Writing SOPs

Writing SOPs

Dr. Ammar Raza

Clinician, Clinical Affairs Manager & Teacher

Basic Principle in CR…..

Write down what you do, do what is written down!

What we will discuss today… Background What is an SOP? Why an SOP?

Importance of SOPs What should an SOP contain? Writing SOPs: Intro Writing SOPs: General Tips How to write a SOP?

Stopping Problem!! Who writes an SOP?

What format should be used? Before & After Writing……. What should SOP cover?

Step-by-step Approach

Background

Performing CTs is a complicated business Bound by regulations & GCP, with the

overriding concern of protecting safety and welfare of study subjects

Sites must follow each protocol exactly & meet other sponsor demands

Best way to ensure that all these conditions are met is formulate and follow standard operating

procedures (SOPs)

What is an SOP?

An ESSENTIAL Document The who, what, when, how, and why of

clinical research operations Ensures consistency, compliance, and

accountability of personnel Organizations without clinic-specific SOPs

run a high risk of GCP non-compliance and poor productivity

What is an SOP?

Critical tools in successful business operations for all those involved in doing CTs, investigative sites sponsors IRBs SOPs are critical to compliance and high

performance standards

What is an SOP?

ICH-GCP guidelines defines SOPs“Detailed, written instructions to achieve

uniformity of performance of a specific function”

Just that …..The “procedures” & processes that you use and “operate” under that have been “standardized” to ensure that

you do them the same way each time

Why SOPs?

Performing CR is a COMPLICATED business It is bound by regulations and GCP

overriding concern of protecting safety and welfare of study subjects

Sites must follow each protocol exactly + meet other sponsor demands

Best ways- formulate and follow SOPs They are essential for standardizing processes, for

ensuring regulatory & organizational policy requirements r met for training new personnel for managing workload

Why SOPs?

Because study protocol is usually a brief document…… it can give details of how each procedure is to be done, who will do it etc.

Provide a historical record of steps in the how, why and when

Serve as a training tool for teaching users

Importance of SOPs

Every good quality system is based on its Standard Operating Procedures (SOPs)

SOPs are necessary for a clinical research organization pharmaceutical company a sponsor a contract research organization an investigator site an ethics Committee or any other party involved in CR

To achieve maximum safety and efficiency of the performed TASKS

Importance of SOPs

Audits have shown sponsor/CRO files are missing important info

in several areas with respect to sponsor/CRO training no monitor CVs (75% of 226 sites) no evidence of training in SOPs (57%) No evidence of training in the therapeutic area

(53%) no evidence of training in GCP (36%) and no evidence of adequate experience

Importance of SOPs

During of selection of CROs First thing done

Look for SOPs quality of SOPs compliance with SOPs other QA systems (e.g. internal auditing,

proficiency testing), determine exactly which SOPs (i.e. sponsor or

CRO) will be used

What should an SOP contain?

Two parts 1st part: Outline or summary – includes

description of the aim or purpose scope when it should be reviewed and known risks associated with the task in

question

Contd…

What should an SOP contain?

2nd part Accurate step-by-step description of how the

task will be carried out Who is responsible for each step

Writing SOPs: Intro

Writing SOPs is not an easy process Very time-consuming Involves analysis of

your processes pays big dividends

when complete

Writing SOPs: General Tips

A formal document -describes procedures that will be followed to accomplish various tasks

Style of the text should be clear, concise, brief and specific to the subject

Should be written to provide instructions for completion of certain procedures Mustn’t be ambiguous or confusing

Statements concerning procedures to be followed should be made categorical use of words - 'must' and 'will'

e.g. 'the following procedure must/will be performed'


Important to use words - “will” or “shall” to describe procedural steps

Best to avoid words such as “should,” “could,” and “may.” Why?

These words convey a since of option SOPs are not optional


The word 'may' is to be used only when the conditions are stated e.g. 'the investigator may enter a patient into

the study without patient consent only in an emergency and when the patient is unconscious'

How to write?

Stopping problem!!

Most writers - no problem getting started Sometimes follow thro’ needs more info

Most difficult thing for most –”to stop”

•Start at the beginning •Follow the task through to the end•Then stop

Sounds easy

Avoid long, complex sentences & paragraphs- make SOP difficult to follow

Avoid Stopping problem!!

Begin by identifying the purpose of your SOP’s

1. will help to focus your energy 2. set limitations on the necessary content

Create an outline of what is actually done on a day-to-day basis

Develop the skeleton i.e. the structure of the SOPs important to design your SOPs to achieve

specific results

Designing

Some design options: Simple steps Hierarchical steps Graphic procedures

Who writes?

Sound, hands on experience and knowledge of the tasks

Take input from a no. of number greatly enhance usefulness

of the procedures Writing SOPs doesn't require a

degree in ‘alchemy’ Most important things author of

a SOP can bring to word processor common sense logic

Who writes?

Must convey a clear instruction Not only must the user understand the instruction

must also be prepared to carry it out The logical step is to let the user, as far as possible,

write the SOP, in collaboration with the Trial Manager / Investigator or CRA

Brings in familiarity, ownership and prevent awakwardness

An improved sense of responsibility for obligation to use and comply with the SOP

What format should be used?

"Just spill your guts to your computer and don't worry about the format"

Format can always be added later If there is a fool proof template that can be

given - might help ease some of anxiety of novice author

Format…example

Table of contents

1 Purpose.................................................................................................22 Scope ................................................................................................. 23 Abbreviations .......................................................................................24 Definitions.............................................................................................35 Responsibilities.................................................................................... 56 Procedure............................................................................................ 66.1 Clinical Trials, phase I-III ................................................................. 66.2 Adverse Events Reported Spontaneously on Marketed Products76.3 Post-Marketing Studies ................................................................... 96.4 Named Patient Supplies.................................................................. 97 References..........................................................................................

Annexures/ Appendices/ Attachments: Forms / checklists Change log

What format should be used?

Easier to edit SOPs with default formatting rather than a doc that has many extra tabs and returns added in an attempt to emulate accepted format

Many new authors - involved in correct formatting - content suffers

Don't rely on spell check to find all misspelled words If you use "fur" instead of "for," spell check will blithely

accept it Use grammar check with care- not find all goofy little

grammar faux pas that can occur when normal people put word to page

If a word is changed using the Replace command, be sure to individually approve each replace. Universal replacement is quick and easy - sometimes too easy - and produces fodder for News

Before & After Writing…….

Identify need for new SOP Gather Input for SOP Create SOP Review and Approve SOP Provide training on SOP and distribute

SOP to relevant audience Revision and Deviations of SOPs Quality Assurance Glossary

What should SOP cover?

The no. of SOPs The arrangement of material in SOPs The level of detail in the SOPs Depend upon entirely on the organization and its related role in CT e.g., the SOPs at the

sponsor’s site will be different than those at the Trial Site requirement and role of the staff members executing their work Brief outline which in general all the SOPs must cover-

· A descriptive title and indication of the SOP’s position in the total collection.· Date when the SOP became operative· The edition number and a statement that this edition replaces an earlier edition from an earlier date· The exact distribution of SOPs· The signature of the person responsible for writing the SOP· The signature of the person responsible for authorising the SOP· In some contexts the purpose of the SOP


Title sufficient information about the contents placed prominently on page

to allow the user to identify find it easily

Distribution list directs - to place where it will be used distributed at all related places of its function strict check should be kept on nos. of SOPs

issued and distributed at each working area


Singatures Signature of the person

responsible for writing - shows that - SOP is complete & correct

Should an auditor or for that matter any one else have a query about the content of SOP, this would be the person in contact

Signature of the person responsible for authorizing - shows that SOP is operative

Step-by-Step Approach

8 steps1. Mapping the SOP 2. Use of language and Scripting the SOP3. Editorial responsibilities of SOPs4. Authorizing the SOPs5. Distributing and Archiving the SOPs6. Training of the SOPs7. Alteration in SOPs8. Review of the SOPs

Step-by-step approach Step 1 - Mapping SOPs

Process mapping – laying out all the steps in a currently used process analyzing -with goal of making it more efficient and easier to follow

Involves taking each step in process & “mapping” it into a process chart All people - involved in doing task should be involved in mapping it into a process

chart - free and open discussion. Often discovered during this process - involved people do not do things same

way & have very different ideas about how current process works and how it should be done in the future

SOPs cover all aspects of a CTprotocol preparationethical approvalassessing and monitoring trial sitessafety data reportingchecking data integrityclinical report writingdatabase preparationvalidating computer systems

all the records are generally created electronically FDA’s Draft Guideline - ‘Computerized System used in Clinical Trials’

Step-by-step approach

SOPs do not have to “fit into a box”. Formats can vary. Presentation techniques such as flow charts, diagrams, narratives, tables and bulleted lists should be considered in addition to the traditional text and paragraph formats. Presentation might vary, and should address conditions pertinent to the individual environment. Procedures should be presented in a format that will work for the institution and address specific needs in various ways. The goal is to have an easily understood procedure that the Clinical Research Staff will clearly understand and utilize.

Step-by-step approach Step 2 - Use of Language & Scripting the SOP

written in the language which is understandable by the staff or people dealing with it

If for regulatory purposes or for foreign auditors language has to be in a foreign language, an authorized translation of the SOP in the local language which is understandable by its users must be readily available at the working area

Authorities, clients & colleagues must be prepared to accept translations- after all- not primary target

must communicate their message effectively -must be crystal clear on who is to do what.

almost seems too obvious to write, but many SOPs are difficult to read.


The rule of thumb for writing instructions in SOPs is these- Use short active sentences Use simple words & terms where possible Write sentences as instructions:’ do this, do that’ Write instructions in right order-so operator knows

when to do appropriate task Separate instructions from gen info ,either

typographically or by putting gen info in a foot note Limit amount of info per page-max 10 different

actions Use diagrams wherever appropriate Give sources and references at the end


Step 3 - Editorial Responsibilities of SOPs It is possible for each dept or section to write, authorize

&produce SOP’s in isolation. For company or sponsor----advantageous to give someone editorial responsibilities

Management decides whether or not to edit SOP’s. Suitable editors might be an interdepartmental GCP committee or some of the QAU (Quality Assurance Unit) personnel

Their duties would include checking a new SOP for- Style and format The edition number Consistency of content in context with relevant SOPs from

other departments Compliance with policy, ICH GCP and other regulatory

requirements

Step-by-step approach Step 4 - Authorizing the SOPs

No SOP is a SOP without proper authorization Purpose is to decide on an appropriate method for a given

procedure, standardize the performance of the procedure & communicate these decisions to everyone involved

Most effective authorization is done by someone with organizational influence, specialist insight and knowledge of ICH GCP

Rational approach - let management, in its policy, mandate use & production of SOPs

Same policy -can delegate responsibility for authorization to person in charge of each specialist area defined as ‘management ’in this special context

Departmental SOPs then specify which named individuals are empowered to authorize SOP’s in their area

Step-by-step approach Step 5 - Distributing & Archiving the SOPs

Each dept or for that matter section (e .g sponsor ’site or Trial site) administers its own collection of SOPs & must identify (by the management) who is responsible for their distribution and withdrawal

Responsibility for typing and copying of SOPs will depend on capacity in different depts When requisite no. of SOPs have been produced, before distribution, they should be

stamped ‘DO NOT COPY’ and ‘CONTROLLED COPY’ with coloured stamp, or some other technique to distinguish between the original from photocopied versions.

original SOP should be kept by QA or a responsible management representative in a secure place

Historical or expired SOPs whose new versions have been issued - properly archived with ‘ARCHIVED’ stamp on original SOP

Should be kept in a designated place with controlled entry called ‘Archives’ can be retrieved from the ‘Archives’ for the purpose of reference or audit

whenever reqd with a proper documentation and the SOPs should be re-archived after the job is finished.

A management designated person called ‘Archivist’ should be responsible for managing archives

All photocopies of expired SOP - destroyed immediately after its new version comes in effect

to reduce confusion for staff in working by existence of 2 different methods floating simultaneously

Step-by-step approach Step 6 - Training of the SOPs

Training on SOPs is often last thing that people think about once SOP is written When SOP goes into effect there is often a great sense of relief

frequently case that staff does not receive adequate training on the SOPs-purpose of SOPs - remains unfulfilled

QA/ Monitors / CR Managers & management should see to it that there is continuous training of SOPs among staff

trainings should be documented properly and all records - training log must be maintained in the staff training record

effective date - must be 2-3 days after it is authorized Give sufficient time for staff to read & understand the SOP before it is

actually implemented in system. effective date should be clearly specified - so that staff is aware of it

Also staff training on FDA’s 21 CFR Part 11 and related guidelines on electronic records should be undertaken

Formal and continuous training sessions should be taken by the QAU, CRA and CR Managers

increase SOP awareness among staff and also continuous review will help in amending SOP, if reqd

Step-by-step approach Step 7 - Alterations in SOPs

When a mistake in an SOP is found, it is tempting to alter the text by hand

especially tempting when the SOP is newly issued or if the change is only in the distribution list

Such alterations are dangerous as no one knows whether comments appear in all SOPs of that edition how long they have existed there whether anyone has modified their working routine as a result, or

whether data has been compromised Detection of such actions must prompt inquiry- if alteration is

necessary- will need to update electronic SOPs- must be a secured system of change control and

rights to modify SOPs should be properly reflected in audit trail procedure of updating a SOP must reflect in the appropriate SOP both

electronically and manually (if practiced)

Step-by-step approach Step 8 - Reviews of SOPs

should be regularly reviewed and updated to ensure that they encourage efficient working practices that comply with the ever increasing requirements, improvements and government regulatory framework that have to operate within

Prudent for management to introduce a scheme for automatic review - date of next review should be reflected so that everybody is aware of next review date and are

ready with their suggestions and improvements If no changes are necessary this decision should be

recorded but still version no. should be changed to reflect that review did happen

Parties in a Clinical Trial

Sponsor

Investigator Patient

Regulatory Authorities

Ethics Committee

ClinicalTrial

The End………

Thanks for the Attention…….

Pl feel free to discuss or ask questions

Extra Slides

Documents

Writing SOPs