Deviation/Nonconformity Report SOP

Standard Operating Procedure

Deviation / Nonconformity Report SOP

Document No.: QA-034-03

Preparation Samere Naimi (QA expert) (Date) 2021/11/23

Approval Ahmad Asemi nia (CEO) (Date) 2021/11/23

Mohadese Hosseini Zabet (Authorized

Authorization person/QA manager) (Date) 2021/11/23

Effective From:

Revision date:

Purpose

The purpose of preparation of this SOP is to provide a codified method for reporting, documenting, evaluating,
managing, and resolving deviations / non-compliance with approved GMP guidelines or requirements.
Deviation/Nonconformity Report SOP

Function

The use of this SOP in all sections is to report deviations from approved guidelines or GMP requirements,
which can include the following:
Manufacturing processes, equipment and devices, support services(Utility), raw materials, intermediates,
pharmaceuticals and pharmaceutical products, quality control, packaging, warehousing, distribution and other
deviations from the approved guidelines or GMP requirements.
Results beyond the acceptance limit of QC tests, such as stability results and other tests, do not include
deviation report.

Responsibility

It is the responsibility of all staff to implement this SOP so that they report it to the division manager as soon
as they notice a deviation / nonconformity.
The department manager is responsible for immediate action (correction), confirmation of deviation and
reporting it to the quality assurance department.
The quality assurance expert is responsible for evaluating the deviation / non-compliance report and
conducting subsequent reviews.
The final review and approval of the report is the responsibility of the authorized person / quality assurance
manager.

Safety considerations

Not applicable

Devices and equipment

Not applicable

Materials and solutions

Not applicable

Primary actions

Not applicable

Abbreviations / Definitions

SOP: Standard operating procedure

Deviation: Any error, unforeseen change, carelessness in the execution of processes or violation of approved
GMP guidelines or requirements that has a potential impact on the process or product quality is called
deviation.
Non-conformity: Any non-compliance or non-compliance of a material with the defined properties /
specifications is called non-compliance.

CPP: Critical Process Parameter

Immediate action or correction: Any action taken to correct the observed deviation or non-compliance

CAPA: Corrective action/Preventive action

Corrective action: Any action taken to eliminate the causes of the deviation / non-compliance
has occurred
Preventive action: Any action to identify and eliminate potential causes of deviations / non-
.conformances that may occur
Deviation/Nonconformity Report SOP

Research and Investigation: A logical or scientific documentary review of data related to all
qualitative events that lead to the identification of the root cause and corrective and preventive
.measures
Procedure
Deviation / non-conformity is in fact distancing from an approved instruction that can be occurred for -1
production processes, batch record, quality control, in-production tests, environmental monitoring, equipment
and devices, support services, primary material specifications, intermediate, drug substance and
.pharmaceutical products, packaging, warehousing, distribution, etc
:Deviations are handled according to the following steps -2

I. Event Detection
II. Decision Making Process/Deviation Categorization
III. Deviation Treatment
IV. Root cause investigation
V. Corrective action/Preventive action
Event detection

As a basic requirement, staff should be aware of potential adverse events and know exactly what to do in
terms of documentation and information.

How personnel react and make decisions can be categorized, recorded, and systematically devised based on
their risk and impact on the product.

Decision making / deviation classification process

The classification of the type of deviation / non-compliance can be determined according to the diagram in
appendix 1 and based on the risk assessment and the answer to the following question.

Does the reported event affect the characteristics of the product or the main parameters of the production
process or the quality of the product?

Is the reported event contrary to the procedure of an approved instruction or an approved quality certificate?

Have similar items from this report been repeated before?

If the answer to all the above questions is no, the reported event is not considered a deviation / non-
compliance and is considered as an event / incident and does not need to be documented in the production
record sheets, the logbook etc. like a power outage in the warehouse and remaining within the temperature
range of the warehouse

If the answer to the first or second question is yes (even if it is doubtful), the received report is considered a
deviation and should be classified into one of the critical, main or minor types based on its impact on the
patient's health.

The classification of deviation is based on the effect of deviation on the safety, integrity, strength and quality
of the product. Classify according to the following definitions:

Minor deviation: Any deviation that does not affect the characteristics / specifications of the pharmaceutical
product or critical process parameters (CPP) or devices and equipment that are important in the process or
control. Such as non-compliance with the FIFO / FEFOT principle, use of limited capacity scales for weighing
inlet raw materials, out-of-range pressure differences in Class D washing room, use of staff with insufficient
training to clean the warehouse.

If a minor deviation is repeated in a significant number, it should be classified as a major deviation and
managed according to the steps related to the main deviations.
 Deviation/Nonconformity Report SOP


Main deviation: Any deviation that affects the characteristics / specifications of the pharmaceutical
product, or critical process parameters (CPP) or devices and equipment that are important in the
process or control, but leads to a risk or serious damage to the patient is not classified as a major
deviation and needs immediate action, investigation, documentation and corrective / preventive
action.
Such as using an unapproved standard to test an effective ingredient or medicinal product,
performing sterility testing by staff with insufficient training, conducting production without line
inspection, performing filter integrity testing using equipment whose installation qualifications are not
documented, staff misconduct In the critical aseptic process, the out-of-range pressure difference
defined in the aseptic filling environment, the out-of-range operational parameter for a non-critical
parameter, the use of untrained personnel to separate approved and rejected raw materials in the
warehouse.
 Critical Deviation: Any deviation that affects the characteristics / specifications of a pharmaceutical
product, or critical process parameters (CPP), or devices and equipment that are important in the
process or control, leading to a risk or serious injury to the patient is classified as a critical deviation
and requires immediate action, investigation, documentation, and corrective / preventive action.such
as the use of a drug that has expired or been rejected, unavailability or impossibility of the result and
the history of sterilization of materials that are in contact with the product during the aseptic filling
process, incomplete inactivation process in fermentation, out-of-control temperature in the
detoxification stage.

Deviation management

 Minor deviations
 Description of Deviation: Adequate approval of deviation requires well-documented objective
evidence that is written in a concise and clear manner and involves time, place, and person involved.
 Immediate action: Corrections are immediate action based on a simplified deviation analysis.
Immediate action, if possible, should be approved by the quality assurance department before
implementation, and if not possible, should be approved by the department manager before
implementation. And be approved by the Quality Assurance department as soon as possible. Minor
deviations, such as major and critical deviations, do not necessarily require investigation to identify
the root causes of the problem.
 Some modifications may require change control, in which case I, the request must be submitted to
the quality assurance department.
 Evaluation of effectiveness: The effectiveness of the immediate action (correction) performed, Is
expressed based on the immediate result of the action taken, which must be recorded in the
deviation / non-compliance reporting record sheet and the final result must be approved by the
quality assurance expert and authorized person / quality assurance manager.

Description of deviation Immediate action (Correction) review of immediate effectiveness and closing the report

 Critical / major deviations

 Definition of Deviation: The description of the main and critical deviations should be carefully
described in the deviation / non-conformity report record sheet so that efficient investigation can be
carried out.
 Immediate action: Corrective action must be confirmed by quality assurance before performing.
Deviation/Nonconformity Report SOP

 Evaluation of the effectiveness of immediate action: The effectiveness of the immediate action
taken must be approved by the quality assurance department.
 In case of application of production stop: if necessary, the production batch number affected by the
reported deviation should be specified and kept separate from other batch numbers.
 Determining the root causes using systematic tools (maximum 30 days): Investigating the root
causes is a powerful tool used to improve the quality. Among the various tools available to
investigate the root cause, "5 why" and "Ishikawa fish bone diagram" are the simplest and most
widely used.
 "5 why" refers to a series of frequently asked questions (ie, each answer is asked again with a "why",
usually 3 to 5 times). This tool allows a full understanding of the underlying causes of the deviation,
which may be related to a systemic problem.
 Fishbone diagram (Figure 1) is a type of cause-and-effect analysis in which the main product /
process of the backbone, the effect of deviation / nonconformity occurred, and the secondary spines
are various factors or causes that can cause deviation (such as material, controls, personnel,
equipment, procedures, etc.)
 Impact on process, equipment, system, or product should be evaluated in relation to other similar
situations that may occur. Vertical analysis to identify the root cause should always be accompanied
by horizontal analysis of potential events.
 Investigations into the root causes of deviations should be conducted in a systematic and
professional manner, in a manner approved and adequately trained by personnel. Research should
be based on past data and knowledge.

Figure 1

Determining corrective and preventive measures and reviewing their effectiveness

The root cause investigation process is a key step in addressing major and critical deviations because it
provides objective evidence for the implementation of corrective and possibly preventive measures as
part of the CAPA system.
Corrective actions are taken to eliminate the root causes of deviations and should be based on thorough
research. Pre-implementation corrective actions should be approved by the quality assurance department
and their effectiveness should be documented.
Corrective actions can be transferred to a standalone CAPA system (according to QA-035 guidelines) to
avoid unnecessary delays in closing the diversion. This standalone CAPA system should include tracking
all required actions by a pre-approved CAPA designer and evaluating effectiveness.
The following chart (Chart 2) can be considered as part of the overall CAPA strategy:
Deviation/Nonconformity Report SOP

Investigate Identify Root cause

Determine Effectiveness of Implemented Actions Identify Actions

Implement Actions

Approved identified Actions Verify identified Actions (e.g.

Need for change control, revalidation)

Figure 2

The summary of the main / critical deviation management steps is as follows., , , , , ,

,

Description of deviation immediate action (correction) effectiveness of immediate action

separation of product manufacturing series analysis of root causes corrective / preventive action

Effectiveness of corrective action conclusion

3-Documentation of deviation / non-compliance

 Deviations must be reported in real time and notified to the quality assurance unit in a timely
manner and within a maximum of 24 hours.
 A thorough investigation of the root cause should be performed and documented.

 The investigation should be done in a timely manner and within 30 days.

 If necessary (major and critical deviations) Corrective and critical measures should be started
as soon as possible and their completion be recorded. CAPA request should be submitted to
the quality assurance department within 2 days.
 Identify and record the series of involved batch numbers that have been liberated or rejected.

1-3- All deviations should be reported as soon as they are observed. If any deviation is observed,
immediately inform the person in charge / manager of the department. While taking immediate action to
eliminate it, record its details in the deviation / non-compliance report.

The first part of the deviation / non-conformity report record sheet must be completed by the person
observing the deviation .This part includes the reporting section, date of occurrence, reporting date, type
of deviation including planned or unplanned, scope of deviation / non-compliance, description of deviation
/ non-compliance, immediate action, causes of deviation / non-compliance and proposed corrections and
paragraph need to be changed.

2-3- In determining the type of deviation, determine the planned and unplanned according to the
following definitions:
Deviation/Nonconformity Report SOP

Planned deviations: These are deviations that are pre-defined and confirmed and cover a certain
period of time or a certain number of batch numbers.These types of deviations must be approved
before implementation and should be done through the quality assurance department approved
changes control method.
Unplanned deviations: Deviations that occur as an out-of-control event that can occur at any stage of
production, packaging, testing, maintenance and storage of a pharmaceutical product.

3-3- In the section describing the deviation explain the correct and usual process of work and
deviation occurred from the correct process.
3-4 - If there is any evidence of deviation, you must attach it to the report record sheet.
3-5 - In the immediate action section, you must describe the action taken to eliminate the deviation
and the evidence for implementing that.

Examples of immediate corrections

.Products
- Quarantine
- separation
- Obliteration
• Equipment
- Deletion from the service
- Replacing
• processes
- Suspending production
-Stopping the recovery process

6-3-It should be specified if the actions taken require a change in work or instructions.
7-3-The department manager must study the reported deviation and review and approve the
immediate action taken and send it to the quality assurance department.
8-3-The quality assurance expert should study the report received and, after evaluation, identify the
type of deviation / non-compliance and classify the deviation / non-compliance. For this purpose, the
review of critical deviations up to 2 days, major deviations up to 4 days and minor deviations up to 1
week after receiving the report should be completed and closed by the quality assurance department.
About major and critical deviations should be investigated, finding root causes and implementing
preventive corrective measures should be carried out.
For Investigation, the following should be considered:
 .How and why the deviation has occurred?
. What were the conditions like at the time of the deviation?
.What products, processes or people were involved?
 Collecting data to help determining the root cause and implementing remedial action, which may
include:
- Talking to employees, suppliers and ...
-Browsing protocols, methods, forms and ......
-Checking relevant records
If the deviation is related to the critical stages of the process, its effect or potential effect on the quality
of the affected batch numbers should be investigated.

Deviations from approved calibration standards in critical instruments should be investigated and determine
whether these deviations have an impact on the quality of the intermediate materials or APIs (s) produced
using these equipment.
The real purpose of deviation research is to:
Determine the root cause of the "deviation"
Deviation/Nonconformity Report SOP

Appropriate and meaningful corrective actions should be taken

The involved system should be evaluated (e.g., training on repetition of a deviation)

10-3-After confirming the deviation report, the inspection expert must determine the reported deviation
number according to the Dev-YY-AAA format and register it in the deviation / non-compliance report (QAR-
034-1) and deviation / non-compliance logbook (QAR-034-3).
11-3-In this issue, Dev stands for Deviation, YY represents the last two digits of the solar year receiving the
report, and AAA the batch number of the report in the same year, starting with 001.
 12-3-For deviations reported outside Tekzima Pharmaceutical Company and during distribution and
maintenance in medical centers, deviation report according to the Dev-PM-YY-AAA format, determine the
reported deviation number and record in the deviation report after distribution QAR-034-2-00 record sheet.
In this issue, Dev-PM stands for Deviation Post Marketing, YY, represents the last two digits of the reporting
solar year, and the AAA report batch number for the same year, starting with 001.

Reporting
Completion of the deviation / non-compliance report record sheet and approval of the department manager
In case of any deviation from the instructions, record the cases in the QAR-034-1 record sheet and report
them to the department manager.
Related documents
corrective / preventive action record sheet CAPA (QAR-035-1)

The attachment

Appendix 1) Deviation classification diagram

Deviation / Nonconformity Report record sheet (QAR-034-1)

Post-Distribution Report record sheet (QAR-034-2)

Deviation / Non-Compliance logbook (QAR-034-3)

Recourses and references

1-Internal resources

2-WHO-Deviation Handling and Quality Risk management

Revision number Date Changes

00 /07/032017 Creating a document
01 /06/292020 Adding the revision date
Deviation/Nonconformity Report SOP

Adding the paragraph of

references and resources and
the main record sheet of the
02 /12/272020 document to the attachment
paragraph. Adding paragraphs 1
to 3, adding a description of the
deviation management process
Completion and modification of
the responsibilities paragraph,
definition and procedure,
03 /11/232021
Review of deviation / non-
compliance report record sheet
(QAR-034-1)

Appendix 1) Deviation classification diagram