Standard operating procedures (SOP) - Back

Bone of Pharmaceutical Industries

1. What is Sop
In the face of a challenging regulatory environment, some leading Pharmaceutical
companies have found ways to improve quality and costs significantly. To drive this kind
of beneficial change, companies must first create a culture where quality objectives are
transparent, well understood, and undoubtedly these goals can be achieved by following
certain sets of procedures called as “Standard Operating Procedures” (SOP). Procedures
are essential for any plant’s effectiveness and efficiency, and they are regulatory
requirement in the Pharmaceutical Industry. A typical Pharmaceutical Industry has an
average of 1200- 1300 SOPs. A Parenteral Drug Association (PDA) survey found that a
typical pharmaceutical company must manage an average of 1250 CGMP-required SOPs
and that the average maintenance burden is 15,000 h per firm.
A Standard Operating Procedure (SOP) is a set of written instructions that document a
routine or repetitive activity which is followed by employees in an organization. The
development and use of SOPs are an integral part of a successful quality system. It
provides information to perform a job properly, and consistently in order to achieve pre-
determined specification and quality end-result.
Need Of Sop
SOPs detail the regularly recurring work processes that are to be conducted or followed
within an organization.  They document the way activities are to be performed to facilitate
consistent conformance to technical and quality system requirements and to support data
quality.  They may describe, for example, fundamental programmatic actions and technical
actions such as analytical processes, and processes for maintaining, calibrating, and using
equipment. Sops are intended to be specific to the organization or facility whose activities
are described and assist that organization to maintain their quality control and quality
assurance processes and ensure compliance with governmental regulations.
SOP must contain step by step instructions that employ must refer in daily work to
complete various tasks more reliably and consistently. SOP makes clear about followings -
·What is the objective of SOP (Purpose)
·What are applicability and use of SOP (Scope)?
·Who will perform tasks (Responsibility)
·Who will ensure implementation of procedure (Accountability)
·How tasks will be performed (Procedure)
Procedures are not an end in themselves—they do not guarantee good performance or
results. More important are well-designed systems and processes, qualified employees,
and a motivating company culture. Procedures support process people–environment but
do not create processes, qualified people, or a good working environment.
Benefits Of Sop
1.To provide people with all the safety, health, environmental and operational
information necessary to perform a job properly. Placing value only on production while
ignoring safety, health and environment is costly in the long run. It is better to train
employees in all aspects of doing a job than to face accidents, fines and litigation later.
2.To ensure that production operations are performed consistently to maintain quality
control of processes and products. Consumers, from individuals to companies, want
products of consistent quality and specifications. SOPs specify job steps that help
standardize products and therefore quality.
3.To ensure that processes continue uninterrupted and are completed on a prescribed
schedule. By following SOPs, you help ensure against process shut-downs caused by
equipment failure or other facility damage.
4.To ensure that no failures occur in manufacturing and other processes that would
harm anyone in the surrounding community. Following health and environmental steps
in SOPs ensures against spills and emissions that threaten plant neighbors and create
community outrage.
To ensure that approved procedures are followed in compliance with company and
government regulations. Well-written SOPs help ensure that government regulations are
satisfied. They also demonstrate a company's good-faith intention to operate properly.
Failure to write and use good SOPs only signals government regulators that your company is
not serious about compliance.
6.To serve as a training document for teaching users about the process for which the SOP
was written. Thorough SOPs can be used as the basis for providing standardized training for
employees who are new to a particular job and for those who need re-training.
7.To serve as a checklist for co-workers who observe job performance to reinforce proper
performance. The process of actively caring about fellow workers involves one worker
coaching another in all aspects of proper job performance. When the proper procedures are
outlined in a good SOP, any co-worker can coach another to help improve work skills.
8.To serve as a checklist for auditors. Auditing job performance is a process similar to
observation mentioned in the previous item only it usually involves record keeping. SOPs
should serve as a strong basis when detailed audit checklists are developed.
9.To serve as an historical record of the how, why and when of steps in an existing process
so there is a factual basis for revising those steps when a process or equipment are
changed. As people move from job to job within and between companies, unwritten
knowledge and skills disappear from the workplace. Properly maintained written SOPs can
chronicle the best knowledge that can serve new workers when older ones move on.
10.To serve as an explanation of steps in a process so they can be reviewed in accident
investigations. Although accidents are unfortunate, view them as opportunities to learn how
to improve conditions. A good SOP gives you a basis from which to being investigating
accidents.
4.  Sop – Writing Styles
SOPs shall be written in a concise, step by step,
easy to read and follow format. The
information presented should be unambiguous
and not complicated. The active voice and
present verb tense should be used. SOP shall
be simple and short. Information should be
conveyed clearly and explicitly to remove any
doubt as to what is required. Flow chart shall
be used to illustrate the process being
described.
5.  Format And Content Of Sop
When generating a SOP one can choose
number of different ways to organize and
format them. There are some factors which
determine what type of SOP to use or create.
(Refer Table 1)
How many decisions will user need to make
during process?
How many steps and sub steps are there in
procedure?
Routine procedures that are short and require
few decisions can be written using simple steps
format. Long procedures consisting of more
than 10 steps, with few decisions should be
written along with graphical format or
hierarchical steps. Procedures that require
many decisions should be written along with
flow chart.
 ponsibility must be included with every SOP; this can be achieved by providing consistent fo
ation within industry and from the FDA that assure accountability and traceability and consis

Sr. Does Does SOP Best format for Examples

No. SOP consist of writing SOP
involve more
many than 10
decisio steps?
ns?

1 No No Simple SOP for balance

sequential calibration
steps
2 No Yes Sequential Entry / Exit
steps along procedure
with Pictorial
diagrams
3 Yes No /Yes Sequential SOP for deviation
Steps with management
Flow chart
A)Company Name and Pagination
The company name and pagination (e.g. page 4 of 7) must appear on every page.
B)Title
The title should be descriptive. The title should use directive language to declare what is
being done to what. A SOP titled “Compression Machine” is not descriptive of the
procedure’s content. A more appropriate title would be “OPERATION OF COMPRESSION
MACHINE”.
C)Identification and control
Procedures must be easily identified by giving unique number and version number.  This
identification number of the SOP supports accountability of the document throughout
the facility and over time as it changes.
D)Review and Approval
All Sops shall have space for signature of initiator (the person who has written the SOP)
Reviewer (The persons who has reviewed the SOP) and approver (Quality Assurance Head
of the organization).
E)Purpose
The purpose or objective of the procedure should restate and expand well written title.
Expand or qualify the directive language used in the title (e.g. to describe the operation
procedure of compression machine)
F)Scope
The scope should provide limits to the use of procedure. The scope shall be written in
such a way that it answers following questions.  Are there certain samples that are
appropriate to test by this method? Do these operations apply only to certain equipment
or certain departments? Is there a limit to the capacity, volume, or throughput of the
procedure? State to what areas this procedure does apply and does not apply?
G)Responsibility
Who is responsible for performing the work described? Who is responsible for
implementing the procedure?
H)Procedure
Describe the procedure in a step by step, chronological manner.  Use active verbs and
direct statements (e.g. check the cleanliness of machine and tools)
I)Checklists  
Many activities use checklists to ensure that steps are followed in order.  Checklists are
also used to document completed actions. Any checklists or forms included as part of an
activity should be referenced at the points in the procedure where they are to be used
and then attached to the SOP. In some cases, detailed checklists are prepared specifically
for a given activity.  In those cases, the SOP should describe, at least generally, how the
checklist is to be prepared, or on what it is to be based.  Copies of specific checklists
should be then maintained in the file with the activity results and/or with the SOP. 
Remember that the checklist is not the SOP, but a part of the SOP.
. Sop Process
A) Sop Preparation
The organization should have a procedure in place for determining what procedures or
processes need to be documented.  Those SOPs should then be written by individuals
knowledgeable with the activity and the organization's internal structure.  These
individuals are essentially subject-matter experts who actually perform the work or use
the process.  A team approach can be followed for better results.
SOPs should be written by an individual who performs the tasks routinely or someone
who is directly responsible for the performance of the task.
Ideally, SOP’s should be written by teams that include some or all of the following
people:-
·Those who will perform the job
·Those who will perform maintenance on equipment involved in an SOP
·Engineers or others who design equipment and processes
·Technical initiator
·Safety personnel
Environmental personnel
·Equipment manufacturers
Team writing accomplishes several goals
besides just producing an SOP:
1. It ensures that comprehensive knowledge
acquired from different perspectives is applied
to the SOP.
2. It creates "buy-in," which increases the
likelihood that the SOPs will be implemented
under the guidance of the initiator.
3. It trains trainers the people who write the
SOP. Having participated in in-depth decision
making about the SOP, initiator know it
intimately and are more likely to be effective
trainers (coaches).
4. It involves people from diverse parts of the
operations as a whole, which helps ensure that
when new and modified processes are
implemented, someone goes back and updates
the SOP.
5. It encourages employees to follow the SOP
and listen to the coaches because the
employees know that the initiator invested
time and effort on behalf of the employees.
Writing in teams do not have to sit together to
write. They can write or edit parts of an SOP
independently and then one person can
combine the individual contributions. Once
combined, circulate the draft SOP for review
among the initiator before editing a final draft
for review by supervisors and subsequent
supervised testing by employees. Ideally a
writing team should meet at least once in the
beginning of a project to establish writing
objectives, targets and responsibilities, but
then can work semi-independently with one
person serving as coordinator. Most
importantly, SOPs should be reviewed by
several people qualified to evaluate the SOP in
terms of its completeness and clarity of subject
matter. Refer Below mentioned flow diagram
for the preparation and implementation
process of SOP.
1. How much someone knows about an entire process or job affects the way he or she does that
job. Incorporate safety, health and environment into the traditional how-to-operate or how-to-
do steps. This teaches the person comprehensively so that he or she has a complete picture of
the responsibilities for doing a job properly. This knowledge base simplifies follow-up training.
2. Write an SOP to be as long as necessary for a specific job. All jobs differ in the number of steps
required to complete them properly. Short changing someone by providing short and
incomplete SOP sets up failure. Write an SOP to satisfy the definition of SOP, not a standard
company format that no one has thought about in years.
3. People tend to ignore long SOPs because they cannot remember more than 6 to 12 steps. If
your SOP goes beyond 10 steps, consider these solutions:
o Break the long SOP into several logical sub-job SOPs,
o Writean accompanying shortened SOP that lists only the steps but not detailed explanations of
those steps, and
o Make the long-form SOP a training document or manual to supplement the shorter sub-job
SOPs mentioned earlier.
4.Prepare the longer comprehensive training SOP first to get a picture of what training is
needed. Then decide how to break it into shorter sub-job SOPs. Writing sub-job SOPs first, and
then trying to put them together, may leave out linkage steps that make sub-jobs
interdependent.
5. Write SOPs for people who perform under different interpersonal circumstances.
o Write some SOPs for people who work alone.
o Write some SOPs for two or more people who work together as a team.
o Write some SOPs for people who will supervise other people doing a job.
o Write some SOPs for people who not familiar with rules generally understood by your
employees. For example, you may write for contractors, vendors or suppliers.
6.Considern the work culture within which people work. If you write for people in a culture in
which shortcuts are accepted practice, explain the reasons behind certain steps so that SOP
users will understand the importance of following all the steps in the proper order.
7. Consider the age, education, knowledge, skill, experience and training, and work culture of
the individuals who will be performing the SOP steps.
8. Keep in mind that many people do not read all the steps before starting on step one. Many
people read one step, perform it, read the next step, perform it, and so on. To try to get around
this habit, forecast future effects and steps at certain points in the SOP to tell reader things they
should know in advance, such as upcoming steps that require caution, precision, timing,
assistance, and personal protective equipment.
9. Once you have completed writing an SOP, have several workers test it and give you feedback.
If you did not consult safety, health and environmental experts prior to writing the SOP, have
them observe the SOP being tested so they can add comments.
10.  Review the effectiveness of SOPs after a few weeks and make necessary changes if in-the-
field practice suggests that descriptions should be improved. 
11. Review SOPs when processes and equipment are changed.
When new equipment is installed, take the opportunity to write a new SOP, incorporating the
good from the old, and adding what is necessary to satisfy the new equipment.
B) SOP Review and Approval
SOPs should be reviewed by one or more individuals with appropriate training and experience
with the process especially helpful if draft SOPs are actually tested by individuals other than the
original writer before the SOPs are finalized.
C) Frequency of Revisions and Reviews
SOPs need to remain current to be useful.  Therefore, whenever procedures are changed, SOPs
should be updated and re-approved.  If desired, modify only the pertinent section of an SOP and
indicate the change date/revision number for that section in the Table of Contents and the
document control notation.   
SOPs should be also systematically reviewed on a periodic basis, e.g. every 1-2 years, to ensure
that the policies and procedures remain current and appropriate, or to determine whether the
SOPs are even needed.  The review date should be added to each SOP that has been reviewed. 
If an SOP describes a process that is no longer followed, it should be withdrawn from the current
file and archived
D) Implementing SOP
The most important step for implementing the SOP in working area, train or retrain the user.
Every one should follow the procedure exactly with each and every step in detail, it is very
important to train the user otherwise individual may interpret meaning indifferent ways.
While training the user trainer should share the reason WHY, SOP must performed correctly.
People are much more to follow when they understand importance of procedure .Trainer should
explain and demonstrate how each step in the SOP will be performed and should assure them
this will increase Quality of product by providing safety and accuracy which will ultimately
increase the confidence of the user.
E) Management of SOP
Organization shall have SOP on Preparation, approval, revision and control of standard Operating
Procedure for better control and management of SOPs. Generally, administrative aspects of the
SOP system such as distribution and filing are well managed. On the other hand, overall system
management, frequently characterized by the lack of a system owner, is generally poor. If a
system owner exists at all, his or her responsibilities are limited. Ideally a system owner
·Eliminates obsolete SOPs.
·Ensures that SOPs meet their quality requirements and are user friendly.
·Manages SOP change controls.
·Distributes SOPs.
·Ensures that SOPs are current.
·Ensures that new or changed SOPs are valid only after training has occurred and provides
training about the SOP system.
·Measures system performance and periodically reports results to management
·Continuously improves the system.
7.  FDA Audit Findings
Code Of Federal Regulations for drug product manufacture’s states (Subpart F, CFR Part 211.100)
“There shall be written procedure for production and process control designed to assure that
drug product have the identity, strength, quality and purity, they purport or are represented to
possess.”
The Code of Federal Regulations for medical device manufacturers and other related regulated
entities (Title 21, CFR Part 820) states repeatedly that firms must “establish and maintain”
procedures. To do so, companies should define, document (either on paper or electronically),
and implement standard operating procedures (SOPs). Additionally, companies must then follow
up, review, and revise these documents as needed.
The intent here is simple: Companies must ensure that their organization develops and manages
operationally sound procedures that are compliant with the law. FDA audit findings in 2006
clearly indicate that ensuring establishment and maintenance of procedures is fundamental in
FDA’s inspection strategy. During inspections in 2006, the agency commonly observed that
companies failed to keep accurate records and that they neglected to establish and maintain
procedures.
8. Conclusion:
SOPs serve as a fundamental means of
communication for all levels of the
organization. Not only do they involve
employees departmentally, but they also allow
management and employees to gain a cross-
functional view of the organization. This
approach encourages employees to think
about how process change may affect other
functional areas. A good system forces
Employee to think through processes and
examine how Procedure might affect product,
personnel, production, and equipment. It shall
be noted that the Best written SOPs will fail if
they are not followed.
 Annexure of Sample SOP:

Standard Operating Procedure

Company Name and Address:     Page No: X of Y

 
 
 

Title : SOP No:

 
  Revision No:
  Review Period:

Prepared By Reviewed By Approved By

     
 
 
 

Objective
 
 
 

Scope
 

Responsibility
 
 

Procedure