InstantGMP Compliance Series

Managing Deviations for Improved Compliance

Electronic cGMP Manufacturing Execution System

Deviations

• Triggered by any unanticipated occurrence could result in adulteration

• Must be noted in batch record• Quality must conduct a material review• Then make a disposition decision• May not reprocess a batch that deviates unless

approved by Quality

Electronic cGMP Manufacturing Execution System

Problems with Deviations

• Warning letters issued to firms who failed to record and resolve production deviations

• One firm used ingredients other than the ones specified

• Another firm did not conduct an investigation of retested samples that failed specifications

• A firm claimed to have established deviation procedures, but provide no documentation

Electronic cGMP Manufacturing Execution System

Why Managing Deviations Is Important

• Intention is to make uniform, high quality products• Deviations may indicate product is not under control• May indicate that master formula may need updating

based on variations in raw materials or dietary ingredients• Quality needs to review and disposition each deviation• Lets an independent quality group make sure product that

reaches the market is free from defects

Electronic cGMP Manufacturing Execution System

Definitions

• OOS – Out of Specification• CAPA – Corrective and Preventive Action• Corrective Action – eliminate cause of an

existing undesirable situation in order to prevent a recurrence

• Preventive Action – eliminate the cause of a potential undesirable situation in order to prevent an occurrence

Electronic cGMP Manufacturing Execution System

Out of Specification

• OOS - any value that does not meet the acceptance criteria of a specification

• Triggers an investigation plan• Initial phase - the laboratory results are challenged by

retesting and comparing to a retain sample to • Second phase - investigation of the manufacturing

processes • Quality must make a disposition decision and decide

whether the batch is OK or should be rejected

Electronic cGMP Manufacturing Execution System

Investigations

• Investigations may be initiated due to:– Confirmed Out-Of-Specification (OOS) results– Out-of-Trend (OOT) - atypical results that deviate

from expected or historical data, but still meets specifications

– Failure of a component, excipient or in-process test– Unplanned disruption in production – Unplanned deviations from approved procedures,

methods or specifications

Electronic cGMP Manufacturing Execution System

Corrective and Preventative Actions

• CAPA log needed for recording deviations• Identify the specific deviation or unanticipated

occurrence• Describe the investigation• Evaluate whether or not the deviation resulted

from or could lead to a failure• Identify actions to correct and prevent a recurrence

Electronic cGMP Manufacturing Execution System

Determine the Scope

• Scope includes:– time frames during which the problem occurred– number of times the problem occurred– the number and identity of products or materials

involved– locations (including vendors) involved.

• Determine the relevant events leading up to and surrounding the event. Determine what happened, how it happened, and who, when and where.

• Clearly define the problem

Electronic cGMP Manufacturing Execution System

Determine Root Causes

• Determine possible and probable causes of the problem• Determines why the problem occurred• Root causes will typically fall into one of three categories:

– System design: Are procedures sufficient? Are other process components sufficient (materials, equipment, facilities, personnel).

– System implementation: What does, or can management do to ensure that procedures are followed?

– Performance: Is this an individual performance issue?

Electronic cGMP Manufacturing Execution System

Determine Corrective/Preventive Actions

• Use various tools and techniques, such as brainstorming, cause and effect analysis and statistical tools

• Involve people closest to the problem• Select the most effective or cost effective

corrective/preventive action• Document justifications

Electronic cGMP Manufacturing Execution System

Develop CAPA Plans

• Redesign systems and processes• Implement remedial training is needed, • Assure that there is no further performance of

the task until the necessary re-training is complete

• Set target dates and assign individuals responsible for implementation

• Use measurable outcomes to evaluate the effectiveness of the preventive actions

Record Deviations in Batch Records

Electronic cGMP Manufacturing Execution System

Benefits of Electronic Manufacturing

• More efficient than manual systems• Shrink or eliminate redundant processes and forms• Trim time and overhead costs• Reduce errors, omissions and deviations• Provide opportunities to reorganize and update

processes• Increases throughput, quality and margins

InstantGMP™

Find more videos on GMP Manufacturing in the Resource

Center at www.instantgmp.com