DEVIATION MANAGEMENT

As part of quality management system (QMS), Deviation handling plays vital role in assuring quality of products and by contributing to continuous improvement.

Deviation is an undesirable event in the pharmaceutical manufacturing process that can affect product quality or contradict/omit requirements contemplated in the approved procedures.

Deviation categorizations:

1. Incidents
2. Minor Deviations
3. Major Deviations
4. Critical deviations

Incidents:

Incidents are undesirable events that have no effect on product quality and/or do not deviate requirements contemplated in an established standards.

Record the incidents in respective documents like batch records, log books, analytical data sheets as appropriate. It nevertheless need to be documented as separate QMS events.

Possible examples of Incidents as follows:

• Temporary power failure in a warehouse where no temperature sensitive materials are stored, with no temperature excursion from the established range.

• Production process parameters or environmental monitoring data reach alert levels but are still within acceptable range.

Minor Deviations:

Minor deviations are undesirable events that have no effect on product quality but deviated contemplated requirements from established standards.

Minor deviations treated as such by applicable procedure.

Possible examples of minor deviations are given below: -

• Skip of FEFO (first expired-first out) and/ or FIFO (First in First out) principle in raw material handling.
• Balance out of tolerance used to determine gross weight of raw materials upon reception.
• Pressure differential out of established limits in class D washing area.
• Inadequately trained personnel to perform warehouse cleaning activities

Minor deviations requires documented objective evidence written in concise and clear way stating locations, person found the deviation and deviation details.

Minor deviations are normally addressed by Corrections after approval by QA which are taken to correct and contain the problem (including immediate actions), based on sufficient documented evidence.

Minor deviations do not necessarily require an investigation aimed at identifying the root causes of the problem as major and critical deviations do

Major Deviations:

Major deviations are undesirable events that effects product quality and impact to patient is unlikely and deviated contemplated requirements from established standards.

Major deviations requiring immediate action, investigation, and documented as such by the appropriate SOP

Possible examples of major deviations are given below: -

1. Use of unapproved reference standard to test an API or drug product.
2. Inadequately trained personnel to perform sterility tests.
3.  Production started without line clearance.
4. Wrong calculation of assay values during raw material dispensing
5.  Failure to load or withdraw or analyses stability samples with in schedules.
6.  Filter integrity test has been carried out using equipment with no documented installation qualification completed.
7.  Gross misbehavior of staff in a critical aseptic process.
8. Pressure differential out of established limits in aseptic fill areas.
9. Operational parameter out of range for a parameter defined as non-critical.
10. Untrained personnel responsible for segregating the approved and rejected raw material in the warehouse.
11. Failure to calibrate / preventive maintenance of instruments or equipment’s in stipulated schedules

Critical Deviations:

Critical deviations are undesirable events that effects product quality and impact to patient is highly probable including life threatening situations and deviated contemplated requirements from established standards.

Critical deviations requiring immediate action, investigation, and documented as such by the appropriate SOP

Possible examples of major deviations  are given below: -

1. Expired or rejected API component used.
2. Sterilization record of product-contact material used in aseptic filling process not available or unacceptable.
3. Incomplete inactivation stage of fermentation
4. Temperature out of control limit during detoxification stage.
5. Product mix-up
6. Breakdown of equipment during critical operations

Major or critical deviations usually require an enhanced, thorough and objective description which needs to be documented. An adequate description associated to the deviation is essential in order to perform a meaningful investigation.

Major or critical deviations would be typically first addressed by corrections, which would need QA approval as mentioned above. An investigation is then initiated on the root causes of the deviation, followed by the corresponding corrective actions.

If a minor deviation is repeated a significant number of times, it could turn into a major deviation, and must be treated as such. The investigation of the deviation should also determine the reason why the implemented corrective actions were not successful. Based on the same rationale, repetitions of one same incident can turn it into a minor deviation

Note:

The term “planned deviation” is frequently used to describe a decision to carry out a process in a different way from which it is established in a SOP, Method or Manufacturing Batch Record (e.g., a reprocess) due to an unforeseen event. Planned deviations need to be fully documented and justified. Usually, planned deviations associated to onetime events, and change control to permanent changes.