practice

Most of the regulations that govern how work

is done are reactive; they were created in an

effort to prevent recurrence of past lapses.

Responses to regulatory requirements differ;

some organizations take more elegant or more

effective routes than others, thus raising the bar

of the expected performance for everyone. On

occasion, the expectation turns into requirement

and it is thus in the interest of every organization

to build the emerging best practices into their

documented processes.

Tip 7: Do not Retype – Leverage!

Having an SOP that is simply a retyped copy of

a user manual, a section of a user manual, or

even a publication provides no value to a user.

From the regulatory standpoint, it is perfectly

acceptable to simply reference these materials in

the SOP. The OECD Principles of Good Labo-

ratory Practice, Monograph 1 [2], clearly state,

‘Published text books, analytical methods, arti-

cles and manuals may be used as supplements to

these Standard Operating Procedures.’ If a

procedure consists of performing a process as

outlined elsewhere, such as in a user manual,

simply refer to it in the SOP. One benefit of ref-

erencing manuals is that the number and volume

of the SOPs is much lower. For example, only

one SOP may be required to describe the oper-

ation of multiple volume pipettors, if the users

are directed to follow the model-specific manu-

als for routine operation. Furthermore, addition

or deletion of individual models will not trigger

SOP revisions.

Tip 8: Remember: SOP and Protocol arenot the Same

An SOP is a document that outlines a standard

project - or study-independent process. A pro-

tocol, on the other hand, is a study-specific doc-

ument that describes how a process is carried

out within a single study. If a study has special

requirements for maintenance or calibration of

equipment, these should be described in the

protocol. The protocol may take precedence

over the SOP; however, this should be clearly

documented. More importantly, this route

should not be overused. On occasion, to accom-

modate a process change that is applicable to a

long-term project, it may be necessary to create

a project-specific SOP. This too should be clearly

documented and reserved for special cases.

Tip 9: Identify the Target Audience

Be sure to consider who will ultimately use the

SOP. Regulatory authorities and corporate man-

agement may read the SOP, but it is ultimately

the end-user of the equipment that will have to

follow it. For this reason, it is acceptable to use

technical terminology as necessary for the usa-

bility of the SOP. Be cognizant, however, that

not all readers have the same level of subject

matter knowledge, and make a reasonable effort

to accommodate the difference. Use of labora-

tory equipment requires a relatively high level of

technical knowledge, so in accommodating po-

tential readers, aim for the properly educated

reviewer who may not be an expert in the par-

ticular subject.

GLP SOPs for Equipment Calibration and Maintenance 109


Tip 10: Consider How Much Detail isNecessary

For a user to perform tasks accurately, a fair

amount of detail around the procedure is nec-

essary. Excessive details, however, can over-

whelm the reader, and place undue restrictions

on activities. Poor synchronization between the

SOP and the process is a classic example of

noncompliance. For example, names of reagent

manufacturers can be easily omitted from an

SOP without jeopardizing compliance.

Closing Remarks

Tedious, laborious, excruciating, agonizing and

frustrating are the terms that first spring to mind

at the mention of writing SOPs for laboratory

equipment. Useless, worthless and ineffectual

are words often used to describe these SOPs. In

reality, the labor should not be so painful and

positive attributes such as practical, valuable,

functional and informative should be used to

describe its fruit.

Acknowledgments

Special thanks to Irina Colligon for her

assistance and support with this manuscript.

References

1. US Food and Drug Administration. Title 21 Federal

Code of Regulations Part 58. Good Laboratory Prac-

tice for Nonclinical Laboratory Studies (as revised in

April 2005).

2. Organisation for Economic Co-operation and Devel-

opment Series on Principles of Good Laboratory Prac-

tice and Compliance Monitoring. Monograph No. 1

OECD Principles of Good Laboratory Practice (as

revised in 1997).

110 M Rosa


glp sops for equipment calibration and maintenance. part 1: an overview

Documents