Standard operating procedures (SOP) - Back Bone of Pharmaceutical Industries

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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.

2.  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.

3. 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.

5.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.

Table 1: SOP and decision for format type

Sr. No.

Does SOP involve many decisions?

Does SOP consist of more than 10 steps?

Best format for writing SOP

Examples

1

No

No

Simple sequential steps

SOP for balance calibration

2

No

Yes

Sequential steps along with Pictorial diagrams

Entry / Exit procedure

3

Yes

No /Yes

Sequential Steps with Flow chart

SOP for deviation management

Requirement for document identification and control, accountability and traceability responsibility must be included with every SOP; this can be achieved by providing consistent format.

Since there is no FDA approved format for a SOP, however there are common expectation within industry and from the FDA that assure accountability and traceability and consistency of the documents, when choosing format for a procedure consider the following:

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.

6. 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.

Flow Diagram for SOP preparation and implementation

  Figure 1 : Flow Diagram for SOP preparation and implementation

Following are 10 ideas to keep in mind while writing Standard Operating Procedures (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

 

References:

1.PDA Letter, May 1999.

2.D. Gingell, Pharm. Technol. Europe (4), 2001.

3.J. Nally, R.G. Kieffer, and J. Stoker,“From Audit to Process Assessment—The More Effective Approach,” Pharm. Technol. 19 (9), 128–140 (1995)

4.C. De Sain and C.V. Sutton,” Standard Operating Procedures: Content, Format, and Management,” Pharm. Techno. 20 (10), 110–116, 1996.

5. T. Dunford,“Taking the Myth Out of Documenting Work Instructions,” Quality Progress (12), 1998. 7. CGMP Preamble, Federal Register 43 (190), p. 45033 (29 September, 1978). PT.

6.G.Kieffer Robert “Procedures Improving Their Quality”, Pharmaceutical Technology January 2003, p. 64-72.

7.Guidance for Preparing Standard Operating Procedures (SOPs) EPA QA/G-6.

8.Standard Operating Procedures: A writing Guide For Dairy farm business by Richard Stup.

9. Escoe,”The Practical Guide To People friendly Documentation”(ASQ Qualtiy Press ,Milwaukee, WI,2001)PP99-114

Authors:

Sanjay k Jain

 

 

 

 

 

Sanjay k Jain

Corresponding Author

Nikhil Bhatwadekar

Nikhil Bhatwadekar

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Comments

Eswar GsnkRao's picture

U did the presentation in most meaningful and understandable manner. Its simply GooD.
Vast collection is being observed through your blog. Actually we are planning to prepare SOPs for laboratory instruments in our college. Will U plz help me in that sense.
I mean to ask you any model SOP for instruments like Hot air oven or autoclave.
Go on keeping such informative and useful reviews.
eswar :-)

Regards

ESWAR :-) 

Nikhil Bhatwadekar's picture

Dear Eswar,

Thanks for your feed back,its our plesure to help u, kindly let us know list of instruments along with the model.

Eswar GsnkRao's picture

Shortly I will respond to you.
B'coz right now I am not sure about models of all the instruments, I will look after and intimate to you.
Thanks for your consideration of my request....
Glad to have such a helping hand..
eswar :-)

Regards

ESWAR :-) 

JuliaKnight's picture

Dear Nikhil, My colleagues and I are very impressed by your ability to delineate the basic Standard Operating Procedures of the Pharmaceutical Industry. It appears as though you have much expertise in this field. Do you have any experience with Cold-Chain SOP Remediation/ Revision? If so, we would be very interested in speaking with you about doing some freelance SOP consulting for our company. Please call me at 1-508-588-2008 if this is something you may be interested in. Best regards, Julia C. Knight Asaman, Inc.
Julia C. Knight
Lakshya's picture

Dear Sanjay and Nikhil, This is a good effort to educate all about the concepts of SOP. This review can help all students, teachers and industry people. I will rather say you have provided good back bone for studying SOP's.
I especially liked the part "Following are 10 ideas to keep in mind while writing Standard Operating Procedures"
Can you please specify that is there any difference for preparing SOP's as per the different regulatory agencies or while getting certified the lab/ industry from specific organizations like FDA, WHO etc?

Eswar GsnkRao's picture

I got the details of some of the instruments in our lab and hereby mentioneing the same as per your suggestion and awaits for your kind reply.

Dear Nikhil, U can mail me the available inputs to eswarmpharm@yahoo.com

1.HOT AIR OVEN: DIGITAL TEMPCON
Model No. DTC 201
Make: Temp Star

2.HOT PLATES
Make: Temp Star

3.WATER BATH
Make: Temp Star
Model No. Digital KW203C

4.DIGITAL BALANCE
500 mg – 300 g capacity
ed: 10 mg
Make: Excon

5.DIGITAL pH meter
Make: Environmental and Scientific Instruments
Model: 011G

6.Melting Point Apparatus
Make: Temp Star

7.CENTRIFUGE Apparatus
Make: Temp Star

8.Anamuel Electronic Balance
Capacity: 0.02g – 300 g
Sensitivity: 10 mg

9.Laboratory Centrifuge Apparatus
Make: REMI Company
Mdel: R4C

eswar :-)

Regards

ESWAR :-) 

Pushpendra Jain's picture

Hi Eswar Did you get details regarding your instruments SOP coz i have same instruments here and need their SOP

Mind Hunter; Jiyo aur Jine do

Eswar GsnkRao's picture

Dear Jain, Your caption is thrilling! Ofcourse i did some transactions with Mr. Nikhil and finally prepared by my own the SOPs for the equipment available in our institute. The basics presented by Mr. Nikhil team were also helpful to my requirement. If you are interested we will co-ordinate to serve your purpose. Mutual helping is no way a problem. Feel free to get in touch.

Regards

ESWAR :-)