glp sops for equipment calibration and maintenance. part 2: an organized approach to streamlining...

GLP SOPs for Equipment Calibrationand Maintenance. Part 2: AnOrganized Approach to StreamliningProcedural Documentation

Michelle Rosa and Irina Colligon*

PAREXEL Consulting, A Division of PAREXEL International 900 Chelmsford St, Lowell MA 01851, USA

Summary

As anyone who has had to deal with a Standard Operating Procedure (SOP) systemcan testify, managing these documents is a Herculean task, requiring full–timecommitment. This article proposes an alternative and more efficient approach tobuilding a manageable set of procedural/instructional documents that will help anorganization meet its scientific and regulatory needs while alleviating the strain thata gargantuan SOP system can put on its personnel.

Among the benefits of this approach are: (1) Documents are organized to followthe logical and chronological flow of the activities they describe. (2) Documents canbe located quickly. (3) Users will find what they need to know, presented in a concisemanner, without superfluous information. (4) Increased usability of the documentssince there is a logical structure to delivered information; thus, users can control thelevel of detail based on their need. (5) Reduced effort for upkeep of individualdocuments. Copyright # 2006 John Wiley & Sons, Ltd.

Key Words: Standard Operating Procedures,SOPs; Good Laboratory Practice,GLP; laboratoryequipment; process design

You must simplify. You must make thecomplex things simple. Then you mustmake it work. – I. M. Pei

Documenting Processes

In the context of a laboratory working to Good

Laboratory Practice (GLP) standards, a Stan-

dard Operating Procedure (SOP) is ‘a documen-

ted procedure which describes how to perform

tests or activities normally not specified in detail

in study plans or test guidelines’ [1]. Overall, the

above definition of an SOP is not bad, but when

taken at face value, the resulting set of SOPs

may not be optimal.

Let us consider the concept of a procedural

document, which can be defined as a document

that provides written instructions for standar-

dized performance of a specific function or

activity. This document helps ensure that study

activities are conducted and documented

*Correspondence to: I. Colligon, PAREXEL Consulting, ADivision of PAREXEL International 900 Chelmsford St,Lowell MA 01851, USA. E-mail: [email protected]

Qual Assur J 2006; 10, 203–207.Published online in Wiley InterScience

(www.interscience.wiley.com) DOI: 10.1002/qaj.378Copyright r 2006 John Wiley & Sons, Ltd.

(recorded) in compliance with the protocol/

study plan and the applicable regulatory and

organizational requirement(s) [based on 2].

When comparing these definitions, it becomes

clear that an SOP is a procedural document. It

also means that SOPs comprise but one piece of

a procedural documentation system. What other

items fall under the category of procedural

documents? On closer examination, it is not

hard to see that work practice guides (WPGs),

instructions, templates, forms, manuals, even

published literature and textbooks also describe

a standard way of performing activities, and

they too can be placed in this broad category.

Even organizational policies are procedural

documents.

So how does one reconcile the statement from

the GLP regulations ‘A testing facility shall have

standard operating procedures in writing setting

forth nonclinical laboratory study methods that

management is satisfied are adequate to insure

the quality and integrity of the data generated in

the course of a study’ [3] with the idea that all

SOPs are procedural documents, but not all

procedural documents are SOPs? Further in the

same section (authors’ underline) ‘Each labora-

tory area shall have immediately available

laboratory manuals and standard operating

procedures relative to the laboratory procedures

being performed. Published literature may be

used as a supplement to standard operating

procedures [3].’ The OECD GLP monograph

has a similar statement [1]. Clearly, these

regulations tell us that it is acceptable to

supplement SOPs with other materials.

Not all of the documents listed above carry

the same weight, Table 1 summarizes their

general positions in the procedural document

hierarchy. Inset 1 provides an in-depth descrip-

tion of the types of procedural documents listed

in the table.

Procedural Document Management

All procedural documents require some form of

review and revision. The amount and frequency

of these activities vary based upon the type of

document. A procedure level document, such as

an SOP needs at least a regularly scheduled,

relatively frequent, review, with most companies

setting the cycle at up to two years. In addition,

to remain current, an SOP should be revised

when the process or related policy, regulation or

organization is changed.

Supporting documents, even published ones,

should not be accepted blindly, but need to be

reviewed to ensure they can be followed.

Adjustments and changes should be made if

necessary. Whether these documents require

scheduled review will depend on their intended

use, with work instructions likely to benefit from

this review. Equipment manuals, once accepted,

will need to be updated and/or revised to

coincide with instrument improvements/up-

grades, including possibly even new versions of

software. A new or replacement instrument

necessitates a new manual.

It is important to remember that in the

procedural document model described here,

compliance with the processes depends not only

on the SOPs, but also on the supporting

documents and tools that they reference. This

means that the contents of these materials must

Table 1. Hierarchy of procedural documents (see Inset 1 for a detailed description of thedocuments described in this table)

Document level Document purpose Detail level

Policy Organization’s position on a topic Organizational (little detail)Procedure (SOPs) WHO/WHAT/WHEN Functional overview of a

processProcess(some detail)

Supporting Documents(WPGs, Manuals)

HOW to complete a particular task Task (step-by-step instructions)

Tools (Forms, Logbooks) Document what happened As necessary to support data

204 M Rosa and I Colligon

Copyright r 2006 John Wiley & Sons, Ltd. Qual Assur J 2006; 10, 203–207.DOI: 10.1002/qaj

be controlled, and, as documents and manuals

are revised, the obsolete versions must be

retained per the same regulatory requirements

that apply to the SOPs. It is also important to

remember that, just as with SOPs, the necessary

supporting documents must be readily available

to the instrument users. It is a good idea to store

one set of the documents within each laboratory

or at least in a location that is central to all

laboratories.

Today, more frequently than not, the term

SOP is applied to any and all documents

that provide instructions. Such broad definition

is reflected in the fact that it is not uncommon

for GLP laboratories to have several hundred

SOPs, the majority of which are dedicated to

use and maintenance of equipment. Upon

closer examination, many of these SOPs are, in

effect, retyped manuals. One important issue

that drives this trend is the enforcement

power of different procedural documents. In

simple terms, an SOP describes what manage-

ment or regulations state MUST be done. On the

other hand, the manual shows how to do

something, without any management-endorsed

and enforceable provisions. It is this apparent

lack of ‘judicial’ power that drives the need to

retype the manuals into SOP format. But is the

manual that powerless?

Consider if an SOP, without actually quoting

the manual, simply states that when performing

a task, the operator must follow the manual. By

this simple statement, we have achieved the

following:

* Extended the power of an SOP to the manual,

because by not following the manual, the

operator will violate the SOP.* Shortened the SOP.* Avoided retyping the manual.

Taking the newfound efficiency one step

further, consider now the case of automatic

precision pipettors. Most modern laboratories

have quite a number of these, usually from

multiple manufacturers and designed to deliver

varying volumes. The need to follow a manual

does not change based on model, only the

instructions do. This means that a single

statement, such as ‘All automatic precision-

pipettors must be used according to their

respective manuals’ potentially eliminates the

need for a substantial number of SOPs. This

‘trick’ may be applied to other equipment types

Inset 1. Procedural Document Types

Organizational level policy documents define the ‘Why’ aspect of the activities and their constraints. Documents inthis category should outline the organization’s key policies including the official interpretation and application ofpertinent regulations. At this level, there are usually no specific processes or procedures associated with complyingwith the policies. For example, a policy may state that all employees will comply with applicable regulations. It is notnecessary, however, to describe how they will go about complying. These documents serve as guidances fordescribing the ‘How’ in the lower level procedural documents. Detailed discussion of the policy documents is outsidethe scope of this series. It is important to note, however, that in addition to these policies, there are policies thatdefine parameters of certain activities, and these are usually included in the SOPs dedicated to these activities.

Procedure level documents should give a functional overview of an activity, using a moderate amount of detail. Atthe top of this group are the SOPs; and their purpose is not only to outline the standard process and its constraints(‘How’), but also to describe the responsibilities (the ‘Who’) as well as the timeframe (the ‘When’) for performing theactivity. At this level, it is relatively easy to keep the information in the documents generic, because they are notmeant to convey a high level of detail. This helps keep down maintenance of the documents, as they will not requirean update for minor changes, as they often do. An example of such a document would be an SOP on the use and careof precision balances.

Supporting documents are meant to supplement the general descriptions contained in the SOPs, providing important‘How’ details while executing a particular activity or task. Instruction manuals, method documents, and workinstructions/work practice guides (WI/WPG) are examples of supporting documents.

Tools are items that help users along the way. Checklists, notebooks, data collection forms, and templates areexamples of tools.

GLP SOPs for Equipment Calibration and Maintenance 205


and groups; however, the emerging concern is

not to make the SOPs too generic and too few.

Taking a Process Inventory

To create a well-balanced set of procedural

documents, one that provides appropriate in-

formation in a logical and efficient manner, it is

important to get a clear understanding of what

actually requires documenting, be it in the form

of an SOP, or another procedural document. Just

as good science requires planning an experiment

before performing it, in building a procedural

document set, it is best to start with creating an

inventory of required materials – a process

inventory. A process inventory is simply a list

of all critical activities/topics that require

documentation. Within the list, the processes

and activities are grouped into functional

categories.

When developing a process inventory, con-

sider which activities are regulated or essential

to an organization’s ability to perform its core

business mission. For the purposes of this series,

we will only consider processes and procedures

that apply to use and management of equip-

ment, although the concept can be extrapolated

to apply to any facet of the pharmaceutical

industry and beyond.

Creating a Procedural DocumentationSystem

Once a process inventory is complete, the next

step is to determine how to effectively document

each piece of the inventory. For each process/

topic on the list, start by considering the

following questions:

* Are there special circumstances or policies

related to this instrument, systems, or group

of instruments that need to be stated?* How critical is this instrument?* Is an instrument under consideration used by

itself (e.g. pipettors) or as part of a system

(e.g. mass spectrometric detector in an LC/

MS system)?* If there is no manual, or it is not up to par,

what needs to be done to make it useful?

Inset 2 provides an example of the instrumen-

tation portion of the SOP list for a bioanalytical

laboratory.

As described earlier in this article, if following

a manual is required, then the manual is part of

supporting documentation to the SOP, allowing

the SOP to be short and concise. There may be

circumstances where the manual will only be

partially followed, a manual is not available or it

does not contain precise-enough detail to

describe a process. In most such cases, the

manual can be created or updated to reflect the

additional information. In some cases, it may

also be necessary to develop an instrument-

specific SOP.

Examining the titles of equipment SOPs in a

laboratory, it is not unusual to see separate

documents describing, respectively, use, calibra-

tion and maintenance of an instrument. In the

spirit of keeping the length of each document to

a minimum, it may be wise to split them in this

way. On the other hand, if a manual is being

used to describe the bulk of these activities, the

content of the SOPs will be limited, and may as

well be combined into a single document.

A similar approach may be considered for

Inset 2. Process inventory example – equip-ment SOP topics for a bioanalytical chroma-tography laboratory

Analytical and Computer Instrumentation/GeneralSpecimen Preparation EquipmentAnalytical Systems

Care and Maintenance of Chromatographic SystemsCare and Maintenance of LC/MS Systems

Precision Measuring DevicesCare and Maintenance of BalancesCare and Maintenance of Pipettors and Diluters

Computerized SystemsComputerized Systems/General Procedures (specifics

are outside the scope of this series)Miscellaneous Equipment

Care and Maintenance of Freezers and RefrigeratorsCare and Maintenance of Barcode Readers

206 M Rosa and I Colligon


ensuring SOP coverage for instruments classified

as non-critical, or when the processes documen-

ted in the SOPs are relatively straightforward.

However, for instruments, and particularly

instrument systems, that are considered critical,

or have very detailed processes, it may be best to

maintain separate SOPs. The range of possible

situations is broad, so this is a decision that is

best made on a case-by-case basis.

Conclusion

In summary, a rational approach to streamlining

procedural documentation will benefit equip-

ment-users and simplify compliance-related ac-

tivities. Achieving such a documentation system

nevertheless represents a considerable challenge,

and a future installment in this series will

endeavor to provide additional guidance on

how to achieve the necessary balance within

the document hierarchy.

References

1. OECD Series on Principles of Good Laboratory

Practice and Compliance Monitoring Number 1.

OECD Principles of Good Laboratory Practice. Orga-

nisation for Economic Co-operation and Develop-

ment, ENV/MC/CHEM(98)17, Paris 1998.

2. International Conference on Harmonisation Guide-

line on Good Clinical Practice, 1996.

3. U.S. Food, Drug Administration, Title 21 Federal Code

of Regulations Part 58, Good Laboratory Practice for

Nonclinical Laboratory Studies.

GLP SOPs for Equipment Calibration and Maintenance 207
